Bio

Clinical Focus


  • Psychiatry
  • Geriatric Psychiatry

Administrative Appointments


  • Associate Chief of Staff for Mental Health, VA Palo Alto Health Care System (2002 - Present)

Honors & Awards


  • Distinguished Scientist Award, American Association for Geriatric Psychiatry (2009)
  • Weinberg Award for Excellence in Geriatric Psychiatry, American Psychiatric Association (1993)

Professional Education


  • Medical Education:Stanford University School of Medicine (1974) CA
  • Residency:Stanford University School of Medicine (1978) CA
  • Internship:UCI School of Medicine (1975) CA
  • Board Certification: Geriatric Psychiatry, American Board of Psychiatry and Neurology (1991)
  • Board Certification: Psychiatry, American Board of Psychiatry and Neurology (1981)
  • BA, Yale (1971)
  • MD, Stanford (1974)

Research & Scholarship

Current Research and Scholarly Interests


Please see my home page for full descriptions of research: www.stanford.edu/people/yesavage

Clinical Trials


  • Memory and Mental Health in Aging Not Recruiting

    This study will evaluate the effectiveness of donepezil (Aricept®) and cognitive training in improving memory performance in elderly adults.

    Stanford is currently not accepting patients for this trial. For more information, please contact Leah Friedman, (650) 493 - 5000.

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  • Modafinil Treatment for Sleep/Wake Disturbances in Older Adults Not Recruiting

    Modafinil, trade named Provigil, is a medication approved by the Food and Drug Administration for the treatment of narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift work sleep disorder. Each of these problems is characterized by difficulty sleeping at night and excessive daytime sleepiness. Modafinil is prescribed during the day to counteract this sleepiness. The idea behind this treatment is that sleepiness that leads to napping during the day prevents a patient from being tired or sleepy enough to get good sleep at night. This study is designed to determine if the medication can "reset" participants' sleep/wake rhythm to a more normal rhythm.

    Stanford is currently not accepting patients for this trial. For more information, please contact Ban Ku, (650) 849 - 1971.

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  • Alzheimer's Disease Neuroimaging Initiative 2 Not Recruiting

    The purpose of this study is to build upon the information obtained in the original Alzheimer's Disease Neuroimaging Initiative (ADNI1) and ADNI-GO (Grand Opportunity; a study funded through an NIH grant under the American Recovery and Reinvestment Act), to examine how brain imaging technology can be used with other tests to measure the progression of mild cognitive impairment (MCI) and early Alzheimer's disease (AD). ADNI2 seeks to inform the neuroscience of AD. This information will aid in the early detection of AD, and in measuring the effectiveness of treatments in future clinical trials.

    Stanford is currently not accepting patients for this trial. For more information, please contact Michelle Farrell, 650-849-0491.

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  • Light Treatment for Sleep/Wake Disturbances in Alzheimer's Disease Not Recruiting

    The aim of this study is to demonstrate the efficacy of timed exposure to bright light for the treatment of disturbed nighttime sleep and daytime wake in community-dwelling dementia patients and their caregivers, and to determine if there are genetic relationships between memory problems and sleep problems

    Stanford is currently not accepting patients for this trial. For more information, please contact Leah Friedman, (650) 493 - 5000.

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  • The Effect of Memantine on Brain Structure and Chemistry in Alzheimer's Disease Patients Not Recruiting

    The aim of the proposed study is to determine if the NMDA receptor antagonist memantine has a neuroprotective effect on magnetic resonance spectroscopic imaging (MRS) measures of brain NAA and magnetic resonance imaging (MRI) volumetric measures of hippocampal volume. In secondary analyses, we will determine if measures of clinical stabilization produced by memantine in the treatment of Alzheimer's disease (AD) parallels stabilization of MRS measures of brain NAA and MRI volumetric measures of hippocampal volume.

    Stanford is currently not accepting patients for this trial. For more information, please contact Tamara Beale, (650) 852 - 3234.

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  • Age-related Longitudinal Changes in Aviator Performance Recruiting

    Our overall goal has been twofold: 1) to evaluate whether there are significant age-related changes in flight simulator performance near age 60, and 2) to assess whether there is an alternative model that can explain longitudinal flight simulator performance on the basis of measures of cognitive function and expertise.

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Teaching

2013-14 Courses


Publications

Journal Articles


  • Intraindividual variability in basic reaction time predicts middle-aged and older pilots' flight simulator performance. journals of gerontology. Series B, Psychological sciences and social sciences Kennedy, Q., Taylor, J., Heraldez, D., Noda, A., Lazzeroni, L. C., Yesavage, J. 2013; 68 (4): 487-494

    Abstract

    ObjectivesIntraindividual variability (IIV) is negatively associated with cognitive test performance and is positively associated with age and some neurological disorders. We aimed to extend these findings to a real-world task, flight simulator performance. We hypothesized that IIV predicts poorer initial flight performance and increased rate of decline in performance among middle-aged and older pilots.MethodTwo-hundred and thirty-six pilots (40-69 years) completed annual assessments comprising a cognitive battery and two 75-min simulated flights in a flight simulator. Basic and complex IIV composite variables were created from measures of basic reaction time and shifting and divided attention tasks. Flight simulator performance was characterized by an overall summary score and scores on communication, emergencies, approach, and traffic avoidance components. RESULTS: Although basic IIV did not predict rate of decline in flight performance, it had a negative association with initial performance for most flight measures. After taking into account processing speed, basic IIV explained an additional 8%-12% of the negative age effect on initial flight performance.DiscussionIIV plays an important role in real-world tasks and is another aspect of cognition that underlies age-related differences in cognitive performance.

    View details for DOI 10.1093/geronb/gbs090

    View details for PubMedID 23052365

  • Phenotyping apathy in individuals with Alzheimer disease using functional principal component analysis. American journal of geriatric psychiatry Zeitzer, J. M., David, R., Friedman, L., Mulin, E., Garcia, R., Wang, J., Yesavage, J. A., Robert, P. H., Shannon, W. 2013; 21 (4): 391-397

    Abstract

    To determine if there is a specific pattern of gross motor activity associated with apathy in individuals with Alzheimer disease (AD).Examination of ad libitum 24-hour ambulatory gross motor activity patterns.Community-dwelling, outpatient.Ninety-two individuals with AD, 35 of whom had apathy.Wrist actigraphy data were collected and examined using functional principal component analysis (fPCA).Individuals with apathy have a different pattern of gross motor activity than those without apathy (first fPCA component, p <0.0001, t = 5.73, df = 90, t test) such that there is a pronounced decline in early afternoon activity in those with apathy. This change in activity is independent of depression (p = 0.68, F[1, 89] = 0.05, analysis of variance). The decline in activity is consistent with an increase in napping. Those with apathy also have an early wake and bedtime (second fPCA component, t = 2.53, df = 90, p <0.05, t test).There is a signature activity pattern in individuals with apathy and AD that is distinct from those without apathy and those with depression. Actigraphy may be a useful adjunctive measurement in the clinical diagnosis of apathy in the context of AD.

    View details for DOI 10.1016/j.jagp.2012.12.012

    View details for PubMedID 23498386

  • Nocturia Compounds Nocturnal Wakefulness in Older Individuals with Insomnia JOURNAL OF CLINICAL SLEEP MEDICINE Zeitzer, J. M., Bliwise, D. L., Hernandez, B., Friedman, L., Yesavage, J. A. 2013; 9 (3): 259-262

    Abstract

    To determine the impact of nocturia on objective measures of sleep in older individuals with insomnia.The sleep and toileting patterns of a group of community-dwelling older men (n = 55, aged 64.3 ± 7.52 years) and women (n = 92, aged 62.5 ± 6.73 years) with insomnia were studied for two weeks using sleep logs and one week using actigraphy. The relationships between nocturia and various sleep parameters were analyzed with ANOVA and linear regression.More than half (54.2% ± 39.9%) of all log-reported nocturnal awakenings were associated with nocturia. A greater number of trips to the toilet was associated with worse log-reported restedness (p < 0.01) and sleep efficiency (p < 0.001), as well as increases in actigraph-derived measures of the number and length of nocturnal wake bouts (p < 0.001) and wake after sleep onset (p < 0.001). Actigraph-determined wake bouts were 11.5% ± 23.5% longer on nights on which there was a trip to the toilet and wake after sleep onset was 20.8% ± 33.0% longer during these nights.Nocturia is a common occurrence in older individuals with insomnia and is significantly associated with increased nocturnal wakefulness and decreased subjective restedness after sleep.

    View details for DOI 10.5664/jcsm.2492

    View details for Web of Science ID 000316209800010

    View details for PubMedID 23493881

  • Pilot Expertise and Hippocampal Size: Associations with Longitudinal Flight Simulator Performance AVIATION SPACE AND ENVIRONMENTAL MEDICINE Adamson, M. M., Bayley, P. J., Scanlon, B. K., Farrell, M. E., Hernandez, B., Weiner, M. W., Yesavage, J. A., Taylor, J. L. 2012; 83 (9): 850-857

    Abstract

    Previous research suggests that the size of the hippocampus can vary in response to intensive training (e.g., during the acquisition of expert knowledge). However, the role of the hippocampus in maintenance of skilled performance is not well understood. The Stanford/Veterans Affairs Aviation MRI Study offers a unique opportunity to observe the interaction of brain structure and multiple levels of expertise on longitudinal flight simulator performance.The current study examined the relationship between hippocampal volume and three levels of aviation expertise, defined by pilot proficiency ratings issued by the U.S. Federal Aviation Administration (11). At 3 annual time points, 60 pilots who varied in their level of aviation expertise (ages ranging from 45 to 69 yr) were tested.At baseline, higher expertise was associated with better flight simulator performance, but not with hippocampal volume. Longitudinally, there was an Expertise x Hippocampal volume interaction, in the direction that a larger hippocampus was associated with better performance at higher levels of expertise.These results are consistent with the notion that expertise in a cognitively demanding domain involves the interplay of acquired knowledge ('mental schemas') and basic hippocampal-dependent processes.

    View details for DOI 10.3357/ASEM.3215.2012

    View details for Web of Science ID 000307919100002

    View details for PubMedID 22946348

  • Decreased Daytime Motor Activity Associated With Apathy in Alzheimer Disease: An Actigraphic Study AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY David, R., Mulin, E., Friedman, L., Le Duff, F., Cygankiewicz, E., Deschaux, O., Garcia, R., Yesavage, J. A., Robert, P. H., Zeitzer, J. M. 2012; 20 (9): 806-814

    Abstract

    Across all stages of Alzheimer disease (AD), apathy is the most common neuropsychiatric symptom. Studies using the Neuropsychiatric Inventory (NPI) have found that apathy is present in up to 70% of individuals with Alzheimer disease. One of the main difficulties in assessing apathy and other neuropsychiatric symptoms is the absence of reliable, objective measures. Motor activity assessment using ambulatory actigraphy could provide an indirect, objective evaluation of apathy. The aim of our study was to assess the relationship between apathy and daytime motor activity in AD, using ambulatory actigraphy.One hundred seven AD outpatients wore a wrist actigraph (Motionlogger) during seven consecutive 24-hour periods to evaluate motor activity. Participants were divided into two subgroups according to their apathy subscores on the NPI: individuals with apathy (NPI-apathy subscores >4) and those without. Daytime mean motor activity scores were compared between the two subgroups.Individuals with AD who had symptoms of apathy (n = 43; age = 79 ± 4.7 years; Mini-Mental State Examination = 20.9 ± 4.8) had significantly lower daytime mean motor activity than AD patients without apathy (n = 64; age = 76.3 ± 7.7; Mini-Mental State Examination = 21.5 ± 4.7), while nighttime mean motor activity did not significantly differ between the two subgroups.Ambulatory actigraphy could be added to currently used questionnaires as a simple, objective technique for assessing apathy in the routine assessment of AD patients.

    View details for DOI 10.1097/JGP.0b013e31823038af

    View details for Web of Science ID 000308078500010

    View details for PubMedID 21997602

  • Periodic leg movements in sleep in elderly patients with Parkinsonism and Alzheimer's disease EUROPEAN JOURNAL OF NEUROLOGY Bliwise, D. L., Trotti, L. M., Yesavage, J. A., Rye, D. B. 2012; 19 (6): 918-923

    Abstract

    Periodic leg movements in sleep (PLMS) are non-epileptiform, repetitive movements of the lower limbs that have been associated with apparent dopamine deficiency. We hypothesized that elderly patients with a disease characterized primarily by dopamine depletion (Parkinsonism) would have higher rates of PLMS than age-matched controls or a different neurodegenerative condition not primarily involving a hypodopaminergic state, Alzheimer's disease (AD).? We compared rates of PLMS derived from in-laboratory overnight polysomnography in patients with Parkinsonism (n = 79), AD (n = 28), and non-neurologically impaired, community-based controls (n = 187).? Patients with Parkinsonism not receiving levodopa had significantly higher rates of PLMS than did patients with Parkinsonism receiving levodopa as well as higher rates than seen in AD and controls. Other medications did not appear to exert the pronounced effect of levodopa on PLMS in this Parkinsonian patient population. The symptom of leg kicking was reported more frequently in Parkinsonism and was associated with higher rates of PLMS. Caregiver reported leg kicking was unrelated to PLMS in AD.?Results are broadly compatible with a dopaminergic hypothesis for PLMS in Parkinsonism. The clinical significance of the negative findings in patients with AD requires further investigation.

    View details for DOI 10.1111/j.1468-1331.2012.03673.x

    View details for Web of Science ID 000303911600024

    View details for PubMedID 22340757

  • Brief morning light treatment for sleep/wake disturbances in older memory-impaired individuals and their caregivers SLEEP MEDICINE Friedman, L., Spira, A. P., Hernandez, B., Mather, C., Sheikh, J., Ancoli-Israel, S., Yesavage, J. A., Zeitzer, J. M. 2012; 13 (5): 546-549

    Abstract

    Scheduled exposure to bright light (phototherapy) has been used, with varying degrees of success, to treat sleep disruption in older individuals. Most of these studies have been done in institutional settings and have used several hours of daily light exposure. Such a regimen in the home setting may be untenable, especially when the individual with the sleep disruption has memory impairment and is being cared for by a family member. As such, we examined the effectiveness of a "user-friendly" phototherapy protocol that would be readily usable in the home environment.We exposed a group of 54 older caregiver/care recipient dyads, in which the care recipient had memory impairment, to two weeks of morning bright light phototherapy. Dyads were exposed to either bright white (?4200 lux) or dim red (?90 lux) light for 30 min every day, starting within 30 min of rising. All subjects also received sleep hygiene therapy. Objective (actigraphy) and subjective measures of sleep and mood were obtained at baseline and at the end of the two weeks of phototherapy.In care recipients, actigraphy- and log-determined time in bed and total sleep time declined in the active condition (p<0.05, ANOVA); there was no corresponding change in subjective insomnia symptoms (p's>0.37, ANOVA). The decrease in the time in bed was associated with an earlier out of bed time in the morning (p<0.001, Pearson correlation). The decrease in the total sleep time was associated with a decrease in sleep efficiency (p<0.001, Pearson correlation) and an increase in wake after sleep onset (p<0.001, Pearson correlation). In caregivers, there were no differential changes in actigraphic measures of sleep (p's>0.05, ANOVA). Actigraphy-measured wake after sleep onset and sleep efficiency did, however, improve in both conditions, as did sleepiness, insomnia symptoms, and depressive symptomatology (p's<0.05, ANOVA).Exposure to this regimen of phototherapy diminished sleep in older individuals with memory impairments. Their caregivers, however, experienced an improvement in sleep and mood that appeared independent of the phototherapy and likely due to participation in this protocol or the sleep hygiene therapy.

    View details for DOI 10.1016/j.sleep.2011.11.013

    View details for Web of Science ID 000303346800016

    View details for PubMedID 22406033

  • Sleep-Disordered Breathing in Vietnam Veterans with Posttraumatic Stress Disorder AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Yesavage, J. A., Kinoshita, L. M., Kimball, T., Zeitzer, J., Friedman, L., Noda, A., David, R., Hernandez, B., Lee, T., Cheng, J., O'Hara, R. 2012; 20 (3): 199-204

    Abstract

    : To study the prevalence of sleep-disordered breathing (SDB) in Vietnam- era veterans.: This was an observational study of Vietnam-era veterans using unattended, overnight polysomnography, cognitive testing, and genetic measures.: A sample of 105 Vietnam-era veterans with posttraumatic stress disorder: 69% had an Apnea Hypopnea Index >10. Their mean body mass index was 31, "obese" by Centers for Disease Control and Prevention criteria, and body mass index was significantly associated with Apnea Hypopnea Index (Spearman r = 0.41, N = 97, p < 0.0001). No significant effects of sleep-disordered breathing or apolipoprotein status were found on an extensive battery of cognitive tests.: There is a relatively high prevalence of SDB in these patients which raises the question of to what degree excess cognitive loss in older PTSD patients may be due to a high prevalence of SDB.

    View details for DOI 10.1097/JGP.0b013e3181e446ea

    View details for Web of Science ID 000300642300002

    View details for PubMedID 20808112

  • Phenotyping Apathy in Individuals With Alzheimer Disease Using Functional Principal Component Analysis. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry Zeitzer, J. M., David, R., Friedman, L., Mulin, E., Garcia, R., Wang, J., Yesavage, J. A., Robert, P. H., Shannon, W. 2012

    Abstract

    OBJECTIVES:: To determine if there is a specific pattern of gross motor activity associated with apathy in individuals with Alzheimer disease (AD). DESIGN:: Examination of ad libitum 24-hour ambulatory gross motor activity patterns. SETTING:: Community-dwelling, outpatient. PARTICIPANTS:: Ninety-two individuals with AD, 35 of whom had apathy. MEASUREMENTS:: Wrist actigraphy data were collected and examined using functional principal component analysis (fPCA). RESULTS:: Individuals with apathy have a different pattern of gross motor activity than those without apathy (first fPCA component, p <0.0001, t = 5.73, df = 90, t test) such that there is a pronounced decline in early afternoon activity in those with apathy. This change in activity is independent of depression (p = 0.68, F[1, 89] = 0.05, analysis of variance). The decline in activity is consistent with an increase in napping. Those with apathy also have an early wake and bedtime (second fPCA component, t = 2.53, df = 90, p <0.05, t test). CONCLUSIONS:: There is a signature activity pattern in individuals with apathy and AD that is distinct from those without apathy and those with depression. Actigraphy may be a useful adjunctive measurement in the clinical diagnosis of apathy in the context of AD.

    View details for PubMedID 22367164

  • Delineating a Retesting Zone Using Receiver Operating Characteristic Analysis on Serial QuantiFERON Tuberculosis Test Results in US Healthcare Workers. Pulmonary medicine Thanassi, W., Noda, A., Hernandez, B., Newell, J., Terpeluk, P., Marder, D., Yesavage, J. A. 2012; 2012: 291294-?

    Abstract

    Objective. To find a statistically significant separation point for the QuantiFERON Gold In-Tube (QFT) interferon gamma release assay that could define an optimal "retesting zone" for use in serially tested low-risk populations who have test "reversions" from initially positive to subsequently negative results. Method. Using receiver operating characteristic analysis (ROC) to analyze retrospective data collected from 3 major hospitals, we searched for predictors of reversion until statistically significant separation points were revealed. A confirmatory regression analysis was performed on an additional sample. Results. In 575 initially positive US healthcare workers (HCWs), 300 (52.2%) had reversions, while 275 (47.8%) had two sequential positive tests. The most statistically significant (Kappa?=?0.48, chi-square?=?131.0, P < 0.001) separation point identified by the ROC for predicting reversion was the tuberculosis antigen minus-nil (TBag-nil) value at 1.11 International Units per milliliter (IU/mL). The second separation point was found at TBag-nil at 0.72?IU/mL (Kappa?=?0.16, chi-square?=?8.2, P < 0.01). The model was validated by the regression analysis of 287?HCWs. Conclusion. Reversion likelihood increases as the TBag-nil approaches the manufacturer's cut-point of 0.35?IU/mL. The most statistically significant separation point between those who test repeatedly positive and those who revert is 1.11?IU/mL. Clinicians should retest low-risk individuals with initial QFT results?

    View details for DOI 10.1155/2012/291294

    View details for PubMedID 23326660

  • Effectiveness of evening phototherapy for insomnia is reduced by bright daytime light exposure SLEEP MEDICINE Zeitzer, J. M., Friedman, L., Yesavage, J. A. 2011; 12 (8): 805-807

    Abstract

    To examine the effect of ambulatory daytime light exposure on phase delays and on the advances produced by timed exposure to bright evening or morning light.As a subset of a larger study, 32 older (63.0 ± 6.43 years) adults with primary insomnia were randomized to an at-home, single-blind, 12-week, parallel-group study entailing daily exposure to 45 min of scheduled evening or morning bright (?4000 lux) light. Light exposure patterns during the baseline and the last week of treatment were monitored using actigraphs with built-in illuminance detectors. Circadian phase was determined through analysis of in-laboratory collected plasma melatonin.Less daytime light exposure during the last week of treatment was significantly associated with larger phase delays in response to evening light (r's>0.78). Less daytime light exposure during the last week of treatment was also associated with a significant delay in wake time (r's>-0.75). There were no such relationships between light exposure history and phase advances in response to morning light.Greater light exposure during the daytime may decrease the ability of evening light, but not morning light, exposure to engender meaningful changes of circadian phase.

