Performance variability during a multitrial list-learning task as a predictor of future cognitive decline in healthy elders
JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY
2014; 36 (3): 236-243
Recognition of famous names predicts cognitive decline in healthy elders.
2013; 27 (3): 333-342
In clinical settings, neuropsychological test performance is traditionally evaluated with total summary scores (TSS). However, recent studies demonstrated that indices of intraindividual variability (IIV) yielded unique information complementing TSS. This 18-month longitudinal study sought to determine whether IIV indices derived from a multitrial list-learning test (the Rey Auditory Verbal Learning Test) provided incremental utility in predicting cognitive decline in older adults compared to TSS.Ninety-nine cognitively intact older adults (aged 65 to 89 years) underwent neuropsychological testing (including the Rey Auditory Verbal Learning Test) at baseline and 18-month follow-up. Participants were classified as cognitively stable (n = 65) or declining (n = 34) based on changes in their neuropsychological test performance. Logistic regression modeling tested the ability of baseline TSS indices (sum of Trials 1-5, immediate recall, and delayed recall) and IIV indices (lost access and gained access) to discriminate between stable and declining individuals.Higher values of both lost access and gained access at baseline were associated with an increased risk for decline at 18-month follow-up. Further, the IIV indices provided predictive utility above and beyond the TSS indices.These results highlight the value of analyzing IIV in addition to TSS during neuropsychological evaluation in older adults. High levels of IIV may reflect impairment in anterograde memory systems and/or executive dysfunction that may serve as a prognostic indicator of cognitive decline.
View details for DOI 10.1080/13803395.2013.877875
View details for Web of Science ID 000334032600002
View details for PubMedID 24552205
Semantic Memory Functional MRI and Cognitive Function after Exercise Intervention in Mild Cognitive Impairment
JOURNAL OF ALZHEIMERS DISEASE
2013; 37 (1): 197-215
The ability to recognize familiar people is impaired in both Mild Cognitive Impairment (MCI) and Alzheimer's Dementia (AD). In addition, both groups often demonstrate a time-limited temporal gradient (TG) in which well known people from decades earlier are better recalled than those learned recently. In this study, we examined the TG in cognitively intact elders for remote famous names (1950-1965) compared to more recent famous names (1995-2005). We hypothesized that the TG pattern on a famous name recognition task (FNRT) would predict future cognitive decline, and also show a significant correlation with hippocampal volume.Seventy-eight healthy elders (ages 65-90) with age-appropriate cognitive functioning at baseline were administered a FNRT. Follow-up testing 18 months later produced two groups: Declining (≥ 1 SD reduction on at least one of three measures) and Stable (< 1 SD).The Declining group (N = 27) recognized fewer recent famous names than the Stable group (N = 51), although recognition for remote names was comparable. Baseline MRI volumes for both the left and right hippocampi were significantly smaller in the Declining group than the Stable group. Smaller baseline hippocampal volume was also significantly correlated with poorer performance for recent, but not remote famous names. Logistic regression analyses indicated that baseline TG performance was a significant predictor of group status (Declining vs. Stable) independent of chronological age and APOE ε4 inheritance.The TG for famous name recognition may serve as an early preclinical cognitive marker of cognitive decline in healthy older individuals.
View details for DOI 10.1037/a0032226
View details for PubMedID 23688215
Comparison of semantic and episodic memory BOLD fMRI activation in predicting cognitive decline in older adults.
Journal of the International Neuropsychological Society
2013; 19 (1): 11-21
Mild cognitive impairment (MCI) is associated with early memory loss, Alzheimer's disease (AD) neuropathology, inefficient or ineffective neural processing, and increased risk for AD. Unfortunately, treatments aimed at improving clinical symptoms or markers of brain function generally have been of limited value. Physical exercise is often recommended for people diagnosed with MCI, primarily because of its widely reported cognitive benefits in healthy older adults. However, it is unknown if exercise actually benefits brain function during memory retrieval in MCI. Here, we examined the effects of exercise training on semantic memory activation during functional magnetic resonance imaging (fMRI). Seventeen MCI participants and 18 cognitively intact controls, similar in sex, age, education, genetic risk, and medication use, volunteered for a 12-week exercise intervention consisting of supervised treadmill walking at a moderate intensity. Both MCI and control participants significantly increased their cardiorespiratory fitness by approximately 10% on a treadmill exercise test. Before and after the exercise intervention, participants completed an fMRI famous name discrimination task and a neuropsychological battery, Performance on Trial 1 of a list-learning task significantly improved in the MCI participants. Eleven brain regions activated during the semantic memory task showed a significant decrease in activation intensity following the intervention that was similar between groups (p-values ranged 0.048 to 0.0001). These findings suggest exercise may improve neural efficiency during semantic memory retrieval in MCI and cognitively intact older adults, and may lead to improvement in cognitive function. Clinical trials are needed to determine if exercise is effective to delay conversion to AD.
View details for DOI 10.3233/JAD-130467
View details for Web of Science ID 000323487300018
View details for PubMedID 23803298
Lifestyle and Genetic Contributions to Cognitive Decline and Hippocampal Structure and Function in Healthy Aging
CURRENT ALZHEIMER RESEARCH
2012; 9 (4): 436-446
Previous studies suggest that task-activated functional magnetic resonance imaging (fMRI) can predict future cognitive decline among healthy older adults. The present fMRI study examined the relative sensitivity of semantic memory (SM) versus episodic memory (EM) activation tasks for predicting cognitive decline. Seventy-eight cognitively intact elders underwent neuropsychological testing at entry and after an 18-month interval, with participants classified as cognitively "Stable" or "Declining" based on ≥ 1.0 SD decline in performance. Baseline fMRI scanning involved SM (famous name discrimination) and EM (name recognition) tasks. SM and EM fMRI activation, along with Apolipoprotein E (APOE) ε4 status, served as predictors of cognitive outcome using a logistic regression analysis. Twenty-seven (34.6%) participants were classified as Declining and 51 (65.4%) as Stable. APOE ε4 status alone significantly predicted cognitive decline (R(2) = .106; C index = .642). Addition of SM activation significantly improved prediction accuracy (R(2) = .285; C index = .787), whereas the addition of EM did not (R(2) = .212; C index = .711). In combination with APOE status, SM task activation predicts future cognitive decline better than EM activation. These results have implications for use of fMRI in prevention clinical trials involving the identification of persons at-risk for age-associated memory loss and Alzheimer's disease.
View details for DOI 10.1017/S1355617712000951
View details for PubMedID 23199565
Does physical activity influence semantic memory activation in amnestic mild cognitive impairment?
2011; 193 (1): 60-62
Engagement in cognitively stimulating activities (CA) and leisure time physical activity (PA) have been associated with maintaining cognitive performance and reducing the likelihood of cognitive decline in older adults. However, neural mechanisms underlying protective effects of these lifestyle behaviors are largely unknown. In the current study, we investigated the effect of self-reported PA and CA on hippocampal volume and semantic processing activation during a fame discrimination task, as measured by functional magnetic resonance imaging (fMRI). We also examined whether possession of the apolipoprotein E (APOE) ε4 allele could moderate the effect of PA or CA on hippocampal structure or function.Seventy-eight healthy, cognitively intact older adults underwent baseline neuropsychological assessment, hippocampal volume measurement via manually-traced structural MRI, and task-activated fMRI.After 18 months, 27 participants declined by one standard deviation or more on follow-up neuropsychological testing. Logistic regression analyses revealed that CA alone or in combination with baseline hippocampal structure or functional activity did not predict the probability of cognitive decline. In contrast, PA interacted with APOE 4 status such that engagement in PA reduced the risk of cognitive decline in APOE 4 carriers only. Furthermore, the benefits of PA appeared to diminish with reduced functional activity or volume in the hippocampus.Our findings suggest that increased leisure time PA is associated with reduced probability of cognitive decline in persons who are at high risk for AD. The beneficial effects of PA in this group may be related to enhancement of the functional and structural integrity of the hippocampus.