    View details for DOI 10.1016/j.sleep.2011.02.005

    View details for Web of Science ID 000295764800013

    View details for PubMedID 21855408

  • The Roles of COMT val158met Status and Aviation Expertise in Flight Simulator Performance and Cognitive Ability BEHAVIOR GENETICS Kennedy, Q., Taylor, J. L., Noda, A., Adamson, M., Murphy, G. M., Zeitzer, J. M., Yesavage, J. A. 2011; 41 (5): 700-708

    Abstract

    The polymorphic variation in the val158met position of the catechol-O-methyltransferase (COMT) gene is associated with differences in executive performance, processing speed, and attention. The purpose of this study is: (1) replicate previous COMT val158met findings on cognitive performance; (2) determine whether COMT val158met effects extend to a real-world task, aircraft navigation performance in a flight simulator; and (3) determine if aviation expertise moderates any effect of COMT val158met status on flight simulator performance. One hundred seventy two pilots aged 41-69 years, who varied in level of aviation training and experience, completed flight simulator, cognitive, and genetic assessments. Results indicate that although no COMT effect was found for an overall measure of flight performance, a positive effect of the met allele was detected for two aspects of cognitive ability: executive functioning and working memory performance. Pilots with the met/met genotype benefited more from increased levels of expertise than other participants on a traffic avoidance measure, which is a component of flight simulator performance. These preliminary results indicate that COMT val158met polymorphic variation can affect a real-world task.

    View details for DOI 10.1007/s10519-010-9436-z

    View details for Web of Science ID 000294297200008

    View details for PubMedID 21193954

  • Initial Cognitive Performance Predicts Longitudinal Aviator Performance JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES Yesavage, J. A., Jo, B., Adamson, M. M., Kennedy, Q., Noda, A., Hernandez, B., Zeitzer, J. M., Friedman, L. F., Fairchild, K., Scanlon, B. K., Murphy, G. M., Taylor, J. L. 2011; 66 (4): 444-453

    Abstract

    The goal of the study was to improve prediction of longitudinal flight simulator performance by studying cognitive factors that may moderate the influence of chronological age.We examined age-related change in aviation performance in aircraft pilots in relation to baseline cognitive ability measures and aviation expertise. Participants were aircraft pilots (N = 276) aged 40-77.9. Flight simulator performance and cognition were tested yearly; there were an average of 4.3 (± 2.7; range 1-13) data points per participant. Each participant was classified into one of the three levels of aviation expertise based on Federal Aviation Administration pilot proficiency ratings: least, moderate, or high expertise.Addition of measures of cognitive processing speed and executive function to a model of age-related change in aviation performance significantly improved the model. Processing speed and executive function performance interacted such that the slowest rate of decline in flight simulator performance was found in aviators with the highest scores on tests of these abilities. Expertise was beneficial to pilots across the age range studied; however, expertise did not show evidence of reducing the effect of age.These data suggest that longitudinal performance on an important real-world activity can be predicted by initial assessment of relevant cognitive abilities.

    View details for DOI 10.1093/geronb/gbr031

    View details for Web of Science ID 000293251900007

    View details for PubMedID 21586627

  • Circadian Clock Gene Polymorphisms and Sleep-Wake Disturbance in Alzheimer Disease AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Yesavage, J. A., Noda, A., Hernandez, B., Friedman, L., Cheng, J. J., Tinklenberg, J. R., Hallmayer, J., O'Hara, R., David, R., Robert, P., Landsverk, E., Zeitzer, J. M. 2011; 19 (7): 635-643

    Abstract

    One of the hypothesized causes of the breakdown in sleep-wake consolidation often occurring in individuals with Alzheimer disease (AD) is the dysfunction of the circadian clock. The goal of this study is to report indices of sleep-wake function collected from individuals with AD in relation to relevant polymorphisms in circadian clock-related genes.One week of ad libitum ambulatory sleep data collection.At-home collection of sleep data and in-laboratory questionnaire.Two cohorts of AD participants. Cohort 1 (N = 124): individuals with probable AD recruited from the Stanford/Veterans Affairs, National Institute on Aging Alzheimer's Disease Core Center (N = 81), and the Memory Disorders Clinic at the University of Nice School of Medicine (N = 43). Cohort 2 (N = 176): individuals with probable AD derived from the Alzheimer's Disease Neuroimaging Initiative data set.Determination of sleep-wake state was obtained by wrist actigraphy data for 7 days in Cohort 1 and by the Neuropsychiatric Inventory questionnaire for Cohort 2. Both cohorts were genotyped by using an Illumina Beadstation (Illumina, San Diego, CA), and 122 circadian-related single-nucleotide polymorphisms (SNPs) were examined. In Cohort 1, an additional polymorphism (variable-number tandem repeat in per3) was also determined.Adjusting for multiple tests, none of the candidate gene SNPs were significantly associated with the amount of wake time after sleep onset (WASO), a marker of sleep consolidation. Although the study was powered sufficiently to identify moderate-sized correlations, we found no relationships likely to be of clinical relevance.It is unlikely that a relationship with a clinically meaningful correlation exists between the circadian rhythm-associated SNPs and WASO in individuals with AD.

    View details for DOI 10.1097/JGP.0b013e31820d92b2

    View details for Web of Science ID 000292031900005

    View details for PubMedID 21709609

  • Influences of APOE epsilon 4 and Expertise on Performance of Older Pilots PSYCHOLOGY AND AGING Taylor, J. L., Kennedy, Q., Adamson, M. M., Lazzeroni, L. C., Noda, A., Murphy, G. M., Yesavage, J. A. 2011; 26 (2): 480-487

    Abstract

    Little is known about how APOE ?4-related differences in cognitive performance translate to real-life performance, where training and experience may help to sustain performance. We investigated the influences of APOE ?4 status, expertise (FAA pilot proficiency ratings), and their interaction on longitudinal flight simulator performance. Over a 2-year period, 139 pilots aged 42-69 years were tested annually. APOE ?4 carriers had lower memory performance than noncarriers (p = .019). APOE interacted with Expertise (p = .036), such that the beneficial influence of expertise (p = .013) on longitudinal flight simulator performance was more pronounced for ?4 carriers. Results suggest that relevant training and activity may help sustain middle-aged and older adults' real-world performance, especially among APOE ?4 carriers.

    View details for DOI 10.1037/a0021697

    View details for Web of Science ID 000291668800026

    View details for PubMedID 21668123

  • Faster REM sleep EEG and worse restedness in older insomniacs with HLA DQB1*0602 PSYCHIATRY RESEARCH Zeitzer, J. M., Fisicaro, R. A., Grove, M. E., Mignot, E., Yesavage, J. A., Friedman, L. 2011; 187 (3): 397-400

    Abstract

    HLA DQB1*0602 is found in most individuals with hypocretin-deficient narcolepsy, a disorder characterized by a severe disruption of sleep and wake. Population studies indicate that DQB1*0602 may also be associated with normal phenotypic variation of rapid eye movement (REM) sleep. Disruption of REM sleep has been linked to specific symptoms of insomnia. We here examine the relationship of sleep and DQB1*0602 in older individuals (n=46) with primary insomnia, using objective (polysomnography, wrist actigraphy) and subjective (logs, scales) measures. DQB1*0602 positivity was similarly distributed in the older individuals with insomnia (24%) as in the general population (25%). Most sleep variables were statistically indistinguishable between DQB1*0602 positive and negative subjects except that those with the allele reported that they were significantly less well rested than those without it. When sleep efficiencies were lower than 70%, DQB1*0602 positive subjects reported being less well rested at the same sleep efficiency than those without the allele. Examination of EEG during REM sleep also revealed that DQB1*0602 positive subjects had EEG shifted towards faster frequencies compared with negative subjects. Thus, DQB1*0602 positivity is associated with both a shift in EEG power spectrum to faster frequencies during REM sleep and a diminution of restedness given the same sleep quantity.

    View details for DOI 10.1016/j.psychres.2011.01.007

    View details for Web of Science ID 000290506500014

    View details for PubMedID 21292329

  • Lack of Association Between COMT Polymorphisms and Apathy in Alzheimer's Disease JOURNAL OF ALZHEIMERS DISEASE David, R., Friedman, L., Mulin, E., Noda, A., Le Duff, F., Kennedy, Q., Garcia, R., Robert, P. H., Yesavage, J. A., Zeitzer, J. M. 2011; 27 (1): 155-161

    Abstract

    We tested the hypothesis that single nucleotide polymorphisms (SNPs) in catechol-O-methyltransferase (COMT) are associated with apathy in individuals with Alzheimer's disease (AD). We analyzed a cohort of 105 Caucasian individuals with AD (age = 79.3 ± 7.03 years; MMSE = 20.2 ± 4.4) according to the presence of apathy, as defined either by the Neuropsychiatric Inventory or the Apathy Inventory. Polymorphisms in seventeen SNPs in COMT were examined. A replication cohort consisting of 176 Caucasian AD subjects in the ADNI database was also analyzed. None of the candidate gene SNPs were significantly associated with the presence of apathy in either cohort. We did not find any SNPs in COMT that were consistently associated with apathy in individuals with AD.

    View details for DOI 10.3233/JAD-2011-110491

    View details for Web of Science ID 000296570400014

    View details for PubMedID 21785189

  • MR Spectroscopy for Assessment of Memantine Treatment in Mild to Moderate Alzheimer Dementia JOURNAL OF ALZHEIMERS DISEASE Ashford, J. W., Adamson, M., Beale, T., La, D., Hernandez, B., Noda, A., Rosen, A., O'Hara, R., Fairchild, J. K., Spielman, D., Yesavage, J. A. 2011; 26: 331-336

    Abstract

    Magnetic Resonance Spectroscopy (MRS) may provide a precise and reliable assessment of the extent and severity of neural tissue loss caused by various diseases. In particular, the N-Acetyl Aspartate (NAA) and Creatine (Cr) ratio has been found to be an indicator of the degree of neuronal loss in Alzheimer's disease (AD). Memantine is thought to benefit the AD brain by stabilizing the NMDA receptors on neurons in turn reducing excitotoxicity. Despite its effectiveness in treating moderate to severe AD, memantine has not had similar success in the treatment of mildly demented AD patients. The objective of this study was to test whether memantine would slow or prevent the loss of neurons in mild to moderate AD patients.A double-blind placebo-controlled study was designed to measure the effect of a year-long course of memantine in patients with a probable AD diagnosis with mild to moderate dementia. The primary outcome measure was stipulated to be change in MRS NAA/Cr ratio in inferior parietal cortex in memantine relative to the placebo treatment condition. The secondary outcome measures were changes in cognitive and function scale scores.This pilot study failed to demonstrate a benefit of memantine on the primary outcome measure, the inferior parietal NAA/Cr ratio, or the secondary outcome measures.More studies are needed to determine the effect of memantine on regions of the brain significantly affected by AD pathology.

    View details for DOI 10.3233/JAD-2011-0021

    View details for Web of Science ID 000297842800025

    View details for PubMedID 21971472

  • Nicotine Deprivation and Pilot Performance During Simulated Flight AVIATION SPACE AND ENVIRONMENTAL MEDICINE Mumenthaler, M. S., Benowitz, N. L., Taylor, J. L., Friedman, L., Noda, A., Yesavage, J. A. 2010; 81 (7): 660-664

    Abstract

    Most airlines enforce no-smoking policies, potentially causing flight performance decrements in pilots who are smokers. We tested the hypotheses that nicotine withdrawal affects aircraft pilot performance within 12 h of smoking cessation and that chewing nicotine gum leads to significant relief of these withdrawal effects.There were 29 pilots, regular smokers, who were tested in a Frasca 141 flight simulator on two 13-h test days, each including three 75-min flights (0 hr, 6 hr, 12 hr) in a randomized, controlled trial. On the first day (baseline), all pilots smoked one cigarette per hour. On the second day, pilots were randomly assigned to one of four groups: (1) nicotine cigarettes; (2) nicotine gum; (3) placebo gum; (4) no cigarettes/no gum. Flight Summary Scores (FSS) were compared between groups with repeated measures ANOVAs.No statistically significant differences in overall simulator flight performance were revealed between pilots who smoked cigarettes and pilots who were not allowed to smoke cigarettes or chew nicotine gum, but there was a trend for pilots who were not allowed to smoke to perform worse. However, pilots who chewed placebo gum performed significantly worse during the 6-h (FSS = -0.03) as well as during the 12-h flight (FSS = -0.08) than pilots who chewed nicotine gum (FSS = 0.15 / 0.30, respectively).Results suggest that nicotine withdrawal effects can impair aircraft pilot performance within 12 h of smoking cessation and that during smoking abstinence chewing one stick of 4-mg nicotine gum per hour may lead to significantly better overall flight performance compared to chewing placebo gum.

    View details for DOI 10.3357/ASEM.2701.2010

    View details for Web of Science ID 000279187200006

    View details for PubMedID 20597245

  • The impact of brain size on pilot performance varies with aviation training and years of education JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY Adamson, M. M., Samarina, V., Xu XiangYan, X. Y., Huynh, V., Kennedy, Q., Weiner, M., Yesavage, J., Taylor, J. L. 2010; 16 (3): 412-423

    Abstract

    Previous studies have consistently reported age-related changes in cognitive abilities and brain structure. Previous studies also suggest compensatory roles for specialized training, skill, and years of education in the age-related decline of cognitive function. The Stanford/VA Aviation Study examines the influence of specialized training and skill level (expertise) on age-related changes in cognition and brain structure. This preliminary report examines the effect of aviation expertise, years of education, age, and brain size on flight simulator performance in pilots aged 45-68 years. Fifty-one pilots were studied with structural magnetic resonance imaging, flight simulator, and processing speed tasks. There were significant main effects of age (p < .01) and expertise (p < .01), but not of whole brain size (p > .1) or education (p > .1), on flight simulator performance. However, even though age and brain size were correlated (r = -0.41), age differences in flight simulator performance were not explained by brain size. Both aviation expertise and education were involved in an interaction with brain size in predicting flight simulator performance (p < .05). These results point to the importance of examining measures of expertise and their interactions to assess age-related cognitive changes.

    View details for DOI 10.1017/S1355617710000111

    View details for Web of Science ID 000277579000002

    View details for PubMedID 20193103

  • Age and Expertise Effects in Aviation Decision Making and Flight Control in a Flight Simulator AVIATION SPACE AND ENVIRONMENTAL MEDICINE Kennedy, Q., Taylor, J. L., Reade, G., Yesavage, J. A. 2010; 81 (5): 489-497

    Abstract

    Age (due to declines in cognitive abilities necessary for navigation) and level of aviation expertise are two factors that may affect aviation performance and decision making under adverse weather conditions. We examined the roles of age, expertise, and their relationship on aviation decision making and flight control performance during a flight simulator task.Seventy-two IFR-rated general aviators, aged 19-79 yr, made multiple approach, holding pattern entry, and landing decisions while navigating under Instrument Flight Rules weather conditions. Over three trials in which the fog level varied, subjects decided whether or not to land the aircraft. They also completed two holding pattern entries. Subjects' flight control during approaches and holding patterns was measured.Older pilots (41+ yr) were more likely than younger pilots to land when visibility was inadequate (older pilots' mean false alarm rate: 0.44 vs 0.25). They also showed less precise flight control for components of the approach, performing 0.16 SD below mean approach scores. Expertise attenuated an age-related decline in flight control during holding patterns: older IFR/CFI performed 0.73 SD below mean score; younger IFR/CFI, younger CFII/ATP, older CFII/ATP: 0.32, 0.26, 0.03 SD above mean score. Additionally, pilots with faster processing speed (by median split) had a higher mean landing decision false alarm rate (0.42 vs 0.28), yet performed 0.14 SD above the mean approach control score.Results have implications regarding specialized training for older pilots and for understanding processes involved in older adults' real world decision making and performance.

    View details for DOI 10.3357/ASEM.2684.2010

    View details for Web of Science ID 000277133500006

    View details for PubMedID 20464816

  • Increasing the Ranks of Academic Researchers in Mental Health: A Multisite Approach to Postdoctoral Fellowship Training ACADEMIC MEDICINE O'Hara, R., Cassidy-Eagle, E. L., Beaudreau, S. A., Eyler, L. T., Gray, H. L., Giese-Davis, J., Hubbard, J., Yesavage, J. A. 2010; 85 (1): 41-47

    Abstract

    This report highlights the use of multisite training for psychiatry and psychology postdoctoral fellows developing careers in academic clinical research in the field of mental health. The objective is to describe a model of training for young investigators to establish independent academic clinical research careers, including (1) program structure and eligibility, (2) program goals and development of a multisite curriculum, (3) use of technology for implementing the program across multiple sites, and (4) advantages and challenges of this multisite approach. In 2000, in collaboration with the Veterans Affairs (VA) Mental Illness Research, Education and Clinical Centers (MIRECCs), the VA Office of Academic Affiliations launched the Special Fellowship Program in Advanced Psychiatry and Psychology. Each of the 10 currently participating VA sites across the United States is affiliated with a MIRECC and an academic medical institution. In the first five years of this fellowship program, 83 fellows (34 psychiatrists and 49 psychologists) have participated. The success of this multisite approach is evidenced by the 58 fellows who have already graduated from the program: 70% have entered academic clinical research positions, and over 25 have obtained independent extramural grant support from the VA or the National Institutes of Health. Multisite training results in a greater transfer of knowledge and capitalizes on the nationwide availability of experts, creating unique networking and learning opportunities for trainees. The VA's multisite fellowship program plays a valuable role in preparing substantial numbers of psychiatry and psychology trainees for a range of academic clinical research and leadership positions in the field of mental health.

    View details for DOI 10.1097/ACM.0b013e3181c47c51

    View details for Web of Science ID 000276131300015

    View details for PubMedID 20042819

  • Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Britschgi, M., Olin, C. E., Johns, H. T., Takeda-Uchimura, Y., LeMieux, M. C., Rufibach, K., Rajadas, J., Zhang, H., Tomooka, B., Robinson, W. H., Clark, C. M., Fagan, A. M., Galasko, D. R., Holtzman, D. M., Jutel, M., Kaye, J. A., Lemere, C. A., Leszek, J., Li, G., Peskind, E. R., Quinn, J. F., Yesavage, J. A., Ghiso, J. A., Wyss-Coray, T. 2009; 106 (29): 12145-12150

    Abstract

    A number of distinct beta-amyloid (Abeta) variants or multimers have been implicated in Alzheimer's disease (AD), and antibodies recognizing such peptides are in clinical trials. Humans have natural Abeta-specific antibodies, but their diversity, abundance, and function in the general population remain largely unknown. Here, we demonstrate with peptide microarrays the presence of natural antibodies against known toxic Abeta and amyloidogenic non-Abeta species in plasma samples and cerebrospinal fluid of AD patients and healthy controls aged 21-89 years. Antibody reactivity was most prominent against oligomeric assemblies of Abeta and pyroglutamate or oxidized residues, and IgGs specific for oligomeric preparations of Abeta1-42 in particular declined with age and advancing AD. Most individuals showed unexpected antibody reactivities against peptides unique to autosomal dominant forms of dementia (mutant Abeta, ABri, ADan) and IgGs isolated from plasma of AD patients or healthy controls protected primary neurons from Abeta toxicity. Aged vervets showed similar patterns of plasma IgG antibodies against amyloid peptides, and after immunization with Abeta the monkeys developed high titers not only against Abeta peptides but also against ABri and ADan peptides. Our findings support the concept of conformation-specific, cross-reactive antibodies that may protect against amyloidogenic toxic peptides. If a therapeutic benefit of Abeta antibodies can be confirmed in AD patients, stimulating the production of such neuroprotective antibodies or passively administering them to the elderly population may provide a preventive measure toward AD.

    View details for DOI 10.1073/pnas.0904866106

    View details for Web of Science ID 000268178400059

    View details for PubMedID 19581601

  • Gene expression profile of the PDAPP mouse model for Alzheimer's disease with and without Apolipoprotein E NEUROBIOLOGY OF AGING Selwood, S. P., Parvathy, S., Cordell, B., Ryan, H. S., Oshidari, F., Vincent, V., Yesavage, J., Lazzeroni, L. C., Murphy, G. M. 2009; 30 (4): 574-590

    Abstract

    The APOE epsilon 4 allele is a strong risk factor for Alzheimer's disease (AD). However, the molecular basis for this effect remains unclear. We examined expression of approximately 12,000 genes and expressed sequence tags in the hippocampus and cortex of PDAPP (APP(V717)) mice modeling AD that show extensive amyloid beta (A beta) deposition, and in PDAPP mice lacking murine APOE expression, which show marked attenuation of A beta deposition in the brain. Wild type and APOE knockout animals were also examined. Expression levels were determined at the initial stage of A beta deposition, as well as in older animals showing extensive neuropathological changes. Fifty-four transcripts were identified using our statistical analysis as differentially regulated between the PDAPP and PDAPP/APOE ko mice, whereas 31 transcripts were classified as differentially regulated among PDAPP mice and WT animals, and seven transcripts were identified as regulated between the PDAPP/APOE ko animals and the APOE ko animals. Interestingly, many of the differentially regulated genes we detected can be related to biological processes previously shown to be important in AD pathophysiology, including inflammation, calcium homeostasis, cholesterol transport and uptake, kinases and phosphatases involved in tau phosphorylation and dephosphorylation, mitochondrial energy metabolism, protein degradation, neuronal growth, endoplasmic reticulum (ER) stress related proteins, antioxidant activity, cytoskeletal organization, and presenilin binding proteins. Regulated genes also included some not directly associated with AD in the past but likely to be involved in known AD pathophysiologic mechanisms, and others that may represent completely novel factors in the pathogenesis of AD. These results provide a global molecular profile of hippocampal and cortical gene expression during the initial and intermediate stages Abeta deposition, and the effects of APOE deletion on this process.