View details for Web of Science ID 000304189200005
View details for PubMedID 22272622
Interactive effects of physical activity and APOE-epsilon 4 on BOLD semantic memory activation in healthy elders
2011; 54 (1): 635-644
The effect of physical activity (PA) on functional brain activation for semantic memory in amnestic mild cognitive impairment (aMCI) was examined using event-related functional magnetic resonance imaging during fame discrimination. Significantly greater semantic memory activation occurred in the left caudate of High- versus Low-PA patients, (P=0.03), suggesting PA may enhance memory-related caudate activation in aMCI.
View details for DOI 10.1016/j.pscychresns.2011.04.001
View details for Web of Science ID 000292470500009
View details for PubMedID 21601432
Prediction of Cognitive Decline in Healthy Older Adults using fMRI
JOURNAL OF ALZHEIMERS DISEASE
2010; 21 (3): 871-885
Evidence suggests that physical activity (PA) is associated with the maintenance of cognitive function across the lifespan. In contrast, the apolipoproteinE-ε4 (APOE-ε4) allele, a genetic risk factor for Alzheimer's disease (AD), is associated with impaired cognitive function. The objective of this study was to examine the interactive effects of PA and APOE-ε4 on brain activation during memory processing in older (ages 65-85) cognitively intact adults. A cross-sectional design was used with four groups (n=17 each): (1) Low Risk/Low PA; (2) Low Risk/High PA; (3) High Risk/Low PA; and (4) High Risk/High PA. PA level was based on self-reported frequency and intensity. AD risk was based on presence or absence of an APOE-ε4 allele. Brain activation was measured using event-related functional magnetic resonance imaging (fMRI) while participants performed a famous name discrimination task. Brain activation subserving semantic memory processing occurred in 15 functional regions of interest. High PA and High Risk were associated with significantly greater semantic memory activation (famous>unfamiliar) in 6 and 3 of the 15 regions, respectively. Significant interactions of PA and Risk were evident in 9 of 15 brain regions, with the High PA/High Risk group demonstrating greater semantic memory activation than the remaining three groups. These findings suggest that PA selectively increases memory-related brain activation in cognitively intact but genetically at-risk elders. Longitudinal studies are required to determine whether increased semantic memory processing in physically active at-risk individuals is protective against future cognitive decline.
View details for DOI 10.1016/j.neuroimage.2010.07.070
View details for Web of Science ID 000283825000065
View details for PubMedID 20691792
The Personality Assessment Inventory as a tool for diagnosing psychogenic nonepileptic seizures
2010; 51 (1): 161-164
Few studies have examined the extent to which structural and functional MRI, alone and in combination with genetic biomarkers, can predict future cognitive decline in asymptomatic elders. This prospective study evaluated individual and combined contributions of demographic information, genetic risk, hippocampal volume, and fMRI activation for predicting cognitive decline after an 18-month retest interval. Standardized neuropsychological testing, an fMRI semantic memory task (famous name discrimination), and structural MRI (sMRI) were performed on 78 healthy elders (73% female; mean age = 73 years, range = 65 to 88 years). Positive family history of dementia and presence of one or both apolipoprotein E (APOE) ε4 alleles occurred in 51.3% and 33.3% of the sample, respectively. Hippocampal volumes were traced from sMRI scans. At follow-up, all participants underwent a repeat neuropsychological examination. At 18 months, 27 participants (34.6%) declined by at least 1 SD on one of three neuropsychological measures. Using logistic regression, demographic variables (age, years of education, gender) and family history of dementia did not predict future cognitive decline. Greater fMRI activity, absence of an APOE ε4 allele, and larger hippocampal volume were associated with reduced likelihood of cognitive decline. The most effective combination of predictors involved fMRI brain activity and APOE ε4 status. Brain activity measured from task-activated fMRI, in combination with APOE ε4 status, was successful in identifying cognitively intact individuals at greatest risk for developing cognitive decline over a relatively brief time period. These results have implications for enriching prevention clinical trials designed to slow AD progression.