    View details for DOI 10.1016/j.neurobiolaging.2007.08.006

    View details for Web of Science ID 000264579500013

    View details for PubMedID 17904698

  • Acetylcholinesterase inhibitor in combination with cognitive training in older adults JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES Yesavage, J. A., Friedman, L., Ashford, J. W., Kraemer, H. C., Mumenthaler, M. S., Noda, A., Hoblyn, J. 2008; 63 (5): P288-P294

    Abstract

    To determine if donepezil, an acetylcholinesterase (AChE) inhibitor, improved the assimilation of cognitive training by older adults with memory complaints, we gave 168 nondemented, community-dwelling volunteers with memory complaints either 5 mg of donepezil (Aricept) or placebo daily for 6 weeks in a randomized, double-blind, placebo-controlled trial. The dosage rose to 10 mg daily for another 6 weeks before a 2-week course of cognitive training and was maintained for the remainder of a year. Cognitive training improved performance; donepezil was well tolerated. However, there were no significant benefits of donepezil compared with placebo. An additional dose-ranging study with a starting dose of 5 mg a day suggests that the high dose was not the reason. Physiological tolerance may occur with chronic donepezil treatment and may increase AChE levels; this may be why short-term studies have shown the benefit of AChE inhibitor use in nondemented participants whereas chronic use has failed to enhance cognition.

    View details for Web of Science ID 000259517200004

    View details for PubMedID 18818443

  • Donepezil treatment and Alzheimer disease: Can the results of Randomized clinical trials be applied to Alzheimer disease patients in clinical practice? AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Tinklenberg, J. R., Kraemer, H. C., Yaffe, K., Ross, L., Sheikh, J., Ashford, J. W., Yesavage, J. A., Taylor, J. L. 2007; 15 (11): 953-960

    Abstract

    To determine if results from randomized clinical trials of donepezil in Alzheimer disease (AD) patients can be applied to AD patients in clinical practice by comparing the findings from a Nordic one-year randomized AD donepezil trial with data from a one-year prospective, observational study of AD patients.AD patients from a consortium of California sites were systematically followed for at least one year. Their treatment regimens, including prescription of donepezil, were determined by their individual physician according to his or her usual criteria.The 148 California patients treated with donepezil had a one-year decline of 1.3 (3.5 SD) points on the Mini-Mental State Exam compared to a decline of 3.3 (4.4 SD) in the 158 AD patients who received no anti-Alzheimer drugs. The Mini-Mental State Exam decline in Nordic sample was approximately 0.25 points for the 91 patients receiving donepezil and approximately 2.2 for the 98 placebo patients. The overall effect sizes were estimated at about 0.49 in both studies. The California data were further analyzed using propensity methods; after taking into account differences that could bias prescribing decisions, benefits associated with taking donepezil remained.A comparison of a randomized clinical trial of donepezil in AD patients and this observational study indicates that if appropriate methodological and statistical precautions are undertaken, then results from randomized clinical trials can be predictive with AD patients in clinical practice. This California study supports the modest effectiveness of donepezil in AD patients having clinical characteristics similar to those of the Nordic study.

    View details for Web of Science ID 000250617800005

    View details for PubMedID 17974866

  • Should one use medications in combination with cognitive training? If so, which ones? JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES Yesavage, J., Hoblyn, J., Friedman, L., Mumenthaler, M., Schneider, B., O'Hara, R. 2007; 62: 11-18

    Abstract

    In this article, we review current research regarding diagnosis of cognitive impairment in nondemented adults and discuss why medications and cognitive training together may be more beneficial than either alone. We also review potential cognitive enhancers and future research challenges. There are major reasons for such research: (a) Large numbers of older adults without dementia but with cognitive problems are not treatable with current cognitive training techniques; (b) some medications offer a rationale (i.e., cognitive enhancement) and some evidence that they might be a useful adjunct; and (c) there are unanswered questions about which population to target, which medications to use, how to administer them, and issues regarding tolerance and use of appropriate (active) placebo controls. As the number of cognitively impaired older adults grows, it is likely that there will be pressure to treat more broadly with both medications and cognitive training.

    View details for Web of Science ID 000253836500002

    View details for PubMedID 17565161

  • In Alzheimer disease, increased wake fragmentation found in those with lower hypocretin-1 NEUROLOGY Friedman, L. F., Zeitzer, J. M., Lin, L., Hoff, D., Mignot, E., Peskind, E. R., Yesavage, J. A. 2007; 68 (10): 793-794

    View details for Web of Science ID 000244679900020

    View details for PubMedID 17339595

  • Pilot age and expertise predict flight simulator performance - A 3-year longitudinal study NEUROLOGY Taylor, J. L., Kennedy, Q., Noda, A., Yesavage, J. A. 2007; 68 (9): 648-654

    Abstract

    Expert knowledge may compensate for age-related declines in basic cognitive and sensory-motor abilities in some skill domains. We investigated the influence of age and aviation expertise (indexed by Federal Aviation Administration pilot ratings) on longitudinal flight simulator performance.Over a 3-year period, 118 general aviation pilots aged 40 to 69 years were tested annually, in which their flight performance was scored in terms of 1) executing air-traffic controller communications; 2) traffic avoidance; 3) scanning cockpit instruments; 4) executing an approach to landing; and 5) a flight summary score.More expert pilots had better flight summary scores at baseline and showed less decline over time. Secondary analyses revealed that expertise effects were most evident in the accuracy of executing aviation communications, the measure on which performance declined most sharply over time. Regarding age, even though older pilots initially performed worse than younger pilots, over time older pilots showed less decline in flight summary scores than younger pilots. Secondary analyses revealed that the oldest pilots did well over time because their traffic avoidance performance improved more vs younger pilots.These longitudinal findings support previous cross-sectional studies in aviation as well as non-aviation domains, which demonstrated the advantageous effect of prior experience and specialized expertise on older adults' skilled cognitive performances.

    View details for Web of Science ID 000244482400005

    View details for PubMedID 17325270

  • Coping, symptoms, and functioning outcomes of patients with posttraumatic stress disorder JOURNAL OF TRAUMATIC STRESS Tiet, Q. Q., Rosen, C., Cavella, S., Moos, R. H., Finney, J. W., Yesavage, J. 2006; 19 (6): 799-811

    Abstract

    This study examines the association between approach coping and better functioning outcomes and the reciprocal relationships between coping and posttraumatic stress disorder (PTSD) symptoms in patients diagnosed with PTSD. Posttraumatic stress disorder patients receiving services in five VA health care systems were randomly selected and surveyed at baseline and followed 10 months later. Analyses of longitudinal data using structural equation modeling techniques showed that more approach coping predicted better family and social functioning. Cognitive avoidance coping predicted more PTSD symptoms, and more PTSD symptoms predicted more approach coping and more behavioral avoidance coping. Approach coping may enable patients with chronic PTSD to establish and maintain better relationships with family and friends, despite continuing PTSD.

    View details for DOI 10.1002/jts.20185

    View details for Web of Science ID 000243184200005

    View details for PubMedID 17195979

  • Factors associated with psychiatric hospitalization of individuals diagnosed with dementia and comorbid bipolar disorder JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Brooks, J. O., Hoblyn, J. C., Kraemer, H. C., Yesavage, J. A. 2006; 19 (2): 72-77

    Abstract

    The objective was to determine risk factors of psychiatric hospitalization among a Veterans Administration database of patients with dementia and comorbid bipolar disorder (D+BD). Patients with D+BD had a greater prevalence of psychiatric hospitalization (28% vs 4%). The strongest predictor of psychiatric hospitalization was the presence of an alcohol use disorder (51% risk); patients without alcohol use disorders but under the age of 70 had the next highest risk (33% risk). However, patients with an alcohol use disorder had shorter psychiatric hospitalizations than those without. Compared with patients without BD, D+BD patients were more likely to have alcohol use disorders (15% vs 3%) and any other substance use problem (10% vs 1%). In patients diagnosed with dementia and bipolar disorder, the strongest risk factor for psychiatric hospitalization was an alcohol abuse disorder. These findings suggest that disorders with increased frequency in BD affect the course of dementia.

    View details for DOI 10.1177/0891988706286215

    View details for Web of Science ID 000237778800003

    View details for PubMedID 16690991

  • Caution regarding the use of pilot studies to guide power calculations for study proposals ARCHIVES OF GENERAL PSYCHIATRY Kraemer, H. C., Mintz, J., Noda, A., Tinklenberg, J., Yesavage, J. A. 2006; 63 (5): 484-489

    Abstract

    Clinical researchers often propose (or review committees demand) pilot studies to determine whether a study is worth performing and to guide power calculations. The most likely outcomes are that (1) studies worth performing are aborted and (2) studies that are not aborted are underpowered. There are many excellent reasons for performing pilot studies. The argument herein is not meant to discourage clinical researchers from performing pilot studies (or review committees from requiring them) but simply to caution against their use for the objective of guiding power calculations.

    View details for Web of Science ID 000237215800002

    View details for PubMedID 16651505

  • The brain-derived neurotrophic factor Val66Met polymorphism and rate of decline in Alzheimer's disease JOURNAL OF ALZHEIMERS DISEASE Chuu, J. Y., Taylor, J. L., Tinklenberg, J., Noda, A., Yesavage, J., Murphy, G. M. 2006; 9 (1): 43-49

    Abstract

    It is largely unknown why some patients with Alzheimer's disease (AD) decline cognitively more rapidly than others. Genetic differences among patients could influence rate of decline. Brain-derived neurotrophic factor (BDNF) is a neurotrophin important in the survival neurons and in memory function. BDNF levels are reduced in the brain in AD. The Val66Met polymorphism in the BDNF gene modifies neuronal BDNF secretion, and affects hippocampal function and memory performance. We tested the hypothesis that the BDNF Val66Met polymorphism influences rate of cognitive decline in AD. In a sample of 149 AD patients followed for an average of 3.9 years, we found no effect of BDNF Val66Met genotype on rate of change in the Mini Mental State Examination. Results were similar when we excluded patients taking an acetylcholinesterase inhibitor, those placed in a nursing home during the study, or those with a neuropathological diagnosis that included AD plus an entity other than AD. We also found no evidence that the effects of the BDNF Val66Met genotype depend on APOE genotype, which itself had no effect on rate of cognitive change. These findings suggest that the functional BDNF Val66Met variant is not a major determinant of rate of cognitive decline in AD.

    View details for Web of Science ID 000237795900004

    View details for PubMedID 16627933

  • Factors in choosing atypical antipsychotics: Toward understanding the bases of physicians' prescribing decisions JOURNAL OF PSYCHIATRIC RESEARCH Hoblyn, J., Noda, A., Yesavage, J. A., Brooks, J. O., Sheikh, J., Lee, T., Tinklenberg, J. R., Schneider, B., O'Hara, R., Leslie, D. L., Rosenheck, R. A., Kraemer, H. C. 2006; 40 (2): 160-166

    Abstract

    Off-label prescribing of medications, polypharmacy, and other questionable prescribing practices have led investigators to examine a large VA pharmacy database to determine if physician prescribing decisions appear reasonable.The current study addresses the question of physician prescribing of atypical antipsychotics in 34,925 veterans with schizophrenia, using a series of signal detection analyses.These results suggest that only three factors (hospital size, age, and secondary diagnosis) allow classification of patients prescribed atypicals into three groups with frequencies of use of atypicals ranging from 43% to 79%, and that these results are consistent with reasonable clinical practice.Results of two-stage signal detection analyses are readily interpretable by clinicians and administrators who are faced with the task of evaluating how physicians prescribe medications in clinical practice. Physicians' decisions to prescribe atypical antipsychotics are based on both patient and fiscal considerations. This likely reflects a combination of clinical judgment and institutional guidelines.

    View details for DOI 10.1016/j.jpsychires.2005.06.004

    View details for Web of Science ID 000235641200009

    View details for PubMedID 16150458

  • Hormone replacement therapy and longitudinal cognitive performance in postmenopausal women AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY O'Hara, R., Schroder, C. M., Bloss, C., Bailey, A. M., Alyeshmerni, A. M., Mumenthaler, M. S., Friedman, L. F., Yesavage, J. A. 2005; 13 (12): 1107-1110

    Abstract

    The authors examined the impact of hormone replacement therapy (HRT) on longitudinal cognitive performance (controlling for mood state) in 69 community-dwelling, postmenopausal women.The authors conducted a 5-year follow-up of cognitive performance in 37 postmenopausal HRT users and 32 non-users. The groups did not differ with respect to age, years of education, or inter-test interval.No main effect of HRT was observed on any of the cognitive measures, and depressive symptomatology did not affect the relationship between HRT and cognition.Overall, our findings do not suggest that HRT affects longitudinal cognitive performance in postmenopausal, community-dwelling older women.

    View details for Web of Science ID 000233614500011

    View details for PubMedID 16319304

  • Nocturnal sleep apnea/hypopnea is associated with lower memory performance in APOE epsilon 4 carriers NEUROLOGY O'Hara, R., Schroder, C. M., Kraemer, H. C., Kryla, N., Cao, C., Miller, E., Schatzberg, A. F., Yesavage, J. A., Murphy, G. M. 2005; 65 (4): 642-644

    Abstract

    The authors investigated the relationship between obstructive sleep apnea/hypopnea (OSAH) and cognition in 36 older adults, 18 APOE epsilon4 carriers, and 18 non-carriers. Greater numbers of respiratory events negatively impacted memory function in epsilon4 carriers only. This is the first study to provide preliminary evidence for a negative interaction of APOE epsilon4 and OSAH on memory in older adults, which may have important implications for treating cognitive decline and delaying dementia onset.

    View details for Web of Science ID 000231371600035

    View details for PubMedID 16116137

  • Relating medial temporal lobe volume to frontal fMRI activation for memory encoding in older adults CORTEX Rosen, A. C., Gabrieli, J. D., Stoub, T., Prull, M. W., O'Hara, R., Yesavage, J., DeToledo-Morrell, L. 2005; 41 (4): 595-602

    Abstract

    Neuroimaging research on the brain basis of memory decline in older adults typically has examined age-related changes either in structure or in function. Structural imaging studies have found that smaller medial temporal lobe (MTL) volumes are associated with lower memory performance. Functional imaging studies have found that older adults often exhibit bilateral frontal-lobe activation under conditions where young adults exhibit unilateral frontal activation. As yet, no one has examined whether these MTL structural and frontal-lobe functional findings are associated. In this study, we tested whether these findings were correlated in a population of healthy older adults in whom we previously demonstrated verbal memory performance was positively associated with left entorhinal cortex volume in the MTL (Rosen et al., 2003) and right frontal lobe activation during memory encoding (Rosen et al., 2002). Thirteen, non-demented, community-dwelling older adults participated both in a functional MRI (fMRI) study of verbal memory encoding and structural imaging. MRI-derived left entorhinal volume was measured on structural images and entered as a regressor against fMRI activation during verbal memory encoding. Right frontal activation (Brodmann's Area 47/insula) was positively correlated with left entorhinal cortex volume. These findings indicate a positive association between MTL volume and right frontal-lobe function that may underlie variability in memory performance among the elderly, and also suggest a two-stage model of memory decline in aging.

    View details for Web of Science ID 000230574200015

    View details for PubMedID 16042035

  • Tolerability and effectiveness of lamotrigine in complex elderly patients JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Aulakh, J. S., Hawkins, J. W., Athwal, H. S., Sheikh, J. I., Yesavage, J., Tinklenberg, J. R. 2005; 18 (1): 8-11

    Abstract

    There is paucity of medical literature on the use of lamotrigine in elderly patients who have behavior problems and diverse psychiatric syndromes. This article is a retrospective case series summarizing the authors' experience with this medication. In a 20-patient case series from an institutional review board-approved retrospective chart review, the tolerability and efficacy of lamotrigine was evaluated for the management of agitated and aggressive behaviors in nursing home patients with a range of psychiatric and medical diagnoses. Nineteen of the elderly nursing home patients tolerated lamotrigine treatment, and 18 showed modest clinical improvement. These results support the authors' belief that controlled clinical investigations of this medication should be performed.

    View details for DOI 10.1177/0891988704271762

    View details for Web of Science ID 000226923100002

    View details for PubMedID 15681622

  • Cognitive ability, expertise, and age differences in following air-traffic control instructions PSYCHOLOGY AND AGING Taylor, J. L., O'Hara, R., Mumenthaler, M. S., Rosen, A. C., Yesavage, J. A. 2005; 20 (1): 117-133

    Abstract

    Differences in cognitive ability and domain-specific expertise may help explain age differences in pilot performance. Pilots heard air-traffic controller messages and then executed them while "flying" in a simulator. Messages varied in length and speech rate. Age was associated with lower accuracy, but the expected Age x Message Difficulty interactions were not obtained. Expertise, as indexed by pilot ratings, was associated with higher accuracy; yet expertise did not reduce age differences in accuracy. The effect of age on communication task accuracy was largely explainable as an age-associated decrease in working memory span, which in turn was explainable as decreases in both speed and interference control. Results are discussed within frameworks of deliberate practice and cognitive mediation of age differences.

    View details for DOI 10.1037/0882-7974.20.1.117

    View details for Web of Science ID 000227731300009

    View details for PubMedID 15769218

  • The development and initial validation of the Terminally Ill Grief or Depression Scale (TIGDS) INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH Periyakoil, V. S., Kraemer, H. C., Noda, A., Moos, R., Hallenbeck, J., Webster, M., Yesavage, J. A. 2005; 14 (4): 202-212

    Abstract

    Patients often experience 'preparatory-grief' as they cope with the dying process. Some may be depressed. The Terminally Ill Grief or Depression Scale (TIGDS), comprising grief and depression sub-scales, is a new self-report measure designed to differentiate between preparatory-grief and depression in adult inpatients. The initial 100-item inventory was assembled based on literature review, interviews with clinicians and dying patients and then shortened to 42 items based on consensus expert opinion. Validity and reliability were tested in a sample of 55 terminally ill adults. The consensus clinical opinion was used as the gold standard to differentiate between preparatory grief and depression. The intra-class correlation coefficient was high (it was calculated to estimate the test-retest reliability for the 47 patients who had completed the TIGDS twice--retest was administered 2 to 7 days after the initial test), ranging from 0.86 (grief) to 0.97 (depression). The validity of TIGDS was assessed using a receiver operating characteristic curve analysis, comparing the first test with the clinical criterion. The first and only variable and cut-point was the depression score (chi-square = 18.4, p < 0.001, cut point = 3). The sensitivity of the TIGDS was 0.727 and specificity was 0.886 for the depression = 3 cutoff score. The construct validity of the TIGDS was tested by comparing with the Hospital Anxiety and Depression Scale (HADS). The TIGDS depression subscale showed strong convergent validity and the TIGDS grief subscale showed strong discriminant validity with the HADS total score.

    View details for DOI 10.1002/mpr.8

    View details for Web of Science ID 000234094000003

    View details for PubMedID 16395873

  • Sleep and circadian abnormalities in a transgenic mouse model of Alzheimer's disease: A role for cholinergic transmission NEUROSCIENCE Wisor, J. P., Edgar, D. M., Yesavage, J., Ryan, H. S., McCormick, C. M., Lapustea, N., Murphy, G. M. 2005; 131 (2): 375-385

    Abstract

    The Tg2576 mouse model of Alzheimer's disease (AD) exhibits age-dependent amyloid beta (Abeta) deposition in the brain. We studied electroencephalographically defined sleep and the circadian regulation of waking activities in Tg2576 mice to determine whether these animals exhibit sleep abnormalities akin to those in AD. In Tg2576 mice at all ages studied, the circadian period of wheel running rhythms in constant darkness was significantly longer than that of wild type mice. In addition, the increase in electroencephalographic delta (1-4 Hz) power that occurs during non-rapid eye movement sleep after sleep deprivation was blunted in Tg2576 mice relative to controls at all ages studied. Electroencephalographic power during non-rapid eye movement sleep was shifted to higher frequencies in plaque-bearing mice relative to controls. The wake-promoting efficacy of the acetylcholinesterase inhibitor donepezil was lower in plaque-bearing Tg2576 mice than in controls. Sleep abnormalities in Tg2576 mice may be due in part to a cholinergic deficit in these mice. At 22 months of age, two additional deficits emerged in female Tg2576 mice: time of day-dependent modulation of sleep was blunted relative to controls and rapid eye movement sleep as a percentage of time was lower in Tg2576 than in wild type controls. The rapid eye movement sleep deficit in 22 month-old female Tg2576 mice was abolished by brief passive immunization with an N-terminal antibody to Abeta. The Tg2576 model provides a uniquely powerful tool for studies on the pathophysiology of and treatments for sleep deficits and associated cholinergic abnormalities in AD.

    View details for DOI 10.1016/j.neuroscience.2004.11.018

    View details for Web of Science ID 000227258400011

    View details for PubMedID 15708480

  • The measurement of sleep by actigraphy: Direct comparison of 2 commercially available actigraphs in a nonclinical population SLEEP Benson, K., Friedman, L., Noda, A., Wicks, D., Wakabayashi, E., Yesavage, J. 2004; 27 (5): 986-989

    Abstract

    To compare 2 commercially available actigraphs.Subjects wore the Actiwatch L and the Basic Mini-Motionlogger for 2 nights.Naturalistic.20 healthcare workers aged 24 to 64 years.Measures included sleep latency, total sleep time, wake after sleep onset, and sleep efficiency. Actiwatch L data were analyzed at 3 sensitivity settings.The Mini-Motionlogger reported more total sleep time, less wake after sleep onset, and greater sleep efficiency than the Actiwatch L set at high sensitivity. It also reported more wake after sleep onset than the Actiwatch L set at low sensitivity.Both devices achieved similar overall performance when the Actiwatch L was set at medium sensitivity.

    View details for Web of Science ID 000223451400023

    View details for PubMedID 15453559

  • Validation of a 26-point telephone version of the mini-mental state examination JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Newkirk, L. A., Kim, J. A., Thompson, J. M., Tinklenberg, J. R., Yesavage, J. A., Taylor, J. L. 2004; 17 (2): 81-87

    Abstract

    The objective of this study was to assess the convergent validity of a 26-point Telephone Mini-Mental State Examination (MMSE) in a longitudinal cohort of 46 Alzheimer's disease (AD) patients. Paired in-person and telephone MMSE observations were collected within 35 days of each other. The setting was the Stanford/VA Alzheimer's Center in Palo Alto, California, and patients' residences. The 30-point Folstein MMSE was administered in-person, and a 26-point telephone version of the MMSE, adapted from the Adult Lifestyles and Function Interview (ALFI)-MMSE. Total scores for the in-person and telephone MMSE versions correlated strongly (Pearson's r =.88, P <.001). Hearing impairment and education level did not significantly affect telephone-based performance. The Telephone MMSE can be used to validly estimate in-person MMSE scores of patients with AD. Use of this practical measure can enhance reassessment if returning to the clinic is difficult or if a change in the patient's medical condition merits a check of mental status by telephone.

    View details for DOI 10.1177/0891988704264534

    View details for Web of Science ID 000223475100005

    View details for PubMedID 15157348

  • VA practice patterns and practice guidelines for treating posttraumatic stress disorder JOURNAL OF TRAUMATIC STRESS Rosen, C. S., Chow, H. C., Finney, J. F., Greenbaum, M. A., Moos, R. H., Sheikh, J. I., Yesavage, J. A. 2004; 17 (3): 213-222

    Abstract

    Little is known about how recent ISTSS practice guidelines (E. B. Foa, T. M. Keane, & M. J. Friedman, 2000) compare with prevailing PTSD treatment practices for veterans. Prior to guideline dissemination, clinicians in 6 VA medical centers were surveyed in 1999 (n = 321) and in 2001 (n = 271) regarding their use of various assessment and treatment procedures. Practices most consistent with guideline recommendations included psychoeducation, coping skills training, attention to trust issues, depression and substance use screening, and prescribing of SSRIs, anticonvulsants, and trazodone. PTSD and trauma assessment, anger management, and sleep hygiene practices were provided less consistently. Exposure therapy was rarely used. Additional research is needed on training, clinical resources, and organizational factors that may influence VA implementation of guideline recommendations.

    View details for Web of Science ID 000221686900004

    View details for PubMedID 15253093

  • Sleep/wake disruption in Alzheimer's disease: APOE status and longitudinal course JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Yesavage, J. A., Friedman, L., Kraemer, H., Tinklenberg, J. R., Salehi, A., Noda, A., Taylor, J. L., O'Hara, R., Murphy, G. 2004; 17 (1): 20-24

    Abstract

    Disturbed sleep is a major clinical problem in Alzheimer's disease (AD). Apolipoprotein epsilon4 (APOE epsilon4) carrier status may increase risk of AD, yet there are no data on relations between APOE status and progression of sleep disturbance in AD. The objective of this study was to determine if sleep parameters in AD patients change over time as a function of APOE carrier status. Forty-four community-dwelling AD patients with diagnosis of probable AD were followed from early stages of disease. Their sleep/wake parameters were compared according to APOE status. For APOE epsilon4 carriers, only wake after sleep onset (WASO) increased in association with lower cognitive function as indicated by the Mini-Mental State Examination (MMSE); for non-epsilon4 subjects, increases in WASO and declines in total sleep time, sleep efficiency, and the amplitude of the rest/activity circadian rhythm over time were associated with lower performance on the MMSE. In these data, APOE status was associated with the progression of sleep/wake disturbances in AD. Overall, there was greater deterioration on sleep parameters in patients negative for the epsilon4 allele.

    View details for DOI 10.1117/0891988703261994

    View details for Web of Science ID 000223474900004

    View details for PubMedID 15018693

  • Use of a VA pharmacy database to screen for areas at high risk for disease: Parkinson's disease and exposure to pesticides JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Yesavage, J. A., Sheikh, J., Noda, A., Murphy, G., O'Hara, R., Hierholzer, R., Battista, M., Ashford, J. W., Kraemer, H. C., Tinklenberg, J. 2004; 17 (1): 36-38

    Abstract

    The purpose of this study was to assess whether pharmacy database information from US Department of Veterans Affairs (VA) medical centers could be used to screen for areas of higher Parkinson's disease prevalence in patients exposed to pesticides. The authors used pharmacy data sets and compared the use of antiparkinsonian medications at 2 VA medical centers in California: one in Palo Alto, near the ocean, and one in Fresno, downwind from extensively farmed parts of the Central Valley. They found that patients at Fresno had higher odds ratios (1.5-1.8) for the use of Parkinson's disease medications than patients at Palo Alto. These data are consistent with the observations of prior epidemiologic studies and suggest that VA pharmacy databases can prioritize locations for further epidemiologic research. However, a thorough exploration of alternative explanations is needed to reach definitive conclusions regarding the findings suggested by this method.

    View details for DOI 10.1117/0891988703258672

    View details for Web of Science ID 000223474900007

    View details for PubMedID 15018696

  • Differential associations between entorhinal and hippocampal volumes and memory performance in older adults BEHAVIORAL NEUROSCIENCE Rosen, A. C., Prull, M. W., Gabrieli, J. D., Stoub, T., O'Hara, R., Friedman, L., Yesavage, J. A., DeToledo-Morrell, L. 2003; 117 (6): 1150-1160

    Abstract

    Magnetic resonance imaging-derived entorhinal and hippocampal volumes were measured in 14 nondemented, community-dwelling older adults. Participants were selected so that memory scores from 2 years prior to scanning varied widely but were not deficient relative to age-appropriate norms. A median split of these memory scores defined high-memory and low-memory groups. Verbal memory scores at the time of imaging were lower, and entorhinal and hippocampal volumes were smaller, in the low-memory group than in the high-memory group. Left entorhinal cortex volume showed the strongest correlation (r= .79) with immediate recall of word lists. Left hippocampal volume showed the strongest correlation (r= .57) with delayed paragraph recall. These results suggest that entorhinal and hippocampal volumes are related to individual differences in dissociable kinds of memory performance among healthy older adults.

    View details for DOI 10.1037/0735-7044.117.6.1150

    View details for Web of Science ID 000187402300004

    View details for PubMedID 14674836

  • Age and disease severity predict choice of atypical neuroleptic: a signal detection approach to physicians' prescribing decisions JOURNAL OF PSYCHIATRIC RESEARCH Yesavage, J. A., Hoblyn, J., Sheikh, J., Tinklenberg, J. R., Noda, A., O'Hara, R., Fenn, C., Mumenthaler, M. S., Friedman, L., Kraemer, H. C. 2003; 37 (6): 535-538

    Abstract

    We used a novel application of a signal detection technique, receiver operator characteristics (ROC), to describe factors entering a physician's decision to switch a patient from a typical high potency neuroleptic to a particular atypical, olanzapine (OLA) or risperidone (RIS).ROC analyses were performed on pharmacy records of 476 VA patients who had been treated on a high potency neuroleptic then changed to either OLA or RIS.Overall 68% patients switched to OLA and 32% to RIS. The best predictor of neuroleptic choice was age at switch, with 78% of patients aged less than 55 years receiving OLA and 51% of those aged greater than or equal to 55 years receiving OLA (chi(2)=38.2, P<0.001). Further analysis of the former group indicated that adding the predictor of one or more inpatient days to age increased the likelihood of an OLA switch from 78% to 85% (chi(2)=7.3, P<0.01) while further analysis of the latter group indicated that adding the predictor of less than 10 inpatients days to age decreased the likelihood of an OLA switch from 51% to 45% (chi(2)=7.0, P<0.01).ROC analyses have the advantage over other analyses, such as regression techniques, insofar as their "cut-points" are readily interpretable, their sequential use forms an intuitive "decision tree" and allows the potential identification of clinically relevant "subgroups". The software used in this analysis is in the public domain (http://mirecc.stanford.edu).

    View details for DOI 10.1016/S0022-3956(03)00053-0

    View details for Web of Science ID 000186239700010

    View details for PubMedID 14563385

  • Development of diagnostic criteria for defining sleep disturbance in Alzheimer's disease JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Yesavage, J. A., Friedman, L., Ancoli-Israel, S., Bliwise, D., Singer, C., Vitiello, M. V., Monjan, A. A., Lebowitz, B. 2003; 16 (3): 131-139

    Abstract

    This article proposes new standards for identifying, defining, and naming sleep/wake cycle disturbances associated with Alzheimer's disease (AD) to aid in more effective research, including the development and testing of potential treatments. Many AD patients develop sleep/wake cycle disturbances associated with distress, depression, and sleep disturbances in the caregiver, as well as early nursing home placement for the patient. The Food and Drug Administration Psychopharmacological Drugs Advisory Committee has emphasized the need for a comprehensive diagnostic system. A key point made by the committee was that behavioral problems associated with dementia (including sleep and chronobiological disturbances) are scientifically and clinically valid targets of pharmacologic treatment. However, current diagnostic criteria preclude development of FDA-acceptable studies of pharmacological interventions because they do not include the required specific indications for treatment. This article attempts to develop better-defined provisional criteria with the goal of promoting epidemiological, physiological, and, especially, pharmacological research on sleep/wake disturbances.

    View details for DOI 10.1177/0891988703255684

    View details for Web of Science ID 000223380400001

    View details for PubMedID 12967054

  • Psychoactive drugs and pilot performance: A comparison of nicotine, donepezil, and alcohol effects NEUROPSYCHOPHARMACOLOGY Mumenthaler, M. S., Yesavage, J. A., Taylor, J. L., O'Hara, R., Friedman, L., LEE, H., Kraemer, H. C. 2003; 28 (7): 1366-1373

    Abstract

    The cholinergic system plays a major role in cognitive abilities that are essential to piloting an aircraft: attention, learning, and memory. In previous studies, drugs that enhance the cholinergic system through different pharmacologic mechanisms have shown beneficial effects on cognition; but dissimilar cognitive measures were used and samples were not comparable. A comparison within the same cognitive tasks, within comparable samples appears desirable. Toward this aim, we compared effect sizes (ES) of performance-enhancing doses of nicotine (a nicotinic receptor agonist) and donepezil (an acetylcholinesterase inhibitor) as found in our prior work on pilot performance. We also compared cholinergic ES to those of performance-impairing doses of alcohol. In three randomized, placebo-controlled trials, we assessed the flight performance of aircraft pilots in a Frasca 141 simulator, testing I: the acute effects of nicotine gum 2 mg; II: the effects of administration of 5 mg donepezil/day for 30 days; and III: the acute and 8 h-carryover effects of alcohol after a target peak BAC of 0.10%. We calculated the ES of nicotine, donepezil, and alcohol on a flight summary score and on four flight component scores. Compared to placebo, nicotine and donepezil significantly improved, while alcohol significantly impaired overall flight performance: ES (nicotine)=0.80; ES (donepezil)=1.02; ES (alcohol acute)=-3.66; ES (alcohol 8 h)=-0.82. Both cholinergic drugs showed the largest effects on flight tasks requiring sustained visual attention. Although the two tested cholinergic drugs have different pharmacologic mechanisms, their effects on flight performance were similar in kind and size. The beneficial effects of the cholinergic drugs on overall flight performance were large and the absolute (ie nondirectional) sizes were about one-fourth of the absolute ES of acute alcohol intoxication and roughly the same as the absolute 8 h-carryover ES of alcohol.

    View details for DOI 10.1038/sj.npp.1300202

    View details for Web of Science ID 000183773000018

    View details for PubMedID 12784106

  • Use of an external mnemonic to augment the efficacy of an internal mnemonic in older adults INTERNATIONAL PSYCHOGERIATRICS Brooks, J. O., Friedman, L., Yesavage, J. A. 2003; 15 (1): 59-67

    Abstract

    To evaluate the impact of external memory devices on the efficacy of a package of internal mnemonic techniques. Participants wrote two types of lists during the study phase: (a) a list of study words and/or (b) a loci list. At recall, participants were not allowed to refer to either of the lists they had written during the study.2 x 2 factorial with writing study words ("write" or "not write") and writing down a previously established loci list ("write" or "not write") manipulated as between-participants variables.68 community-dwelling adults 55 years of age and older who wished to improve their memory.Free word recall.There were statistically significant effects of writing the loci list, but not of writing the list of study words. Scores were higher when participants wrote the loci lists compared to when they did not.Use of external mnemonics may enhance the efficacy of internal mnemonics, even when the external mnemonic is not used at the time of recall.

    View details for Web of Science ID 000183289600007

    View details for PubMedID 12834200

  • Variable effects of aging on frontal lobe contributions to memory NEUROREPORT Rosen, A. C., Prull, M. W., O'Hara, R., Race, E. A., Desmond, J. E., Glover, G. H., Yesavage, J. A., Gabrieli, J. D. 2002; 13 (18): 2425-2428

    Abstract

    Declarative memory declines with age, but there is profound variation in the severity of this decline. Healthy elderly adults with high or low memory scores and young adults viewed words under semantic or non-semantic encoding conditions while undergoing fMRI. Young adults had superior memory for the words, and elderly adults with high memory scores had better memory for the words than those with low memory scores. The elderly with high scores had left lateral and medial prefrontal activations for semantic encoding equal to the young, and greater right prefrontal activation than the young. The elderly with low scores had reduced activations in all three regions relative to the elderly with high memory scores. Thus, successful aging was characterized by preserved left prefrontal and enhanced right prefrontal activation that may have provided compensatory encoding resources.

    View details for DOI 10.1097/01.wnr.0000048001.96487.05

    View details for Web of Science ID 000180673200010

    View details for PubMedID 12499842

  • Ethical, and practical issues in applying functional imaging to the clinical management of Alzheimer's disease BRAIN AND COGNITION Rosen, A. C., Bokde, A. L., Pearl, A., Yesavage, J. A. 2002; 50 (3): 498-519

    Abstract

    This review outlines ethical, legal, and practical issues related to conducting functional imaging research with Alzheimer's disease (AD) patients. Imaging techniques, with an emphasis on functional MRI and positron emission tomography, are compared and contrasted with respect to the manner in which they can be applied to issues of clinical relevance to AD. Methodological difficulties are raised to assist with critical evaluation of current imaging results. Various potential clinical applications of functional imaging are briefly reviewed and discussed with respect to associated ethical conflicts.

    View details for Web of Science ID 000180058100013

    View details for PubMedID 12480493

  • Modeling the prevalence and incidence of Alzheimer's disease and mild cognitive impairment JOURNAL OF PSYCHIATRIC RESEARCH Yesavage, J. A., O'Hara, R., Kraemer, H., Noda, A., Taylor, J. L., Ferris, S., Gely-Nargeot, M. C., Rosen, A., Friedman, L., Sheikh, J., Derouesne, C. 2002; 36 (5): 281-286

    Abstract

    A number of systems have been proposed for classifying older adults who suffer from cognitive impairment or decline but do not yet meet criteria for Alzheimer's disease (AD). The classification, Mild Cognitive Impairment (MCI), has attracted much attention. It uses relatively specific diagnostic criteria and individuals who meet these criteria appear to be at substantial risk for the development of AD. However, little data is available to define the prevalence of MCI in any age group. We propose a simple mathematical model for the progression of patients from Non-Affected (NA) to MCI to AD. This first-order Markov model defines the likely prevalence of MCI at specific ages. Primary assumptions of the model include an AD prevalence of 1% at age 60 increasing to 25% at age 85 and a conversion rate from MCI to AD of 10% constant across all ages considered. We used the best available information for our model and found (1) that the MCI prevalence increased from 1% at age 60 to 42% at age 85 and (2) that the conversion rate from NA to MCI increased from 1% per year at age 60 to 11% at age 85. In conclusion, this model allows estimation of prevalence of MCI and conversion from NA to MCI based upon known prevalences of AD, conversion rates of MCI to AD, and death rates. Due to its substantial prevalence, MCI may be an important target for screening and possible intervention.

    View details for Web of Science ID 000178254700002

    View details for PubMedID 12127595

  • Interactive influences on BVRT performance level: geriatric considerations ARCHIVES OF CLINICAL NEUROPSYCHOLOGY Coman, E., Moses, J. A., Kraemer, H. C., Friedman, L., Benton, A. L., Yesavage, J. 2002; 17 (6): 595-610

    Abstract

    We examined the interactive influence of specific demographic and diagnostic variables on Benton Visual Retention Test (BVRT) performance in three commonly presenting groups of older adults. Cross-sectional data from three archival samples were utilized: "normals" (n=156), "normals with memory concerns" (n=435), and a "mixed neurologic" group (n=196). In both normal groups, as well as in a "no/low deficit" neurologic subgroup, we confirmed that the higher one's age, the lower their BVRT accuracy, while the higher one's level of education, the greater their BVRT accuracy (at least through age 84). For normal subjects, gender had no impact on BVRT performance. Variability in BVRT performance increased consistently, but not significantly, through age 85.

    View details for Web of Science ID 000178747900006

    View details for PubMedID 14591858

  • Donepezil and flight simulator performance: Effects on retention of complex skills NEUROLOGY Yesavage, J. A., Mumenthaler, M. S., Taylor, J. L., Friedman, L., O'Hara, R., Sheikh, J., Tinklenberg, J., Whitehouse, P. J. 2002; 59 (1): 123-125

    Abstract

    We report a randomized, double-blind, parallel group, placebo-controlled study to test the effects of the acetylcholinesterase inhibitor, donepezil (5 mg/d for 30 days), on aircraft pilot performance in 18 licensed pilots with mean age of 52 years. After 30 days of treatment, the donepezil group showed greater ability to retain the capacity to perform a set of complex simulator tasks than the placebo group, p < 0.05. Donepezil appears to have beneficial effects on retention of training on complex aviation tasks in nondemented older adults.

    View details for Web of Science ID 000176622600025

    View details for PubMedID 12105320

  • Sleep/wake cycle disturbance in Alzheimer's disease: How much is due to an inherent trait? INTERNATIONAL PSYCHOGERIATRICS Yesavage, J. A., Taylor, J. L., Kraemer, H., Noda, A., Friedman, L., Tinklenberg, J. R. 2002; 14 (1): 73-81

    Abstract

    Major advances in understanding the physiology and genetics of circadian rhythm in the past decade challenge the researcher of sleep/wake disorders in Alzheimer's disease (AD) to distinguish patient characteristics stable across the course of illness ("traits") from characteristics that vary with stage of illness ("states"). A components-of-variance approach with a repeated measures model was used to examine the between-subjects variance over time ("trait") vs. within-subjects ("state") variance in 42 patients with probable AD followed, on average, over 2 years on actigraphic sleep/wake measures. Mental status scores indexed stage of illness. Actigraphic measures of sleep efficiency and circadian rhythmicity appeared predominantly "trait," with between-individual differences accounting for over 55% of variance compared to the less than 5% of variance related to stage of cognitive impairment. We discuss how "state-trait" analyses can be helpful in identifying areas of assessment most likely to be fruitful objectives of physiologic and genetic research on sleep/wake disturbance in AD.

    View details for Web of Science ID 000176217400008

    View details for PubMedID 12094910

  • How well are clinicians following dementia practice guidelines? ALZHEIMER DISEASE & ASSOCIATED DISORDERS Rosen, C. S., Chow, H. C., Greenbaum, M. A., Finney, J. F., Moos, R. H., Sheikh, J. I., Yesavage, J. A. 2002; 16 (1): 15-23

    Abstract

    Although there are numerous clinical guidelines regarding the management of dementia, there have been few studies on their implementation in practice. Clinicians in six United States Department of Veterans Affairs medical centers (n = 200, 85% response rate) were surveyed regarding their use of practices recommended in the California Workgroup Guidelines for Alzheimer's Disease Management. The majority of providers (89% to 73%) reported that they routinely conducted neurological examinations, obtained histories from caregivers, discussed the diagnosis with the patient's family, discussed durable power of attorney, and made legally-required reports of drivers with dementia. Roughly two-thirds of providers said they routinely conducted cognitive screening examinations, screened for depression, reported elder abuse, and discussed care needs and decision-making issues with patients' families. Only half of all outpatient providers implemented caregiver support practices for at least half of their patients. Clinicians' choices of medications for cognition, mood, and behavior problems were broadly consistent with current practice guidelines. These results suggest possible priorities for quality improvement efforts. Further research is needed to clarify reasons for particular gaps between guidelines and practice and to identify specific targets for intervention.

    View details for Web of Science ID 000174273000003

    View details for PubMedID 11882745

  • Which Alzheimer patients are at risk for rapid cognitive decline? JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY O'Hara, R., Thompson, J. M., Kraemer, H. C., Fenn, C., Taylor, J. L., Ross, L., Yesavage, J. A., Bailey, A. M., Tinklenberg, J. R. 2002; 15 (4): 233-238

    Abstract

    In the current study of 1062 Alzheimer's disease (AD) patients, we employed receiver operating characteristic curve analysis to identify characteristics of patients at increased risk for rapid cognitive decline. The patients are participants at one of the nine Alzheimer's Disease Research Centers of California. Rapid decline was defined as a 3-point or greater loss on the Mini-Mental State Examination (MMSE) per year, post visit. The independent variables were age at clinic visit, age at symptom onset of AD, MMSE at patient visit, years of education, gender, ethnicity, living arrangement, presence of aphasia, delusions, hallucinations, and extrapyramidal signs. Receiver operating characteristic curve analysis indicated that AD patients presenting with moderate to severe aphasia, age at clinic visit of 75 years or less, and an MMSE greater than 7 were at increased risk for rapid cognitive decline. This information could help clinicians target these patients for pharmacologic interventions, facilitate long-term care planning, and potentially create savings by delaying or stabilizing the course of the disease.