View details for DOI 10.3233/JAD-2010-091693
View details for Web of Science ID 000281903600017
View details for PubMedID 20634590
Semantic memory activation in amnestic mild cognitive impairment
2009; 132: 2068-2078
Using 184 subjects with valid personality assessment interview (PAI) profiles and video-electroencephalography (VEEG)-confirmed diagnoses of epileptic seizures (ES; n = 109) or psychogenic nonepileptic seizures (PNES; n = 75), we present the diagnostic test performance of the PAI PNES Indicator and other PAI scales when used to differentiate PNES from ES. Subjects with PNES reported significantly higher somatic, conversion, depressed, anxious, and suicidal symptoms. As a diagnostic tool, the PNES Indicator does not add additional accuracy beyond the conversion subscale (SOM-C). The somatization (SOM-S) and physiological depression (DEP-P) subscales perform as well as the SOM-C subscale. The SOM-C scale (cut point > or =70) was 58.7% sensitive and 83.5% specific at diagnosing PNES. Assuming a 30% prevalence of PNES, the SOM-C scale has a positive predictive value (PPV) of 60.4% and negative predictive value (NPV) of 82.5%. Overall, the PAI SOM-C subscale does not appear more accurate than other psychometric tests used to differentiate PNES from ES.
View details for DOI 10.1111/j.1528-1167.2009.02151.x
View details for Web of Science ID 000272996300018
View details for PubMedID 19490032
Medication use profiles in patients with psychogenic nonepileptic seizures
EPILEPSY & BEHAVIOR
2007; 10 (2): 333-335
Cognitively intact older individuals at risk for developing Alzheimer's disease frequently show increased functional magnetic resonance imaging (fMRI) brain activation presumably associated with compensatory recruitment, whereas mild cognitive impairment (MCI) patients tend not to show increased activation presumably due to reduced neural reserve. Previous studies, however, have typically used episodic memory activation tasks, placing MCI participants at a performance disadvantage relative to healthy elders. In this event-related fMRI study, we employed a low effort, high accuracy semantic memory task to determine if increased activation of memory circuits is preserved in amnestic MCI when task performance is controlled. Fifty-seven participants, aged 65-85 years, comprised three groups (n = 19 each): amnestic MCI patients; cognitively intact older participants at risk for developing Alzheimer's disease based on having at least one ApoE epsilon4 allele and a positive family history of Alzheimer's disease (At Risk); and cognitively intact participants without Alzheimer's disease risk factors (Control). fMRI was conducted on a 3T MR scanner while participants performed a famous name discrimination task. Participants also underwent neuropsychological testing outside the scanner; whole brain and hippocampal atrophy were assessed from anatomical MRI scans. The three groups did not differ on demographic variables or on fame discrimination performance (>87% correct for all groups). As expected, the amnestic MCI participants demonstrated reduced episodic memory performance. Spatial extent of activation (Fame--Unfamiliar subtraction) differentiated the three groups (Control = 0 ml, At Risk = 9.7 ml, MCI = 34.7 ml). The MCI and At Risk groups showed significantly greater per cent signal change than Control participants in 8 of 14 functionally defined regions, including the medial temporal lobe, temporoparietal junction, and posterior cingulate/precuneus. MCI participants also showed greater activation than Controls in two frontal regions. At Risk, but not MCI, participants showed increased activity in the left hippocampal complex; MCI participants, however, evidenced increased activity in this region when hippocampal atrophy was controlled. When performance is equated, MCI patients demonstrate functional compensation in brain regions subserving semantic memory systems that generally equals or exceeds that observed in cognitively intact individuals at risk for Alzheimer's disease. This hyperactivation profile in MCI is even observed in the left hippocampal complex, but only when the extent of hippocampal atrophy is taken into consideration.
View details for DOI 10.1093/brain/awp157
View details for Web of Science ID 000268330500008
View details for PubMedID 19515831
Patients with psychogenic nonepileptic seizures (PNES) and those with epilepsy may have very different medication use profiles. In this study, the authors set out to document and statistically compare medication use by these two populations. They found significant differences in the duration of antiepileptic medication use (shorter in those with psychogenic nonepileptic seizures, or PNES) and number of medications used (more in persons with PNES) and a tendency by patients with PNES to use narcotics and benzodiazepines. These results are discussed in the light of the pertinent literature.
View details for DOI 10.1016/j.yebeh.2006.11.014
View details for Web of Science ID 000245681100019
View details for PubMedID 17215169