    View details for Web of Science ID 000179584400009

    View details for PubMedID 12489920

  • CSF hypocretin/orexin levels in narcolepsy and other neurological conditions NEUROLOGY Ripley, B., Overeem, S., Fujiki, N., Nevsimalova, S., Uchino, M., Yesavage, J., Di Monte, D., DOHI, K., Melberg, A., Lammers, G. J., Nishida, Y., Roelandse, F. W., Hungs, M., Mignot, E., Nishino, S. 2001; 57 (12): 2253-2258

    Abstract

    To examine the specificity of low CSF hypocretin-1 levels in narcolepsy and explore the potential role of hypocretins in other neurologic disorders.A method to measure hypocretin-1 in 100 microL of crude CSF sample was established and validated. CSF hypocretin-1 was measured in 42 narcolepsy patients (ages 16-70 years), 48 healthy controls (ages 22-77 years,) and 235 patients with various other neurologic conditions (ages 0-85 years).As previously reported, CSF hypocretin-1 levels were undetectably low (<100 pg/mL) in 37 of 42 narcolepsy subjects. Hypocretin-1 levels were detectable in all controls (224-653 pg/mL) and all neurologic patients (117-720 pg/mL), with the exception of three patients with Guillain-Barré syndrome (GBS). Hypocretin-1 was within the control range in most neurologic patients tested, including patients with AD, PD, and MS. Low but detectable levels (100-194 pg/mL) were found in a subset of patients with acute lymphocytic leukemia, intracranial tumors, craniocerebral trauma, CNS infections, and GBS.Undetectable CSF hypocretin-1 levels are highly specific to narcolepsy and rare cases of GBS. Measuring hypocretin-1 levels in the CSF of patients suspected of narcolepsy is a useful diagnostic procedure. Low hypocretin levels are also observed in a large range of neurologic conditions, most strikingly in subjects with head trauma. These alterations may reflect focal lesions in the hypothalamus, destruction of the blood brain barrier, or transient or chronic hypofunction of the hypothalamus. Future research in this area is needed to establish functional significance.

    View details for Web of Science ID 000172891500018

    View details for PubMedID 11756606

  • Influence of the menstrual cycle on flight simulator performance after alcohol ingestion JOURNAL OF STUDIES ON ALCOHOL Mumenthaler, M. S., O'Hara, R., Taylor, J. L., Friedman, L., Yesavage, J. A. 2001; 62 (4): 422-433

    Abstract

    Previous studies investigating the influence of the menstrual cycle on cognitive functioning of women after alcohol ingestion have obtained inconsistent results. The present study tested the hypothesis that flight simulator performance during acute alcohol intoxication and 8 hours after drinking differs between the menstrual and the luteal phase of the menstrual cycle.White female pilots (N = 24) were tested during the menstrual and the luteal phases of their menstrual cycles. On each test day they performed a baseline simulator flight, consumed 0.67 g/kg ethanol, and performed an acute-intoxication and an 8-hour-carryover simulator flight.Subjects reached highly significant increases in estradiol (E2) as well as progesterone (P) levels during the luteal test day. Yet, there were no significant differences in overall flight performance after alcohol ingestion between the menstrual and luteal phases during acute intoxication or at 8-hour carryover. We found no correlations between E, or P levels and overall flight performance. However, there was a statistically significant Phase x Order interaction: Pilots who started the experiment with their menstrual day were less susceptible to the effects of alcohol during the second test day than were pilots who started with their luteal day.The tested menstrual cycle phases and varying E2 and P levels did not significantly influence postdrink flight performance. Because the present study included a comparatively large sample size and because it involved complex "real world" tasks (piloting an aircraft), we believe that the present findings are important. We hope that our failure to detect menstrual cycle effects will encourage researchers to include women in their investigations of alcohol effects and human performance.

    View details for Web of Science ID 000170348900002

    View details for PubMedID 11523532

  • Rate of cognitive decline in AD is accelerated by the interleukin-1 alpha-889*1 allele NEUROLOGY Murphy, G. M., Claassen, J. D., DeVoss, J. J., Pascoe, N., Taylor, J., Tinklenberg, J. R., Yesavage, J. A. 2001; 56 (11): 1595-1597

    Abstract

    The reason for differences in rate of cognitive decline in AD is unknown. The interleukin-1 alpha (IL-1 alpha) -889 *2 allele is associated with increased risk for AD. Surprisingly, in a sample of 114 patients followed for an average of 3.8 years, individuals homozygous for the IL-1 alpha -889 *1 allele declined significantly more rapidly on the Mini-Mental State Examination than did others. There was no difference in rate of decline between patients with and without the APOE epsilon 4 allele. These results support the hypothesis that inflammation is important in the clinical course of AD.

    View details for Web of Science ID 000169187100033

    View details for PubMedID 11402127

  • Relationship between variations in estradiol and progesterone levels across the menstrual cycle and human performance PSYCHOPHARMACOLOGY Mumenthaler, M. S., O'Hara, R., Taylor, J. L., Friedman, L., Yesavage, J. A. 2001; 155 (2): 198-203

    Abstract

    Studies about whether or not the cognitive performance of women is influenced by changes in levels of sex steroid hormones across the menstrual cycle have produced ambiguous results.This study tested whether flight simulator performance differs significantly between the menstrual and the luteal phase of the menstrual cycle.In a within-subjects design, 24 female pilots were tested twice during their menstrual cycle: once during the menstrual and once during the luteal phase. On both test days they performed a 75-min simulator flight in a Frasca 141, a popular pilot training device.Despite highly significant differences in estradiol (E2) as well as progesterone (P) levels on the 2 test days, and despite excluding subjects with anovulatory cycles from the analyses, there were no significant differences in overall flight performance between the menstrual and luteal phases. We found no significant correlations between E2 or P levels and flight performance.We found no evidence that the tested menstrual cycle phases and their associated E2 and P levels significantly influence flight simulator performance. We consider these negative findings based on 24 subjects meaningful because previous studies on the influence of menstrual cycle on cognitive performance have not involved complex "real world" tasks such as piloting an aircraft and they obtained inconsistent results.

    View details for Web of Science ID 000168778000013

    View details for PubMedID 11401010

  • One year of insulin-like growth factor I treatment does not affect bone density, body composition, or psychological measures in postmenopausal women JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Friedlander, A. L., Butterfield, E., Moynihan, S., Grillo, J., Pollack, M., Holloway, L., Friedman, L., Yesavage, J., Matthias, D. F., Lee, S., Marcus, R., Hoffman, A. R. 2001; 86 (4): 1496-1503

    Abstract

    The activity of the hypothalamic-GH-insulin-like growth factor I (hypothalamic-GH-IGF-I) axis declines with age, and some of the catabolic changes of aging have been attributed to the somatopause. The purpose of this investigation was to determine the impact of 1 yr of IGF-I hormone replacement therapy on body composition, bone density, and psychological parameters in healthy, nonobese, postmenopausal women over 60 yr of age. Subjects (n = 16, 70.6 +/- 2.0 yr, 71.8 +/- 2.8 kg) were randomly assigned to either the self-injection IGF-I (15 microg/kg twice daily) or placebo group and were studied at baseline, at 6 months, and at 1 yr of treatment. There were no significant differences between the IGF-I and placebo groups in any of the measured variables at baseline. Fasting blood IGF-I levels were significantly elevated above baseline values (65.6 +/- 11.9 ng/mL) at 6 months (330.0 +/- 52.8) and 12 months (297.7 +/- 40.8) in the IGF-I treated group but did not change in the placebo subjects. Circulating levels of IGF-binding protein-1 and -3 were unaffected by the IGF-I treatment. Bone mineral density of the forearm, lumbar spine, hip, and whole body [as measured by dual-energy x-ray absorptiometry (DXA)] did not change in either group. Similarly, there was no difference in DXA-measured lean mass, fat mass, or percent body fat throughout the treatment intervention. Muscle strength values (grip, bench press, leg press), blood lipid parameters (cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides), and measures of postmeal glucose disposal were not altered by IGF-I treatment, although postmeal insulin levels were lower in the IGF-I subjects at 12 months. IGF-I did not affect bone turnover markers (osteocalcin and type I collagen N-teleopeptide), but subjects who were taking estrogen had significantly lower turnover markers than subjects who were not on estrogen at baseline, 6 months, and 12 months. Finally, the psychological measures of mood and memory were also not altered by the intervention. Despite the initial intent to recruit additional subjects, the study was discontinued after 16 subjects completed the protocol, because the preliminary analyses above indicated that no changes were occurring in any outcome variables, regardless of treatment regimen. Therefore, we conclude that 1 yr of IGF-I treatment, at a dose sufficient to elevate circulating IGF-I to young normal values, is not an effective means to alter body composition or blood parameters nor improve bone density, strength, mood, or memory in older women.

    View details for Web of Science ID 000168243000010

    View details for PubMedID 11297574

  • Event-related brain potential evidence of spared knowledge in Alzheimer's disease PSYCHOLOGY AND AGING Ford, J. M., Askari, N., Gabrieli, J. D., Mathalon, D. H., Tinklenberg, J. R., Menon, V., Yesavage, J. 2001; 16 (1): 161-176

    Abstract

    The authors recorded event-related brain potentials (ERPs) to picture primes and word targets (picture-name verification task) in patients with Alzheimer's disease (AD) and in elderly and young participants. N400 was more negative to words that did not match pictures than to words that did match pictures in all groups: In the young, this effect was significant at all scalp sites; in the elderly, it was only at central-parietal sites; and in AD patients, it was limited to right central-parietal sites. Among AD patients pretested with a confrontation-naming task to identify pictures they could not name, neither the N400 priming effect nor its scalp distribution was affected by ability to name pictures correctly. This ERP evidence of spared knowledge of these items was complemented by 80% performance accuracy. Thus, although the name of an item may be inaccessible in confrontation naming, N400 shows that knowledge is intact enough to prime cortical responses.

    View details for DOI 10.1037//0882-7974.16.1.161

    View details for Web of Science ID 000171004800014

    View details for PubMedID 11302364

  • Hearing impairment and serial word recall in older adults EXPERIMENTAL AGING RESEARCH Pearman, A., Friedman, L., Brooks, J. O., Yesavage, J. A. 2000; 26 (4): 383-391

    Abstract

    The objective of this work was to study the differences in performance on a nonauditory memory task between older volunteers with and without hearing impairment. The design was cross-sectional. Three-hundred-forty-four community-dwelling adults aged 55 to 93 years, who volunteered for a mnemonic training class served as participants. Participants' hearing was tested with a Maico MA-27 portable audiometer. The dependent measure was performance on a visually presented serial word recall test. Participants were also asked to report whether they had a problem with their hearing. Hearing impairment was associated with poor performance on a serial word recall task, even after controlling for age-related differences on that task. Hearing acuity appears to be related to serial word recall in older adults. Because auditory presentations were not involved, this relation raises the question of whether hearing loss may be concomitant with other changes that affect cognitive abilities.

    View details for Web of Science ID 000165086400008

    View details for PubMedID 11091943

  • Ethanol pharmacokinetics in white women: Nonlinear model fitting versus zero-order elimination analyses ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH Mumenthaler, M. S., Taylor, J. L., Yesavage, J. A. 2000; 24 (9): 1353-1362

    Abstract

    Studies have shown repeatedly that ethanol pharmacokinetics are not linear, yet most researchers still determine ethanol elimination by linear, zero-order kinetics. The goals of the present work were to: (1) fit four nonlinear pharmacokinetic models to mean breath alcohol concentration (BrAC)-time data of 27 women and determine the best-fit model; (2) fit the determined best-fit model to individual BrAC data and estimate the pharmacokinetic parameters; and (3) compare the method of nonlinear model fitting with the classical zero-order elimination method and determine in which cases the classical approach is justified.Twenty-seven healthy white women ingested four drinks (total of 0.67 g x kg(-1)) of ethanol on two test days. Approximately 24 breath ethanol samples (for pharmacokinetic analyses) and one blood sample (for hormonal markers) were taken per day. Pharmacokinetic model evaluation was based on the coefficient of variation, the weighted residual sum of squares, and the sequence of the weighted residuals. Because hormonal changes across the menstrual cycle did not significantly influence ethanol pharmacokinetics, data from the two test days were pooled.The best-fit model was a one-compartment open model with first-order absorption and sequential first-order elimination, followed by Michaelis-Menten elimination kinetics. Fitting this model to the individual BrAC data yielded mean ka = 0.062 hr(-1), Vd = 0.457 L x kg(-1), ke = 0.011 hr(-1), Vmax = 0.136 g x L(-1) x hr(-1), and Km = 0.096 g x L(-1). For the classical analyses, mean time to peak BrAC = 1.83 hr, disappearance rate = 0.179 g x L(-1) x hr(-1), and area under the blood ethanol-time curve (AUC) = 2.884 g x L(-1) x hr. Correlational analyses showed that more frequent drinkers eliminated ethanol significantly faster and reached significantly lower AUC than less frequent drinkers.After multiple dose ingestion in white women, classical zero-order elimination analyses can be applied only to a limited portion of the descending BrAC-time curve. They seem justified and practical from 0.5 hr after peak BrAC until BrAC reaches 0.2 g x L(-1). To describe ethanol pharmacokinetics across the entire BrAC-time curve, however, sophisticated nonlinear model fitting is required.

    View details for Web of Science ID 000089364800005

    View details for PubMedID 11003200

  • A retrospective chart review of gabapentin for the treatment of aggressive and agitated behavior in patients with dementias AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Hawkins, J. W., Tinklenberg, J. R., Sheikh, J. I., PEYSER, C. E., Yesavage, J. A. 2000; 8 (3): 221-225

    Abstract

    In a 24-patient case series from retrospective chart review, the authors examined the use of gabapentin for the treatment of aggressive and agitated behaviors in nursing home patients with a DSM-IV diagnosis of dementia. On Clinical Global Rating Scale scores, 17 of 22 patients were much or greatly improved; 4 were minimally improved; and only 1 remained unchanged. Two of the 24 patients discontinued use of the medication because of excessive sedation. No other significant side effects were noted in treatment lasting up to 2 years.

    View details for Web of Science ID 000088230700007

    View details for PubMedID 10910420

  • A longitudinal study of Apolipoprotein-E genotype and depressive symptoms in community-dwelling older adults AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Mauricio, M., O'Hara, R., Yesavage, J. A., FRIEDMAN, E., Kraemer, H. C., Van de Water, M., Murphy, G. M. 2000; 8 (3): 196-200

    Abstract

    The Apolipoprotein-E (APOE) epsilon 4 allele is a risk factor for Alzheimer's disease (AD) and cognitive decline in older adults. Depression may also be a risk factor for dementia, and depression is important in the differential diagnosis of dementia. The authors performed a 5-year longitudinal study of APOE genotype and change in Geriatric Depression Scale scores in 113 community-dwelling older adults. No association was observed between APOE genotype and change in depressive symptoms. These results do not support the hypothesis that the APOE epsilon 4 allele is associated with depression. Important objections have been raised to APOE genotyping in the diagnosis of AD. However, the specificity of APOE genotyping in AD diagnosis would not appear to be compromised by an association with depression.

    View details for Web of Science ID 000088230700003

    View details for PubMedID 10910416

  • Combined assessment of tau and neuronal thread protein in Alzheimer's disease CSF NEUROLOGY Kahle, P. J., Jakowec, M., Teipel, S. J., Hampel, H., Petzinger, G. M., Di Monte, D. A., Silverberg, G. D., Moller, H. J., Yesavage, J. A., Tinklenberg, J. R., Shooter, E. M., Murphy, G. M. 2000; 54 (7): 1498-1504

    Abstract

    Comparative study of CSF levels of tau and AD7C-neuronal thread protein (NTP) in patients with AD and control subjects.AD is characterized by neurofibrillary tangles composed of the abnormally hyperphosphorylated microtubule-associated protein tau. AD7C-NTP is a proposed AD marker expressed at early stages of neurofibrillary degeneration.Enzyme-linked immunosorbent assays specific for tau and AD7C-NTP. CSF samples were obtained from 35 demented patients (25 with antemortem clinical diagnosis of probable AD, 5 with neuropathologic diagnosis of definite AD, 5 with Lewy body pathology), 29 nondemented patients with PD, and 16 elderly healthy control subjects. Receiver operating characteristics (ROC) and multivariate discriminant analysis for AD versus controls. Correlational analysis of CSF tau and AD7C-NTP and of each marker with Mini-Mental State Examination (MMSE) scores was performed.Levels of both tau and AD7C-NTP were significantly elevated in the AD patients compared with control subjects. ROC analysis showed that CSF tau distinguished between patients with AD and nondemented control subjects with 63% sensitivity and 89% specificity, AD7C-NTP with 70% sensitivity and 87% specificity. Combined evaluation of both markers with discriminant analysis raised the specificity to 93% at a 63% sensitivity level. Both markers positively correlated with each other within the AD group, but not among control subjects. CSF levels of AD7C-NTP, but not of tau, showed a small but significant inverse correlation (r = -0.43) with MMSE scores of AD patients.CSF levels of tau and AD7C-NTP may be useful biomarkers for AD.

    View details for Web of Science ID 000086460900021

    View details for PubMedID 10751266

  • Relationship of CogScreen-AE to flight simulator performance and pilot age AVIATION SPACE AND ENVIRONMENTAL MEDICINE Taylor, J. L., O'Hara, R., Mumenthaler, M. S., Yesavage, J. A. 2000; 71 (4): 373-380

    Abstract

    We report on the relationship between CogScreen-Aeromedical Edition (AE) factor scores and flight simulator performance in aircraft pilots aged 50-69.Some 100 licensed, civilian aviators (average age 58+/-5.3 yr) performed aviation tasks in a Frasca model 141 flight simulator and the CogScreen-AE battery. The aviation performance indices were: a) staying on course; b) dialing in communication frequencies; c) avoiding conflicting traffic; d) monitoring cockpit instruments; e) executing the approach; and f) a summary score, which was the mean of these scores. The CogScreen predictors were based on a factor structure reported by Kay (11), which comprised 28 CogScreen scores. Through principal components analysis of Kay's nine factors, we reduced the number of predictors to five composite CogScreen scores: Speed/Working Memory (WM), Visual Associative Memory, Motor Coordination, Tracking, and Attribute Identification.Speed/WM scores had the highest correlation with the flight summary score, Spearman r(rho) = 0.57. A stepwise-forward multiple regression analysis indicated that four CogScreen variables could explain 45% of the variance in flight summary scores. Significant predictors, in order of entry, were: Speed/WM, Visual Associative Memory, Motor Coordination, and Tracking (p<0.05). Pilot age was found to significantly improve prediction beyond that which could be predicted by the four cognitive variables. In addition, there was some evidence for specific ability relationships between certain flight component scores and CogScreen scores, such as approach performance and tracking errors.These data support the validity of CogScreen-AE as a cognitive battery that taps skills relevant to piloting.

    View details for Web of Science ID 000086061300002

    View details for PubMedID 10766461

  • An actigraphic comparison of sleep restriction and sleep hygiene treatments for insomnia in older adults JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Friedman, L., Benson, K., Noda, A., Zarcone, V., Wicks, D. A., O'Connell, K., Brooks, J. O., Bliwise, D. L., Yesavage, J. A. 2000; 13 (1): 17-27

    Abstract

    We compared the efficacy of sleep restriction therapy combined with sleep hygiene, nap modification of sleep restriction therapy combined with sleep hygiene, and sleep hygiene alone as treatments for insomnia in 39 community-dwelling men and women 55 years and older. We used the wrist actigraph as an objective outcome measure for all subjects at baseline, end of treatment, and 3-month follow-up; polysomnography (PSG) was conducted in a subgroup of subjects. Although subjects appeared to follow restriction instructions through follow-up, we found few between-group differences in treatment efficacy. Lack of treatment effect might be explained by the efficacy of HYG as a treatment in itself and the relatively low symptom level in these healthy older poor sleepers. At baseline, actigraphic results were found to correlate more highly than sleep log data with PSG in our sample. Actigraphic total sleep time, in particular, was highly correlated with PSG.

    View details for Web of Science ID 000085979100003

    View details for PubMedID 10753003

  • Update on Alzheimer's disease: recent findings and treatments WESTERN JOURNAL OF MEDICINE O'Hara, R., Mumenthaler, M. S., Yesavage, J. A. 2000; 172 (2): 115-120

    View details for Web of Science ID 000085217100020

    View details for PubMedID 10693374

  • How can we learn about developmental processes from cross-sectional studies, or can we? AMERICAN JOURNAL OF PSYCHIATRY Kraemer, H. C., Yesavage, J. A., Taylor, J. L., Kupfer, D. 2000; 157 (2): 163-171

    Abstract

    Cross-sectional studies are often used in psychiatric research as a basis of longitudinal inferences about developmental or disease processes. While the limitations of such usage are often acknowledged, these are often understated. The authors describe how such inferences are often, and sometimes seriously, misleading.Why and how these inferences mislead are here demonstrated on an intuitive level, by using simulated data inspired by real problems in psychiatric research.Four factors with major roles in the relationship between cross-sectional studies and longitudinal inferences are selection of time scale, type of developmental process studied, reliability of measurement, and clarity of terminology. The authors suggest how to recognize inferential errors when they occur, describe how to protect against such errors in future research, and delineate the circumstances in which only longitudinal studies can answer crucial questions.The simple conclusion is that one must always use the results of cross-sectional studies to draw inferences about longitudinal processes with trepidation.

    View details for Web of Science ID 000085169000003

    View details for PubMedID 10671382

  • Convergent behavioral and neuropsychological evidence for a distinction between identification and production forms of repetition priming JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL Gabrieli, J. D., Vaidya, C. J., Stone, M., Francis, W. S., Thompson-Schill, S. L., Fleischman, D. A., Tinklenberg, J. R., Yesavage, J. A., Wilson, R. S. 1999; 128 (4): 479-498

    Abstract

    Four experiments examined a distinction between kinds of repetition priming which involve either the identification of the form or meaning of a stimulus or the production of a response on the basis of a cue. Patients with Alzheimer's disease had intact priming on picture-naming and category-exemplar identification tasks and impaired priming on word-stem completion and category-exemplar production tasks. Division of study-phase attention in healthy participants reduced priming on word-stem completion and category-exemplar production tasks but not on picture-naming and category-exemplar identification tasks. The parallel dissociations in normal and abnormal memory cannot be explained by implicit-explicit or perceptual-conceptual distinctions but are explained by an identification-production distinction. There may be separable cognitive and neural bases for implicit modulation of identification and production forms of knowledge.

    View details for Web of Science ID 000084711800004

    View details for PubMedID 10650584

  • Dissociation between two forms of conceptual priming in Alzheimer's disease NEUROPSYCHOLOGY Vaidya, C. J., Gabrieli, J. D., Monti, L. A., Tinklenberg, J. R., Yesavage, J. A. 1999; 13 (4): 516-524

    Abstract

    Patients with Alzheimer's disease (AD) and healthy control participants performed 2 conceptual repetition priming tasks, word-associate production and category-exemplar production. Both tasks had identical study-phases of reading target words aloud, had the most common responses as target items, and required production of a single response. Patients with AD showed normal priming on word-associate production but impaired priming on category-exemplar production. This dissociation in AD suggests that conceptual priming is not a unitary form of memory but rather is mediated by separable memory systems.

    View details for Web of Science ID 000083035700005

    View details for PubMedID 10527059

  • Predicting response of older adults to mnemonic training: who will benefit? International psychogeriatrics MCKITRICK, L. A., Friedman, L. F., Brooks, J. O., Pearman, A., Kraemer, H. C., Yesavage, J. A. 1999; 11 (3): 289-300

    Abstract

    To identify profiles of subjects who respond to mnemonic training for serial word and proper name recall.Analysis of J. O. Brooks et al.'s (1999) mnemonic training data using Quality Receiver Operating Characteristic (QROC) and longitudinal regression analyses (LRA).Community.224 community-dwelling adults 55 years of age and older who wished to improve their memory.Performance on serial word and proper name tests; performance on cognitive ability tests.Although the QROC and LRA identified several common predictors (baseline performance, mental rotation ability, and paired associate learning), the QROC identified additional predictors and cognitive ability profiles associated with successful response.Similar degrees of response to mnemonic training are associated with heterogeneous cognitive profiles. This finding highlights the fact that participants rely on a variety of abilities to derive benefit from mnemonic training and thus suggests different avenues from which to approach this training.

    View details for PubMedID 10547129

  • Relationship of age and simulated flight performance JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Yesavage, J. A., Taylor, J. L., Mumenthaler, M. S., Noda, A., O'Hara, R. 1999; 47 (7): 819-823

    Abstract

    To determine the relationship between age and aviator performance on a flight simulator.A cross-sectional observational study.The sample consisted of 100 aviators aged 50 to 69 (mean = 58).Pilots were tested on a Frasca 141 flight simulator (Urbana, IL), linked to a UNIX-based IRIS 4D computer (Silicon Graphics, Mountain View, CA), which both generated graphics of the environment in which the pilots flew and collected data concerning the aircraft's flight conditions.We found that increased age was significantly associated with decreased aviator performance on a flight simulator.Although there was a significant relationship between increased age and decreased aviator performance, age explained 22% or less of the variance of performance on different flight tasks; hence, other factors are also important in explaining the performance of older pilots.

    View details for Web of Science ID 000081323400007

    View details for PubMedID 10404925

  • Mnemonic training in older adults: effects of age, length of training, and type of cognitive pretraining. International psychogeriatrics Brooks, J. O., Friedman, L., Pearman, A. M., Gray, C., Yesavage, J. A. 1999; 11 (1): 75-84

    Abstract

    To improve performance with mnemonic techniques for remembering words and proper names.For word recall, a 2 x 2 factorial in which type of pretraining and length of training were between-subjects manipulations. For proper name recall, a two-group design in which type of pretraining was manipulated between subjects.Community.268 community-dwelling adults over the age of 55 years who wished to improve their memory.Recall of words and proper names both before and after training in mnemonics.Participants received a 2-week training course on two mnemonic techniques, the method of loci for words and a name association technique for proper names.There was no effect of the pretraining manipulation on proper name recall. For word recall, however, a multiple regression that included age indicated that the older-old participants benefited more from a combination of comprehensive pretraining and extended mnemonic training than did the younger-old.Increased training time coupled with a comprehensive pretraining regimen can improve the performance of the older-old in using mnemonics; this improved performance cannot be attributed solely to enhanced knowledge of the mnemonic.

    View details for PubMedID 10189601

  • How to drastically reduce priming in word stem completion and still present the words MEMORY & COGNITION Brooks, J. O., Gibson, J. M., Friedman, L., Yesavage, J. A. 1999; 27 (2): 208-219

    Abstract

    This paper describes a series of experiments in which we demonstrated that "dysphonemic" word stems, which are likely not pronounced in isolation as they are within a word (e.g., MUS in MUSHROOM or LEG in LEGEND), showed less priming than did "phonemic stems" (e.g., MUS in MUSTARD or LEG in LEGACY). Furthermore, words with either dysphonemic or phonemic three-letter stems gave rise to equivalent levels of priming when test cues were four-letter stems (LEGE) or word fragments (L_G_ND). Moreover, the difference between phonemic and dysphonemic stems persisted when nonpresented completion rates were matched. A final cued-recall experiment revealed that performance was greater for phonemic stems than for dysphonemic stems and that this difference was greater for older participants than for younger ones. These results are not readily accounted for by extant theoretical approaches and point to important methodological issues regarding stem completion.

    View details for Web of Science ID 000079821600002

    View details for PubMedID 10226432

  • Geriatric performance on the Benton visual retention test: demographic and diagnostic considerations CLINICAL NEUROPSYCHOLOGIST Coman, E., Moses, J. A., Kraemer, H. C., Friedman, L., Benton, A. L., Yesavage, J. 1999; 13 (1): 66-77

    Abstract

    We examined relationships between demographic and diagnostic variables and Benton Visual Retention Test performance in older adults aged 55 to 97 years. We derived extended geriatric norms for BVRT total number correct scores adjusted for variables that contributed significantly to the variance. We also investigated BVRT performance in two commonly presenting diagnostic groups: (1) normal adults with memory concerns, and (2) a group with mixed neurologic disorders. Age and education but not gender were significantly associated with BVRT performance in both normals and normals with memory concerns. Level of cognitive deficit was a moderating factor in that age and education also contributed significantly to the BVRT performance of no/low deficit neurologic patients but had no impact in patients whose cognitive deficits were moderate/severe.

    View details for Web of Science ID 000082002000007

    View details for PubMedID 10937649

  • Effects of menstrual cycle and female sex steroids on ethanol pharmacokinetics ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH Mumenthaler, M. S., Taylor, J. L., O'Hara, R., Fisch, H. U., Yesavage, J. A. 1999; 23 (2): 250-255

    Abstract

    This study investigated the influence of menstrual cycle and female sex steroid levels on ethanol pharmacokinetics. In a within-subjects design, 24 female volunteers each consumed 0.67 g x kg(-1) ethanol during the menstrual and luteal phases of their menstrual cycle. On each test day, we collected blood samples before ethanol administration to determine estradiol (E2) and progesterone (P) levels and to confirm ovulation. We took 20 or more postdrink breath ethanol concentration readings and examined pharmacokinetic differences between the two phases, using classical pharmacokinetic measures, as well as Michaelis-Menten measures. Despite highly significant differences in measured E2 as well as P levels on the 2 test days, and despite excluding subjects with anovulatory cycles from the analysis, there were no significant differences between menstrual and luteal phases for any of the pharmacokinetic variables. We found no correlation between E2 or P levels and any of the pharmacokinetic measures. In summary, we found no evidence that the tested menstrual cycle phases or varying E2 and progesterone levels significantly influence ethanol pharmacokinetics. Because previous studies about the topic have used few subjects and revealed controversial results, we consider our negative findings based on 24 subjects meaningful.

    View details for Web of Science ID 000078678700009

    View details for PubMedID 10069553

  • Gender differences in moderate drinking effects ALCOHOL RESEARCH & HEALTH Mumenthaler, M. S., Taylor, J. L., O'Hara, R., Yesavage, J. A. 1999; 23 (1): 55-?

    Abstract

    Women appear to become more impaired than men after drinking equivalent amounts of alcohol, achieving higher blood alcohol concentrations even when doses are adjusted for body weight. This finding may be attributable in part to gender differences in total body water content. Men and women appear to eliminate approximately the same total amount of alcohol per unit body weight per hour. However, women seem to eliminate significantly more alcohol per unit of lean body mass per hour than men. Some studies report that women are more susceptible than men to alcohol-related impairment of cognitive performance, especially in tasks involving delayed memory or divided attention functions. Psychomotor performance impairment, however, does not appear to be affected by gender. This article provides an overview of alcohol metabolism (pharmacokinetics) and reviews recent studies on gender differences in alcohol absorption, distribution, elimination, and impairment. Speculation that gender differences in alcohol pharmacokinetics or alcohol-induced performance impairment may be caused by the menstrual cycle and variations in female sex hormones are discussed. It is concluded that the menstrual cycle is unlikely to influence alcohol pharmacokinetics.

    View details for Web of Science ID 000084105600008

    View details for PubMedID 10890798

  • The APOE epsilon 4 allele is associated with decline on delayed recall performance in community-dwelling older adults JOURNAL OF THE AMERICAN GERIATRICS SOCIETY O'Hara, R., Yesavage, J. A., Kraemer, H. C., Mauricio, M., Friedman, L. F., Murphy, G. M. 1998; 46 (12): 1493-1498

    Abstract

    This study investigated whether the Apolipoprotein (APOE) epsilon4 allele was associated with cognitive decline in community-dwelling older adults.Longitudinal cognitive performance of older adults with the epsilon3/epsilon4 genotype was compared with that of older adults with the epsilon3/epsilon3 genotype.Aging Clinical Research Center, Stanford University.One hundred community-dwelling older adults were recruited from a pool of 531 individuals who had participated in a memory training study 4 to 5 years earlier. These individuals were concerned about their memory functioning and were recruited through newspaper advertisements and contacts with local senior centers. The 100 individuals who agreed to participate in the follow-up investigation were between 59 and 95 years of age.At both baseline and follow-up, subjects were administered a battery of seven cognitive tests that examined verbal and spatial memory, attention, speed-of-processing, and language abilities. APOE genotype was determined at follow-up.Individuals with the epsilon3/epsilon4 APOE genotype were significantly younger than individuals with the APOE epsilon3/epsilon3 genotype. No significant differences were observed between the two groups on measures of attention, speed-of-processing, vocabulary, immediate verbal memory, and immediate spatial memory. However, those older adults with the epsilon3/epsilon4 genotype exhibited significantly greater decline in performance on delayed recall of verbal material than did those with the epsilon3/epsilon3 APOE genotype.These findings are consistent with previous studies, which suggest that the APOE epsilon4 allele predicts decline on measures of delayed recall.

    View details for Web of Science ID 000077358700001

    View details for PubMedID 9848808

  • The stages of Alzheimer's disease: A reappraisal DEMENTIA AND GERIATRIC COGNITIVE DISORDERS Kraemer, H. C., Taylor, J. L., Tinklenberg, J. R., Yesavage, J. A. 1998; 9 (6): 299-308

    Abstract

    'Stages', as used in clinical practice and research, are defined, their value described, and criteria are proposed for their evaluation. The specific interest is in staging Alzheimer's disease (AD). Two staging systems, one based on the Global Deterioration Scale (GDS) and one based on the Mini-Mental State Exam (MMSE), are compared in terms of these criteria, as an illustration of the process involved. We propose that there is not one unique staging system, that different staging criteria might be appropriate to different research or clinical needs, depending on which part of the temporal course of the disease is of primary interest, and on whether the focus is on cognitive, functional, neurological, behavioral, economic, or other issues. GDS staging seems a better choice for the later stages of AD when the focus is on functional change. MMSE staging seems a better choice for tracking the earlier stages of AD when the focus is on cognitive change.

    View details for Web of Science ID 000076711600001

    View details for PubMedID 9769442

  • Influence of nicotine on simulator flight performance in non smokers PSYCHOPHARMACOLOGY Mumenthaler, M. S., Taylor, J. L., O'Hara, R., Yesavage, J. A. 1998; 140 (1): 38-41

    Abstract

    In a placebo-controlled study, we investigated the influence of nicotine on late-day aviation performance in 15 non-smoking subjects. In a within-subjects design, subjects were tested on 2 days, each lasting 8 h and consisting of three 75-min simulator flights (late-afternoon practice, evening test, night test). Prior to each test, subjects received either nicotine polacrilex 2 mg or placebo gum. As expected, overall performance was significantly better after nicotine, compared to placebo (P < 0.01). Post-hoc analysis of individual flight tasks showed that nicotine improved scores on approach to landing, a task which appears to require sustained attention. We conclude that nicotine may improve late-day flight performance in non-smoking aviators.

    View details for Web of Science ID 000077151700005

    View details for PubMedID 9862400

  • Preserved priming across study-test picture transformations in patients with Alzheimer's disease NEUROPSYCHOLOGY Park, S. M., Gabrieli, J. D., Reminger, S. L., Monti, L. A., Fleischman, D. A., Wilson, R. S., Tinklenberg, J. R., Yesavage, J. A. 1998; 12 (3): 340-352

    Abstract

    Picture-naming priming was examined across different study-test transformations to explore the nature of memory representations of objects supporting implicit memory processes in patients with Alzheimer's disease (AD). Although severely impaired in explicit memory for pictures and words, AD patients demonstrated normal priming across perceptual transformations in picture orientation (Experiment 1) and picture size (Experiment 2) and across symbolic transformations from words to pictures (Experiment 3). In addition, the priming across alterations in picture size was invariant. This demonstrates that AD patients have preserved implicit memory for high-level, abstract representations of objects.

    View details for Web of Science ID 000074744800002

    View details for PubMedID 9673992

  • Acetyl L-carnitine slows decline in younger patients with Alzheimer's disease: a reanalysis of a double-blind, placebo-controlled study using the trilinear approach. International psychogeriatrics Brooks, J. O., Yesavage, J. A., Carta, A., Bravi, D. 1998; 10 (2): 193-203

    Abstract

    To assess the longitudinal effects of acety-L-carnitine (ALC) on patients diagnosed with Alzheimer's disease.Longitudinal, double-blind, parallel-group, placebo-controlled.Twenty-four outpatient sites across the United States.A total of 334 subjects diagnosed with probable Alzheimer's disease by NINCDS-ADRDA criteria. These data were originally reported by Thal and colleagues (1996).Cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) given every 3 months for 1 year.The average rate of change was estimated using the trilinear approach, which allows for periods of both change and stability. Both the ALC group and the placebo group exhibited the same mean rate of change on the ADAS (0.68 points/month). However, a multiple regression analysis revealed a statistically significant Age x Drug interaction characterized by younger subjects benefiting more from ALC, significant, cutpoint for ALC benefit was 61 years of age.ALC slows the progression of Alzheimer's disease in younger subjects, and the use of the trilinear approach to estimate the average rate of change may prove valuable in pharmacological trials.

    View details for PubMedID 9677506

  • A follow-up study of actigraphic measures in home-residing Alzheimer's disease patients JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY Yesavage, J. A., Friedman, L., Kraemer, H. C., Noda, A., Wicks, D., Bliwise, D. L., Sheikh, J., Tinklenberg, J., Zarcone, V. 1998; 11 (1): 7-10

    Abstract

    This article reports cross-sectional and follow-up data with actigraphic measures of nocturnal sleep and rest/activity in 61 Alzheimer's disease (AD) patients as well as the relation of actigraphic measures to levels of behavioral disturbance across different stages of the disease. Over the course of approximately 1.5 years' follow-up, patients showed significant deterioration of nocturnal sleep parameters, but no significant change in rest/activity circadian rhythm parameters. There were also significant correlations among nocturnal sleep, rest/activity circadian rhythm, and behavioral disturbance measures, but only in relatively early stages of AD. It is argued that study of nocturnal sleep and circadian rhythm in relation to behavioral disturbance in AD requires longitudinal data and analyses that take into account the stage of disease at which patients are assessed.

    View details for Web of Science ID 000074755600002

    View details for PubMedID 9686746

  • Adjusting Mini-Mental State Examination scores for age and educational level to screen for dementia: correcting bias or reducing validity? International psychogeriatrics Kraemer, H. C., MORITZ, D. J., Yesavage, J. 1998; 10 (1): 43-51

    Abstract

    The question of whether Mini-Mental State Examination scores should be adjusted for age and educational levels to screen for dementia in clinical populations is reexamined in the results of a recent study supporting adjustment. If the criterion is to identify the most accurate screening procedure for each sociodemographic subgroup, the evidence indicates that the unadjusted scores are preferable. Other criteria might lead to different conclusions. The validities of some of these criteria are questionable because they have the flaw that they are easily satisfied by using random decision procedures.

    View details for PubMedID 9629523

  • Structural MRI correlates of recognition memory in Alzheimer's disease JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY Cahn, D. A., SULLIVAN, E. V., Shear, P. K., Marsh, L., Fama, R., Lim, K. O., Yesavage, J. A., Tinklenberg, J. R., Pfefferbaum, A. 1998; 4 (2): 106-114

    Abstract

    Neuroimaging and lesion studies have demonstrated that hippocampal volume correlates with memory performance, but material-specific lateralization of this structure-function relationship has been inconsistent. This MRI study examined the relative contributions of left and right temporal lobe volumes to verbal and nonverbal recognition memory in a group of 20 Alzheimer's disease (AD) patients. There was a significant relationship between extent of right hippocampal and right temporal gray matter tissue volume deficit and performance on the face recognition subtest of the Warrington Recognition Memory Test. The face recognition test correlated with right hemisphere volume but not to left, indicating a material-specific relationship between brain structure and function in this patient group. Right temporal horn volume did not account for a significant proportion of variance in face recognition memory. Although word recognition was not significantly correlated with either left or right hippocampal volume in the total group, there was a strong correlation between left hippocampal volume and word recognition memory in the female AD patients. Thus, face recognition shows a material specific relationship with select lateralized hippocampal and temporal cortical volumes in AD patients, regardless of gender, whereas the verbal recognition-left-hippocampal volume relationship may be mediated by gender.

    View details for Web of Science ID 000075146200002

    View details for PubMedID 9529820

  • No association between apolipoprotein E epsilon 4 allele and rate of decline in Alzheimer's disease AMERICAN JOURNAL OF PSYCHIATRY Murphy, G. M., Taylor, J., Kraemer, H. C., Yesavage, J., Tinklenberg, J. R. 1997; 154 (5): 603-608

    Abstract

    The relationship between number of apolipoprotein E epsilon 4 (APOE epsilon 4) alleles and the rate of cognitive decline in patients with Alzheimer's disease was examined.Rate of decline in score on the Mini-Mental State was measured during the active phase of the decline curve between Mini-Mental State scores of 23 and 0. To characterize onset, the authors also estimated for each subject the age at which the Mini-Mental State score fell below 23 and obtained a retrospective report of age at onset from the caregiver. The number of APOE epsilon 4 alleles carried by each subject was determined from genomic DNA samples. The study included 86 subjects with probable Alzheimer's disease who had had at least two cognitive evaluations (a mean of 5.6 evaluations per subject over an average period of 3.6 years).The results did not support an association between APOE epsilon 4 dosage and rate of cognitive decline. Age at onset and age at which the Mini-Mental State score fell below 23 were also not related to APOE epsilon 4 dosage. The APOE allele frequencies were similar to those in other studies of subjects with Alzheimer's disease, showing an enrichment of the epsilon 4 allele.Although the APOE epsilon 4 allele is a risk factor for Alzheimer's disease, there is no support of a strong association between APOE epsilon 4 dosage and rate of cognitive decline. The epsilon 4 allele did not predict age at onset. Methodological inconsistencies may account for discrepancies between these results and previous findings.

    View details for Web of Science ID A1997WX13000004

    View details for PubMedID 9137113

  • No association between the alpha 1-antichymotrypsin A allele and Alzheimer's disease NEUROLOGY Murphy, G. M., SULLIVAN, E. V., GALLAGHERTHOMPSON, D., Thompson, L. W., vanDuijn, C. M., Forno, L. S., Ellis, W. G., Jagust, W. J., Yesavage, J., Tinklenberg, J. R. 1997; 48 (5): 1313-1316

    Abstract

    The alpha 1-antichymotrypsin (ACT) A allele was recently associated with Alzheimer's disease (AD), and the ACT AA genotype was reported to be more frequent in AD subjects with the apolipoprotein E (APOE) epsilon4 allele. We examined ACT and APOE genotypes in a sample of 160 subjects with probable AD and in 102 elderly control subjects. ACT A allele frequencies were similar in AD subjects (0.503) and elderly controls (0.519). In addition, we found no evidence that in AD the AA genotype is more frequent in subjects with the APOE epsilon4 allele than in those without it. Our results do not support an association between the ACT A allele and AD.

    View details for Web of Science ID A1997WZ77800030

    View details for PubMedID 9153464

  • Automatic and effortful processing in aging and dementia: Event-related brain potentials NEUROBIOLOGY OF AGING Ford, J. M., Roth, W. T., Isaacks, B. G., Tinklenberg, J. R., Yesavage, J., Pfefferbaum, A. 1997; 18 (2): 169-180

    Abstract

    Automatic and effortful processes were investigated using event-related brain potentials (ERPs) recorded from moderately impaired subjects with probable Alzheimer's Disease (AD), normal elderly, and normal young controls. The effects of effortful attention on ERPs to loud noises and the effects of stimulus intrusiveness on effortfully elicited ERPs were studied. First, ERPs to task relevant and irrelevant startling noises were compared. Second, ERPs to startling noises and moderate tones were compared when both were targets. The effects of age (young vs. elderly controls) and effects of dementing disease (AD subjects vs. elderly controls) were also assessed. Effortful attention augmented noise-elicited P300 amplitude in elderly subjects, but not in young. Intrusiveness augmented task-relevant P300 amplitude in young subjects, but not in elderly. Neither variable affected P300 amplitude in AD subjects. Thus, effects of age and disease depended on how P300 was elicited: when effortfully elicited, P300 amplitude was affected by disease but not age; when automatically elicited, P300 amplitude was affected by age but not disease. N1 effects differed from P300 effects.

    View details for Web of Science ID A1997XP01300006

    View details for PubMedID 9258894

  • The apolipoprotein E epsilon 4 allele is associated with increased behavioral disturbance in Alzheimer's disease AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Murphy, G. M., Taylor, J., Tinklenberg, J. R., Yesavage, J. A. 1997; 5 (1): 88-89

    View details for Web of Science ID A1997VZ64200012

    View details for PubMedID 9169250

  • Rate of cognitive decline in Alzheimer's disease is not affected by the alpha-1-antichymotrypsin A allele or the CYP2D6 B mutant NEUROSCIENCE LETTERS Murphy, G. M., Yang, L., Yesavage, J., Tinklenberg, J. R. 1996; 217 (2-3): 200-202

    Abstract

    Patients with Alzheimer's disease (AD) show considerable heterogeneity in the rate at which they decline cognitively. The biological basis for this heterogeneity is unknown. We genotyped 86 subjects with diagnoses of probable AD to determine if they carried the alpha-1-antichymotrypsin (ACT) A allele, which has been associated with AD, or the CYP2D6 B mutant, found at increased frequency in the Lewy body variant (LBV) of AD. We then examined longitudinally-collected cognitive data to determine if these genetic markers were associated with rate of cognitive decline. Our results indicate that neither the ACT A allele nor the CYP2D6 B allele have a significant association with rate of decline on the Folstein Mini Mental State examination. Further, subjects with both the ACT A allele and the apolipoprotein epsilon 4 allele showed no evidence of accelerated decline. These findings suggest that any increased risk of developing AD or LBV conferred by these markers is not necessarily accompanied by a more rapid rate of decline.

    View details for Web of Science ID A1996VQ39800033

    View details for PubMedID 8916107

  • PERCEPTIONS OF LIFE STRESS AND CHRONIC INSOMNIA IN OLDER ADULTS PSYCHOLOGY AND AGING Friedman, L., Brooks, J. O., Bliwise, D. L., Yesavage, J. A., WICKS, D. S. 1995; 10 (3): 352-357

    Abstract

    This study compared the level of self-reported stress of 42 older good sleepers (M age = 68.2 years) and 42 poor sleepers (M age = 68.7 years). The relations among subjective ratings of sleep, level of perceived stress, and negative mood were analyzed for each group. Good and poor sleepers reported similar amounts of life stress, but the relations between life stress and sleep perceptions differed for the 2 groups. Specifically, within the group of poor sleepers, those with higher life stress had greater difficulty falling asleep and less early morning waking than did poor sleepers with lower life stress. There was no association between life stress and any sleep measures for good sleepers. These results are compatible with the notion that good and poor sleepers may have different susceptibilities to poor sleep despite experiencing similar stressful life events.

    View details for Web of Science ID A1995RV98000005

    View details for PubMedID 8527056

  • LONGITUDINAL VOLUMETRIC COMPUTED TOMOGRAPHIC ANALYSIS OF REGIONAL BRAIN CHANGES IN NORMAL AGING AND ALZHEIMERS-DISEASE ARCHIVES OF NEUROLOGY Shear, P. K., SULLIVAN, E. V., Mathalon, D. H., Lim, K. O., Davis, L. F., Yesavage, J. A., Tinklenberg, J. R., Pfefferbaum, A. 1995; 52 (4): 392-402

    Abstract

    This study used a semiautomated image analysis technique to quantify the rate and regional pattern of cerebrospinal fluid (CSF) volume changes in the computed tomographic brain examinations of healthy adults and patients with Alzheimer's disease (AD).Longitudinal, within-subject design, with statistical correction for longitudinal method error (eg, head repositioning effects).Palo Alto (Calif) Department of Veterans Affairs Medical Center.The 41 patients with AD were recruited from the Geriatric Psychiatry Research Unit and the National Institute of Mental Health Clinical Research Center of the Palo Alto Department of Veterans Affairs Medical Center. The 35 healthy control subjects were recruited from the local community.Cerebrospinal fluid volumes estimated from computed tomographic scans.Even after accounting for an estimate of method error (eg, head positioning effects) across computed tomographic examinations, the patients with AD showed greater annual CSF volume increases than did the control group. This CSF volume enlargement was not uniform across brain regions of interest; rather, the patients with AD showed disproportionate volume increases in the ventricular system and the sylvian fissures. Greater CSF volume changes in the patients with AD were significantly associated with greater cognitive decline on the Mini-Mental State Examination. Furthermore, younger patients with AD showed more rapid progression on computed tomographic scans than did older patients.The rate of CSF volume enlargement is region specific, with the most marked annual rate of change occurring in the ventricular system and the sylvian fissures. In addition, younger patients show more rapid progression in the ventricular and frontal sulcal brain regions of interest than do older patients.

    View details for Web of Science ID A1995QR98600014

    View details for PubMedID 7710375

  • FLIGHT SIMULATOR PERFORMANCE OF YOUNGER AND OLDER AIRCRAFT PILOTS - EFFECTS OF AGE AND ALCOHOL JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Yesavage, J. A., DOLHERT, N., Taylor, J. L. 1994; 42 (6): 577-582

    Abstract

    To determine if older pilots forgot more about a learned flight task after a 10-month delay than did younger pilots and if the anticipated greater skill loss led older pilots' performance to be more disrupted by alcohol.Repeated measures comparative group design examining the effects of alcohol versus placebo in two age groups (younger and older) and at two timepoints: acute intoxication, at a Blood Alcohol Concentration (BAC) of 0.10%, and 8 hours post-drink.University medical center research laboratory.Fourteen younger (mean age = 27; SD = 4.21; range 21-34) and 13 older (mean age = 60; SD = 6.27; range 51-69) pilots, recruited from local flying clubs, with current FAA medical certificates.We examined the effects of alcohol versus placebo in the two age groups and at two times, ie, acute intoxication (target BAC 0.10%) and 8-hour post-drink. Subjects flew a Frasca 141 simulator in a flight task that they had previously learned but not practiced for several months. After completing a baseline flight, pilots were tested during either an alcohol or a placebo condition at the two timepoints. The main outcome measure was a composite measure of flight performance based upon the mean of eight component standardized scores from different aspects of the flight task.We found detrimental effects of alcohol on the main outcome measure both at the acute and 8-hour post-drink testing. There was also no significant difference between the older and younger pilots' performance of the flight task or in susceptibility to alcohol either while intoxicated or during hangover.This study replicates the findings of earlier studies that an 8-hour waiting period from "Bottle-to-Throttle" is insufficient but finds little difference according to age in recollection of a previously learned task or in susceptibility to either acute or hangover effects of alcohol.

    View details for Web of Science ID A1994NQ25100001

    View details for PubMedID 8201140

  • HOW FAR VS HOW FAST IN ALZHEIMERS-DISEASE - THE QUESTION REVISITED ARCHIVES OF NEUROLOGY Kraemer, H. C., Tinklenberg, J., Yesavage, J. A. 1994; 51 (3): 275-279

    Abstract

    To expand on a recent study of 42 patients with probable Alzheimer's Disease that found that the only significant predictors of certain clinical end points were the degree of severity features at entry ("how far").A case series study of a cohort of 81 patients with Alzheimer's disease that used survival analysis methods similar those of the previous study but included a new technique for calculating rate of progression ("how fast") as well as entry characteristics ("how far").A university medical center and its affiliated Veterans Affairs Medical Center.All patients with probable and definite Alzheimer's disease studied at the Aging Clinical Research Center at Stanford University, Palo Alto, Calif, in the years 1981 and 1992 who met the following criteria: a mild to moderate level of severity of the disease (Mini-Mental State Examination score of 15 or above) at entry into the study and a minimum of three test points spaced approximately 6 months apart (to allow estimation of rate of progression). A total of 81 such patients were identified. These patients had been followed up for a mean of 4.53 +/- 2.3 years, with a range of 1.0 to 14.5 years.The outcome measure was the average rate of decline on the Mini-Mental State Examination.The results of our study replicated a previous finding that the degree of severity is a strong predictor of time course, but in addition we found that the rate of progression also appears to be a strong predictor of clinical course.There appears to be substantial heterogeneity in the rate of progression in patients with Alzheimer's disease, and, like initial degree of severity, rate of progression appears to be a strong predictor of clinical course.

    View details for Web of Science ID A1994NA08900013

    View details for PubMedID 8129639

  • Spontaneous mnemonic strategies used by older and younger adults to remember proper names. Memory Brooks, J. O., Friedman, L., Gibson, J. M., Yesavage, J. A. 1993; 1 (4): 393-407

    Abstract

    Little attention has been focused on the spontaneous mnemonic strategies that people use to remember proper names. In the experiment reported here, groups of younger (< 25 years old) and older subjects (> or = 55 years old) were shown a series of 12 name-face pairs and instructed to remember them. In a subsequent test, they were shown the same faces and asked to recall the corresponding names. After the recall task, subjects completed a questionnaire about the mnemonic strategies they used. Our analyses revealed not only that the younger subjects recalled more names than did the older subjects, but also that older and younger subjects reported using certain strategies more frequently than other strategies. Moreover, regression analyses indicated that use of certain mnemonic strategies accounted for a significant proportion of recall performance beyond that accounted for by age alone. Older-old subjects (> or = 70 years old) recalled fewer names than did younger-old subjects (> or = 55 and < 70 years old), but they did not differ in the extent to which they used specific mnemonic strategies. Our results suggest that the use of spontaneous mnemonic strategies may play a role in the difference in proper name recall between younger and older adults.

    View details for PubMedID 7584279

  • Cognitive decline in Alzheimer's disease: elaborating on the nature of the longitudinal factor structure of the Mini-Mental State Examination. International psychogeriatrics Brooks, J. O., Yesavage, J. A., Taylor, J., Friedman, L., Tanke, E. D., LUBY, V., Tinklenberg, J. 1993; 5 (2): 135-146

    Abstract

    The purpose of this paper was to use the Wechsler Adult Intelligence Scale (WAIS) to further define the nature of the underlying factors of the Mini-Mental State Examination (MMSE) as proposed by Tinklenberg et al. (1990). The MMSE was administered to 51 patients once every 6 months for at least one year; the WAIS was administered only at the beginning of the study. Stepwise regression analyses yielded these results: for the Following Commands factor, the best correlate was the Comprehension subtest; for the Language Repetition factor, the best correlate was the Picture Arrangement subtest; and for the Language Expression factor, the best correlates were the Digit Symbol and Object Assembly subtests. These relations help clarify the correlates of decline of AD patients on the MMSE.

    View details for PubMedID 8292767

  • THE TIME-COURSE OF ALCOHOL IMPAIRMENT OF GENERAL-AVIATION PILOT PERFORMANCE IN A FRASCA 141 SIMULATOR AVIATION SPACE AND ENVIRONMENTAL MEDICINE Morrow, D., Yesavage, J., LEIRER, V., DOLHERT, N., Taylor, J., Tinklenberg, J. 1993; 64 (8): 697-705

    Abstract

    This study examined the time-course of alcohol impairment of general aviation pilot simulator performance. We tested 14 young (mean age 25.8 years) and 14 older (mean age 37.9 years) pilots in a Frasca 141 simulator during alcohol and placebo conditions. In the alcohol condition, pilots drank alcohol and were tested after reaching 0.10% BAL, and then 2, 4, 8, 24, and 48 h after they had stopped drinking. They were tested at the same times in the placebo condition. Alcohol impaired overall performance. Alcohol impairment also depended on the order in which subjects participated in the alcohol and placebo sessions, with larger decrements for the alcohol-placebo order than for the opposite order. To examine the influence of alcohol independent of session order effects, we compared performance in the first alcohol session with performance in the first placebo session. This analysis showed that alcohol significantly reduced mean performance in the alcohol condition at 0.10% BAL and at 2 h. In addition, alcohol increased variability in performance in the alcohol session from 0.10% BAL to 8 h, suggesting that some subjects were more susceptible to alcohol than others. Older pilots tended to perform some radio communication tasks less accurately than younger pilots.

    View details for Web of Science ID A1993LP56600003

    View details for PubMedID 8368982

  • DEPRESSION AS A CONFOUNDING VARIABLE IN THE ESTIMATION OF HABITUAL SLEEP TIME JOURNAL OF CLINICAL PSYCHOLOGY Bliwise, D. L., Friedman, L., Yesavage, J. A. 1993; 49 (4): 471-477

    Abstract

    Self-reported habitual sleep time is an important variable because short and long sleep times are associated with mortality. Speculation with regard to these results usually focuses on physical health, rather than psychological factors. We investigated the role of anxiety and depression in reports of habitual sleep times by examining the relative and absolute discrepancy between individuals' initial estimates of their sleep times and sleep diaries made over a 2-week period. Results indicated that depressed mood was associated not only with a tendency initially to underestimate length of sleep (relative discrepancy), but also to exaggerate reported sleep time regardless of direction (absolute discrepancy). These results imply that studies that examine relationships between reported sleep times and mortality should take mental health factors into account.

    View details for Web of Science ID A1993LT78200002

    View details for PubMedID 8408673

  • THE METHODOLOGY OF STUDYING DECLINE IN ALZHEIMERS-DISEASE JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Brooks, J. O., Kraemer, H. C., Tanke, E. D., Yesavage, J. A. 1993; 41 (6): 623-628

    Abstract

    To present a new model for analyzing longitudinal data. The trilinear model is superior to the commonly used linear model that includes the flawed assumption that decline is uniform throughout the course of disease--an assumption that does not correspond to clinical observations.A longitudinal cohort sample was used to compare the linear and trilinear models. Simulated longitudinal data were generated to assess classification errors with the trilinear model.The subjects were 80 patients with Alzheimer's disease tested in a hospital out-patient clinic.The trilinear model describes Alzheimer's disease as proceeding through three periods: An initial period of stability before detectable decline, a period of decline, and a final period of stability during which there is no further detectable decline. A program for the Apple Macintosh computer is available at no charge to apply the model to data.The analyses indicated that the trilinear model provides a better reflection of decline in Alzheimer's disease than does the linear model. This advantage is present whether the periods of stability reflect a "true" lack of decline or insensitivity of a measurement instrument.The trilinear model provides not only a more accurate estimate of the average rate of change, but also (when possible) estimates of the point at which decline begins and ends. Also, more detailed comparisons of tests could be made by using the trilinear parameters. The trilinear model would benefit researchers engaged in longitudinal research of progressive disorders.

    View details for Web of Science ID A1993LF77600006

    View details for PubMedID 8505459

  • Differential diagnosis between depression and dementia. American journal of medicine Yesavage, J. 1993; 94 (5A): 23S-28S

    Abstract

    The proportion of U.S. citizens > 65 years of age is growing steadily. This aging of the population is expected to bring an increase in the incidence of depression and dementia, two clinical entities common in elderly populations. Although depression and dementia have many similarities, they also have important clinical distinctions. It is important for primary-care physicians to understand these distinctions, since only approximately 20% of patients with depressive symptoms are treated by mental health practitioners.

    View details for PubMedID 8503478

  • DEVELOPMENT OF APHASIA, APRAXIA, AND AGNOSIA AND DECLINE IN ALZHEIMERS-DISEASE AMERICAN JOURNAL OF PSYCHIATRY Yesavage, J. A., Brooks, J. O., Taylor, J., Tinklenberg, J. 1993; 150 (5): 742-747

    Abstract

    The purpose of this study was to compare the stage and the subtype models of disease progression in Alzheimer's disease. The authors address the issue of whether the overall rate of clinical decline is different in Alzheimer's disease patients with and without early development of aphasia, apraxia, or agnosia.The study was a case series study. Two separate cohorts of Alzheimer's disease patients were used, one from an ongoing single center study at Stanford University (N = 57) and the other from a multicenter project across the state of California (N = 70). Patients were assessed every 6 months in the Stanford study and yearly in the state study. All patients were assessed at least three times. The outcome measure was the average rate of decline on the Mini-Mental State examination.The average rates of decline on the Mini-Mental State were computed for each subject. Subjects were then divided among groups according to whether and when they exhibited aphasia, agnosia, or apraxia. The effects of the presence of aphasia, agnosia, or apraxia were assessed by comparing the average rates of decline on the Mini-Mental State.Alzheimer's disease patients who developed aphasia or apraxia declined more rapidly than those patients who did not develop either sign. These results were not attributable to differences in Mini-Mental State scores at entry into the study. The results suggest the presence of subtypes of Alzheimer's disease in which accelerated decline is associated with the early appearance of certain neurological signs.

    View details for Web of Science ID A1993LA32300010

    View details for PubMedID 8480819

  • GREATER ABNORMALITIES OF BRAIN CEREBROSPINAL-FLUID VOLUMES IN YOUNGER THAN IN OLDER PATIENTS WITH ALZHEIMERS-DISEASE ARCHIVES OF NEUROLOGY SULLIVAN, E. V., Shear, P. K., Mathalon, D. H., Lim, K. O., Yesavage, J. A., Tinklenberg, J. R., Pfefferbaum, A. 1993; 50 (4): 359-373

    Abstract

    This study used a semiautomated analysis technique to quantify differences in regional brain cerebrospinal fluid volumes observed with computed tomography between healthy adults and patients with Alzheimer's disease (AD).Cross-sectional, between-subject design, using an age-regression model.Palo Alto (Calif) Department of Veterans Affairs Medical Center.The 117 patients with probable or definite AD were recruited from the Geriatric Psychiatry Research Unit and National Institute of Mental Health Clinical Research Center of the Palo Alto Department of Veterans Affairs Medical Center. The 114 healthy volunteers were recruited from the local community.Cerebrospinal fluid volumes estimated from computed tomographic scans and neuropsychological test scores.The computed tomographic estimates of ventricular and sulcal cerebrospinal fluid volumes increased significantly in all sampled brain regions in normal aging and were vastly larger in AD than in normal aging. Furthermore, younger patients with AD had significantly greater cerebrospinal fluid volume enlargement than did older patients with AD compared with healthy controls of their age. When the AD group was divided on the basis of reported age at symptom onset, patients in the early-onset group (onset before age 65 years) were quantitatively more abnormal than and showed a different pattern of abnormality from the patients in the late-onset group. This onset difference was also evident in neuropsychological test performance.This cross-sectional study revealed a number of converging findings that suggested greater abnormality in the early-onset than in the late-onset group of patients with AD. The possibility remains, however, that the two onset groups represent different stages along a continuum of pathologic changes.

    View details for Web of Science ID A1993KV70200007

    View details for PubMedID 8460957

  • A study of the problems older adults encounter when using a mnemonic technique. International psychogeriatrics Brooks, J. O., Friedman, L., Yesavage, J. A. 1993; 5 (1): 57-65

    Abstract

    This study explored problems older adults experience when using a mnemonic technique known as the method of loci. Older subjects received six hours of imagery, judgment, and relaxation pretraining followed by mnemonic training for either four or six hours (Regular or Extended training, respectively). At the end of training, subjects were given a list of the constituent steps of the method of loci and asked to indicate which, if any, were problematic. The factor structure of the relations among the problems varied according to the length of the training subjects received. Specifically, the factor structure of the difficulties reported by the Regular training group reflected problems with using the steps involved in the application of the method of loci, whereas for the Extended training group the factor structure reflected problems with abilities called upon in using the technique. Thus, even with Extended training, subjects may need additional pretraining to develop specific abilities necessary for the successful application of the mnemonic.

    View details for PubMedID 8499575

  • USE OF THE WRIST ACTIGRAPH TO STUDY INSOMNIA IN OLDER ADULTS SLEEP Brooks, J. O., Friedman, L., Bliwise, D. L., Yesavage, J. A. 1993; 16 (2): 151-155

    Abstract

    Measures derived from the wrist actigraph have been found to correlate highly with EEG measures of normal sleep. Although the actigraph has been used to study normal sleep, few studies have used the actigraph as a measure of sleep of elderly insomniacs. The present study, which used elderly insomniacs, sought to investigate the sensitivity of the actigraph to detect the effects of an insomnia treatment. The actigraph was sufficiently sensitive to detect the effect of the sleep restriction therapy used on several sleep measures. Subsidiary analyses suggested that the sleep log, although not an accurate measure of sleep, may be useful as a measure of elderly insomniacs' subjective perception of sleep. Because the actigraph can be used more easily and less expensively than the polysomnogram, the actigraph appears to be a promising measure for assessing the efficacy of treatment interventions in elderly insomniacs.

    View details for Web of Science ID A1993KN60100009

    View details for PubMedID 8446835

  • INFLUENCE OF AGING AND PRACTICE ON PILOTING TASKS EXPERIMENTAL AGING RESEARCH Morrow, D., Yesavage, J., LEIRER, V., Tinklenberg, J. 1993; 19 (1): 53-70

    Abstract

    We examined how pilot age influences radio communication and routine flying tasks during simulated flight, and if practice reduces age differences in these tasks. The communication task involved reading back and executing messages with four commands (heading, altitude, communication frequency, transponder code). Routine flying tasks included takeoff, visual approach, and landing. Fifteen older (X = 38.4 years) and 16 younger (X = 26.1 years) private-license pilots flew 12 flights involving these tasks. Age differences were found in the communication task; older pilots read back and executed controller messages less accurately. However, age differences were not significant for any of the routine flying tasks except the approach. Age differences in communication performance were not reduced by practice, with older and young pilots improving at roughly the same rate across flights. These results are consistent with previous research showing age-related declines in working memory capacity. Capacity declines would produce greater age differences on communication than on routine flying tasks because the communication tasks imposed a greater load on working memory.

    View details for Web of Science ID A1993KN48000005

    View details for PubMedID 8444267

  • TIMING OF SLEEP AND WAKEFULNESS IN ALZHEIMERS-DISEASE PATIENTS RESIDING AT HOME BIOLOGICAL PSYCHIATRY Bliwise, D. L., Tinklenberg, J. R., Yesavage, J. A. 1992; 31 (11): 1163-1165

    View details for Web of Science ID A1992JK71800011

    View details for PubMedID 1525280

  • DEPRESSION IN THE ELDERLY - HOW TO RECOGNIZE MASKED SYMPTOMS AND CHOOSE APPROPRIATE THERAPY POSTGRADUATE MEDICINE Yesavage, J. A. 1992; 91 (1): 255-?

    Abstract

    Depression in the elderly is one of the most serious undiagnosed health problems in the United States. All physicians who care for elderly patients need to become aware of the signs of masked depression and treat it vigorously. Dr Yesavage explains how to differentiate depression from dementia, describes useful diagnostic screening tests, and offers recommendations for pharmacologic treatment of geriatric depression.

    View details for Web of Science ID A1992HA24700024

    View details for PubMedID 1728777

  • NUTRITIONAL INTAKE IN PATIENTS WITH SENILE DEMENTIA OF THE ALZHEIMER TYPE ALZHEIMER DISEASE & ASSOCIATED DISORDERS Winograd, C. H., Jacobson, D. H., Butterfield, G. E., CRAGEN, E., EDLER, L. A., Taylor, B. S., Yesavage, J. A. 1991; 5 (3): 173-180

    Abstract

    The dietary intake of 29 healthy controls was compared with that of 35 community-dwelling patients with probable or definite senile dementia of the Alzheimer type (SDAT), based on NINCDS-ADRDA criteria. The control subject or the caregiver of the SDAT patient completed a 3-day estimated-dietary-intake record. Foods offered to patients were chosen, for the most part, by caregivers, but SDAT patients were allowed to eat ad libitum from those choices, and food consumed was recorded. Dietary intake was evaluated against the 1989 Recommended Dietary Allowances (RDA). Dietary intakes did not differ significantly between control and SDAT patients for any of the 32 nutrients analyzed. The controls and SDAT patients met the RDA guidelines for intake of total energy, protein, and micronutrients, with the exception of female SDAT patients, who did not consume a minimum of two thirds of the RDA for vitamin D. All biochemical indices of nutritional status were within normal limits for the SDAT patients. In addition, cognitive function did not correlate with intake of any nutrient studied. We conclude that moderately impaired, community-dwelling patients with SDAT do not differ from healthy controls in nutritional status or nutrient intake. Neither general nor nutrient-specific malnutrition was present in this population. Based on this cross-sectional study, malnutrition does not appear to be a major contributor to the pathogenesis of Alzheimer disease. However, this investigation examined only a single point in time, when patients were being fed by caregivers, so that the role of malnutrition at the beginning of the disease was not addressed.

    View details for Web of Science ID A1991GU43100003

    View details for PubMedID 1772637

  • BLOOD-GLUCOSE AND INSULIN-RESPONSE IN PATIENTS WITH SENILE DEMENTIA OF THE ALZHEIMERS TYPE BIOLOGICAL PSYCHIATRY Winograd, C. H., Jacobson, D. H., Minkoff, J. R., Peabody, C. A., Taylor, B. S., WIDROW, L., Yesavage, J. A. 1991; 30 (5): 507-511

    View details for Web of Science ID A1991GE87200011

    View details for PubMedID 1932397

  • MARIJUANA CARRY-OVER EFFECTS ON AIRCRAFT PILOT PERFORMANCE AVIATION SPACE AND ENVIRONMENTAL MEDICINE Leirer, V. O., Yesavage, J. A., Morrow, D. G. 1991; 62 (3): 221-227

    Abstract

    This study finds evidence for 24-h carry-over effects of a moderate social dose of marijuana on a piloting task. In separate sessions, nine currently active pilots smoked one cigarette containing 20 mg of delta 9 THC and one Placebo cigarette. Using an aircraft simulator, pilots flew just before smoking, and 0.25, 4, 8, 24, and 48 h after smoking. Marijuana impaired performance at 0.25, 4, 8, and 24 h after smoking. While seven of the nine pilots showed some degree of impairment at 24 h after smoking, only one reported any awareness of the drug's effects. The results support our preliminary study and suggest that very complex human/machine performance can be impaired as long as 24 h after smoking a moderate social dose of marijuana, and that the user may be unaware of the drug's influence.

    View details for Web of Science ID A1991EZ17100005

    View details for PubMedID 1849400

  • ALCOHOL, AGE, AND PILOTING - JUDGMENT, MOOD, AND ACTUAL PERFORMANCE INTERNATIONAL JOURNAL OF THE ADDICTIONS Morrow, D., LEIRER, V., Yesavage, J., Tinklenberg, J. 1991; 26 (6): 669-683

    Abstract

    We have previously described acute and carry-over effects of alcohol on young and older pilots' performance. In the present paper we report the effects of alcohol and age on self-assessment of performance and mood in the same study. Young and older pilots flew in a simulator during an alcohol and placebo condition. In the alcohol condition, they flew after reaching .04 g/dL (.04%) BAL, after .10% BAL, and then 2, 4, 8, 24, and 48 h after .10% BAL (they flew at the same times in the placebo condition). They rated confidence in ability to fly, mood, alertness, and intoxication before each flight, and perceived workload and performance after each flight. As reported in Morrow et al., alcohol had both acute and carry-over effects for 8 h on actual flight performance, with greater acute impairment for older pilots. The present study reports that these older pilots tended to be more aware than the young pilots of acute and carry-over alcohol impairment out to 4 h. By 8 h, however, all pilots were unaware of impairment. Alcohol also had a biphasic effect on mood, which increased on the ascending limb and decreased on the descending limb of the BAL curve.

    View details for Web of Science ID A1991GF43400004

    View details for PubMedID 1757171

  • A PRELIMINARY-STUDY COMPARING SLEEP RESTRICTION AND RELAXATION TREATMENTS FOR INSOMNIA IN OLDER ADULTS JOURNALS OF GERONTOLOGY Friedman, L., Bliwise, D. L., Yesavage, J. A., SALOM, S. R. 1991; 46 (1): P1-P8

    Abstract

    This study compared Sleep Restriction Therapy (SRT) and Relaxation Therapy (RLT) as treatments for insomnia in a sample of community-residing elderly (mean age, 69.7 years). SRT subjects (n = 10) and RLT subjects (n = 12) reported information about their sleep twice daily to a telephone recording machine for 2 weeks of baseline, 4 weeks of treatment, and 2 weeks at 3-month follow-up. Results showed sleep latency and waking after sleep onset were significantly reduced for both treatment groups under active treatment. Predictable reductions in time in bed and improved sleep efficiency reported during active treatment by SRT subjects were still apparent at 3-month follow-up; no corresponding changes were found for RLT. In both groups, increased total sleep time was reported at follow-up; the improvement for SRT subjects was approximately twice that seen in RLT. These findings, at this early stage in the development of behavioral treatments for insomnia in older adults, encourage further study.

    View details for Web of Science ID A1991FJ10900006

    View details for PubMedID 1986039

  • Cognitive decline in patients with Alzheimer disease: differences in patients with and without extrapyramidal signs. Alzheimer disease & associated disorders MILLER, T. P., Tinklenberg, J. R., Brooks, J. O., Yesavage, J. A. 1991; 5 (4): 251-256

    Abstract

    We investigated the relationship between extrapyramidal signs (EPSs) in patients diagnosed with Alzheimer disease (AD) and the average rate of decline in different areas of cognition. The presence of tremors, cogwheel rigidity, or bradykinesia were scored as EPS using the California State Department of Health Services AD Diagnostic and Treatment Center Form. Measures of decline were computed by determining patients' average rates of decline on the Mini-Mental State Examination (MMSE). Of the 81 patients, 24 were determined to have EPS not related to medications. Overall, patients with EPS deteriorated 67% faster on MMSE (4.5 points per year) than did patients with no evidence of EPS (2.7 points per year). Our findings indicate that the clinical presence of EPS is a poor overall prognostic sign in patients with a clinical diagnosis of AD.

    View details for PubMedID 1781967

  • THE INFLUENCE OF ALCOHOL AND AGING ON RADIO-COMMUNICATION DURING FLIGHT AVIATION SPACE AND ENVIRONMENTAL MEDICINE Morrow, D., LEIRER, V., Yesavage, J. 1990; 61 (1): 12-20

    Abstract

    This study finds that alcohol and pilot age impair radio communication during simulated flight. Young (mean age 25 years) and older (mean age 42 years) pilots flew in a light aircraft simulator during alcohol and placebo conditions. In the alcohol condition, pilots drank alcohol and flew after reaching 0.04% BAC, after reaching 0.10% BAC, and then 2, 4, 8, 24, and 48 h after they stopped drinking at 0.10% BAC. They flew at the same times in the placebo condition. Alcohol and age impaired communication-based and overall flying performance during and immediately after drinking. Most important, alcohol and age cumulatively impaired performance, since older pilots were more impaired by alcohol. Notably, performance was as impaired 2 h after reaching 0.10% BAC as it was at 0.10% BAC. Moreover, overall performance was impaired for 8 h after reaching 0.10% BAC.

    View details for Web of Science ID A1990CF02700003

    View details for PubMedID 2302121

  • MARIJUANA, AGING, AND TASK-DIFFICULTY EFFECTS ON PILOT PERFORMANCE AVIATION SPACE AND ENVIRONMENTAL MEDICINE LEIRER, O., Yesavage, J. A., Morrow, D. G. 1989; 60 (12): 1145-1152

    Abstract

    This study provides evidence that diverse factors can cumulatively contribute to human/machine performance decrements. In separate sessions, young and old pilots smoked one of three cigarettes containing either 0 mg, 10 mg, or 20 mg of the active ingredient, delta 9 THC. They flew a calm and a turbulent flight in a light aircraft simulator at 1, 4, 8, 24, and 48 hour (h) delay after smoking. Effects were found at 1 and 4 h after smoking in the turbulent flight conditions when 20 mg cigarettes were smoked. Drug dose level, age, weather conditions (i.e., task difficulty), and delay period all affected pilot performance. Most important, these variables produced cumulative performance decrements.

    View details for Web of Science ID A1989CC44500001

    View details for PubMedID 2604668

  • SLEEP-APNEA IN ALZHEIMERS-DISEASE NEUROBIOLOGY OF AGING Bliwise, D. L., Yesavage, J. A., Tinklenberg, J. R., Dement, W. C. 1989; 10 (4): 343-346

    Abstract

    Mental deterioration accompanying sleep apnea has been noted frequently. Because sleep apnea increases with age, such deficits raise the possibility that dementia in the elderly could be related to sleep apnea. In this study we investigated this possibility cross-sectionally by comparing respiration during sleep in 28 patients with Alzheimer's disease (AD) and 25 nondemented controls. We hypothesized that higher levels of sleep apnea would be present in AD patients. Our results indicated no significant differences between AD patients and controls but those few AD patients who desaturated during sleep experienced morning confusion. The findings imply that AD and sleep apnea are two separate conditions which may still interact in the aged.

    View details for Web of Science ID A1989AK79000008

    View details for PubMedID 2812195

  • REM LATENCY IN ALZHEIMERS-DISEASE BIOLOGICAL PSYCHIATRY Bliwise, D. L., Tinklenberg, J., Yesavage, J. A., Davies, H., PURSLEY, A. M., PETTA, D. E., WIDROW, L., Guilleminault, C., Zarcone, V. P., Dement, W. C. 1989; 25 (3): 320-328

    Abstract

    Latency to the first episode of rapid eye movement sleep (REML) has been proposed as a potential biomarker for Alzheimer's disease (AD). In this study, we compared REML values from 28 AD patients and 28 age- and sex-matched controls. We employed multiple definitions of REML and multiple cutoffs to classify patients and controls. Results indicated that the best REML definition and optimal cutoff criterion resulted in only 65% correct classifications. We discuss the longer REML in AD patients relative to controls in terms of both overall sleep disturbance and selective deterioration of the REM-cholinergic system. As REML may be relatively short in other forms of psychopathology (e.g., affective disorders), REML may still hold promise in the differential diagnosis of dementia and pseudodementia.

    View details for Web of Science ID A1989R741100008

    View details for PubMedID 2914155

  • TECHNIQUES FOR COGNITIVE TRAINING OF MEMORY IN AGE-ASSOCIATED MEMORY IMPAIRMENT ARCHIVES OF GERONTOLOGY AND GERIATRICS Yesavage, J. A. 1989: 185-190

    View details for Web of Science ID A1989U568100015

    View details for PubMedID 2757731

  • Nonpharmacologic treatment of age-associated memory impairment. Comprehensive therapy Yesavage, J. A., Sheikh, J. I. 1988; 14 (6): 44-46

    View details for PubMedID 3046835

  • VALIDATION OF THE GERIATRIC PSYCHIATRY KNOWLEDGE TEST HOSPITAL AND COMMUNITY PSYCHIATRY Sheikh, J. I., Yesavage, J. A., GULEVICH, G. 1988; 39 (4): 369-?

    View details for Web of Science ID A1988M776800003

    View details for PubMedID 3371903

  • TARDIVE-DYSKINESIA AND STEADY-STATE SERUM LEVELS OF THIOTHIXENE ARCHIVES OF GENERAL PSYCHIATRY Yesavage, J. A., Tanke, E. D., Sheikh, J. I. 1987; 44 (10): 913-915

    Abstract

    The purpose of this investigation was to determine the relationship between serum levels of the neuroleptic agent thiothixene and tardive dyskinesia in schizophrenics of a wide age range. Forty-one male schizophrenic subjects, 21 with tardive dyskinesia and 20 without, were given a fixed dosage of thiothixene hydrochloride (10 mg orally four times daily) after a drug-free period of one week. Higher steady-state serum levels of thiothixene (obtained after five days of a fixed-dosage schedule) were associated with greater degrees of tardive dyskinesia. This relationship was independent of the relationship between tardive dyskinesia and age.

    View details for Web of Science ID A1987K304500011

    View details for PubMedID 2889439

  • IMAGERY MNEMONIC TRAINING IN A PATIENT WITH PRIMARY DEGENERATIVE DEMENTIA PSYCHOLOGY AND AGING Hill, R. D., Evankovich, K. D., Sheikh, J. I., Yesavage, J. A. 1987; 2 (2): 204-205

    Abstract

    A visual-imagery mnemonic was used as a memory training aid for a 66-year-old patient with primary degenerative dementia. Length of retention time was used as the primary outcome measure. The application of the mnemonic procedure extended the length of retention time for name-face recall from baseline. Performance gains were sustained at one month.

    View details for Web of Science ID A1987H556800013

    View details for PubMedID 3268209

  • NONPHARMACOLOGIC TREATMENTS FOR MEMORY LOSSES WITH NORMAL AGING AMERICAN JOURNAL OF PSYCHIATRY Yesavage, J. A. 1985; 142 (5): 600-605

    Abstract

    In a critical review of studies of training programs for elderly individuals with cognitive deficits, the author found that decrements of cognitive function with aging are not small. In 70-year-old normal individuals, losses are on the order of 20%-40%, depending on the process tested and the testing method. Although long-term effects are poorly documented, training programs for normal elderly individuals have been shown to improve selected cognitive processes, including memory, to about the same degree that some of these processes decline with aging.

    View details for Web of Science ID A1985AGG2500012

    View details for PubMedID 3885762

  • Development and validation of a geriatric depression screening scale: a preliminary report. Journal of psychiatric research Yesavage, J. A., Brink, T. L., Rose, T. L., LUM, O., Huang, V., ADEY, M., Leirer, V. O. 1982; 17 (1): 37-49

    Abstract

    A new Geriatric Depression Scale (GDS) designed specifically for rating depression in the elderly was tested for reliability and validity and compared with the Hamilton Rating Scale for Depression (HRS-D) and the Zung Self-Rating Depression Scale (SDS). In constructing the GDS a 100-item questionnaire was administered to normal and severely depressed subjects. The 30 questions most highly correlated with the total scores were then selected and readministered to new groups of elderly subjects. These subjects were classified as normal, mildly depressed or severely depressed on the basis of Research Diagnostic Criteria (RDC) for depression. The GDS, HRS-D and SDS were all found to be internally consistent measures, and each of the scales was correlated with the subject's number of RDC symptoms. However, the GDS and the HRS-D were significantly better correlated with RDC symptoms than was the SDS. The authors suggest that the GDS represents a reliable and valid self-rating depression screening scale for elderly populations.

    View details for PubMedID 7183759

Conference Proceedings


  • Structural brain correlates of verbal and nonverbal fluency measures in Alzheimer's disease Fama, R., Sullivan, E. V., Shear, P. K., Cahn-Weiner, D. A., Marsh, L., Lim, K. O., Yesavage, J. A., Tinklenberg, J. R., Pfefferbaum, A. AMER PSYCHOLOGICAL ASSOC. 2000: 29-40

    Abstract

    This study examined the relationships between regional brain volumes and semantic, phonological, and nonverbal fluency in 32 participants with Alzheimer's disease (AD). Object but not animal semantic fluency correlated with frontal and temporal gray matter volumes. Phonological fluency was not significantly associated with any brain volume examined. Nonverbal fluency was selectively associated with bilateral frontal gray matter volumes. Hippocampal volumes, although markedly reduced in these patients, were not related to any of the fluency measures. Results lend evidence to the importance of the frontal lobes in the directed generation of nonverbal and verbal exemplars by AD patients. Furthermore, both left- and right-hemisphere regions contribute to the generation of verbal and nonverbal exemplars.

    View details for Web of Science ID 000085020000003

    View details for PubMedID 10674796

  • Brain structural and cognitive correlates of clock drawing performance in Alzheimer's disease Cahn-Weiner, D. A., SULLIVAN, E. V., Shear, P. K., Fama, R., Lim, K. O., Yesavage, J. A., Tinklenberg, J. R., Pfefferbaum, A. CAMBRIDGE UNIV PRESS. 1999: 502-509

    Abstract

    The Clock Drawing Test (CDT) is widely used in the assessment of dementia and is known to be sensitive to the detection of deficits in neurodegenerative disorders such as Alzheimer's disease (AD). CDT performance is dependent not only on visuospatial and constructional abilities, but also on conceptual and executive functioning; therefore, it is likely to be mediated by multiple brain regions. The purpose of the present study was to identify component cognitive processes and regional cortical volumes that contribute to CDT performance in AD. In 29 patients with probable AD, CDT performance was significantly related to right-, but not left-hemisphere, regional gray matter volume. Specifically, CDT score correlated significantly with the right anterior and posterior superior temporal lobe volumes. CDT scores showed significant relationships with tests of semantic knowledge, executive function, and visuoconstruction, and receptive language. These results suggest that in AD patients, CDT performance is attributable to impairment in multiple cognitive domains but is related specifically to regional volume loss of right temporal cortex.

    View details for Web of Science ID 000083339700003

    View details for PubMedID 10561930

  • Selective cortical and hippocampal volume correlates of Mattis Dementia Rating Scale in Alzheimer disease Fama, R., SULLIVAN, E. V., Shear, P. K., Marsh, L., Yesavage, J. A., Tinklenberg, J. R., Lim, K. O., Pfefferbaum, A. AMER MEDICAL ASSOC. 1997: 719-728

    Abstract

    To examine whether each of the 5 Mattis Dementia Rating Scale (DRS) scores related to magnetic resonance imaging-derived volumes of specific cortical or limbic brain regions in patients with Alzheimer disease (AD).Relations between DRS measures and regional brain volume measures were tested with bivariate and multivariate regression analyses.The Aging Clinical Research Center of the Stanford (Calif) University Department of Psychiatry and Behavioral Science and the Geriatric Psychiatry Rehabilitation Unit of the Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif.Fifty patients with possible or probable AD. Magnetic resonance imaging data from 136 healthy control participants, age 20 to 84 years, were used to correct brain volumes for normal variation arising from intracranial volume and age.The DRS scores and volumes of regional cortical gray matter and of the hippocampus.Memory scores of the patients with AD were selectively related to hippocampal volumes. Attention and construction scores were related to several anterior brain volume measures, with attention showing a significantly greater association to right than left hemisphere measures. Initiation/perseveration scores were not significantly correlated with any measure of regional gray matter volume, but performance was related to prefrontal sulcal widening, with a greater association with the left than right sulcal volume.Certain DRS subtests are predictably correlated with selective regional brain volumes in AD. The specific relation between memory and hippocampal volumes and the nonsignificant relations between memory and regional cortical volumes suggest a dissociation between cortical and hippocampal contributions to explicit memory performance.

    View details for Web of Science ID A1997XE00100008

    View details for PubMedID 9193207

  • IDENTIFICATION OF FAST AND SLOW DECLINERS IN ALZHEIMER-DISEASE - A DIFFERENT APPROACH Brooks, J. O., Yesavage, J. A. LIPPINCOTT WILLIAMS & WILKINS. 1995: S19-S25

    Abstract

    As the body of knowledge about Alzheimer disease (AD) expands, more evidence is appearing to suggest the existence of different subtypes. The delineation of subtypes is important for a variety of reasons, and there are probably several ways to identify subtypes. One crude but functionally promising distinction is between patients with early onset of AD and those with late onset. In theory, such a distinction appears to be a simple one, but critical methodologic issues are involved in this dichotomy, because a key aspect is estimating the rate of progression of the disease in different subtypes. This article discusses potential problems with various measures of deterioration and illustrates how the application of a novel technique--the trilinear model--can address many of these problems and provide additional valuable information. The trilinear model is especially well suited for use in pharmacologic studies because of the additional insight that it can provide.

    View details for Web of Science ID A1995RW67600005

    View details for PubMedID 7546595

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