Fasting plasma insulin and the default mode network in women at risk for Alzheimer's disease
NEUROBIOLOGY OF AGING
2013; 34 (3): 641-649
Insulin resistance and hippocampal volume in women at risk for Alzheimer's disease
NEUROBIOLOGY OF AGING
2011; 32 (11): 1942-1948
Brain imaging studies in Alzheimer's disease research have demonstrated structural and functional perturbations in the hippocampus and default mode network (DMN). Additional evidence suggests risk for pathological brain aging in association with insulin resistance (IR). This study piloted investigation of associations of IR with DMN-hippocampal functional connectivity among postmenopausal women at risk for Alzheimer's disease. Twenty middle-aged women underwent resting state functional magnetic resonance imaging. Subjects were dichotomized relative to fasting plasma insulin levels (i.e., > 8 ?IU/mL [n = 10] and < 8 ?IU/mL [n = 10]), and functional connectivity analysis contrasted their respective blood oxygen level-dependent signal correlation between DMN and hippocampal regions. Higher-insulin women had significantly reduced positive associations between the medial prefrontal cortex and bilateral parahippocampal regions extending to the right hippocampus, and conversely, between the left and right hippocampus and medial prefrontal cortex. Neuropsychological data (all within normal ranges) also showed significant differences with respect to executive functioning and global intelligence. The results provide further evidence of deleterious effects of IR on the hippocampus and cognition. Further imaging studies of the IR-related perturbations in DMN-hippocampal functional connectivity are needed.
View details for DOI 10.1016/j.neurobiolaging.2012.06.006
View details for Web of Science ID 000313117900001
View details for PubMedID 22770543
Differences in Verbal Memory Performance in Postmenopausal Women Receiving Hormone Therapy: 17 beta-Estradiol Versus Conjugated Equine Estrogens
AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
2011; 19 (9): 792-802
Insulin resistance (IR) is the main pathological condition underlying vascular disorders, such as diabetes and cardiovascular disease, which are well established risk factors for cognitive decline and Alzheimer disease (AD). Hippocampal atrophy has been associated with cognitive decline, but little is known about the influence of IR on hippocampus integrity in non-diabetic, cognitively intact individuals. Herein, 50 women ages 50-65, current users of hormone therapy, underwent magnetic resonance imaging, cognitive testing, and homeostatic assessment of insulin resistance (HOMA-IR), as part of a longitudinal study examining brain structure and function in postmenopausal women at risk for AD. Results demonstrated a significant negative relationship between HOMA-IR and right and total hippocampal volume, overall cognitive performance, and selective tests of verbal and non-verbal memory. The main effect of HOMA-IR on brain structure and cognition was not altered by the presence of APOE-?4 allele or by reproductive history, such as duration of endogenous and exogenous estrogen exposure. These results suggest that IR in middle-aged individuals at risk for AD may be biomarker for dementia risk.
View details for DOI 10.1016/j.neurobiolaging.2009.12.005
View details for Web of Science ID 000295220700003
View details for PubMedID 20031276
Rosiglitazone Add-On in Treatment of Depressed Patients with Insulin Resistance: a Pilot Study
2010; 10: 321-328
Much controversy exists and many questions remain unanswered about the effects of hormone therapy (HT) on cognition in postmenopausal women. There is growing evidence suggesting that HT compounds containing conjugated equine estrogen (CEE) have negative effects on cognition whereas 17?-estradiol (17?-E) either has positive or neutral effects. The present study sought to further examine this issue in a sample of postmenopausal women with risk factors for Alzheimer's disease (AD).Cross-sectional neuropsychological evaluation.Academic research clinic.68 healthy postmenopausal women (aged 49-68) receiving either 17?-E or CEE for at least one year with increased risk for AD.Neuropsychological test battery of the cognitive domains of attention/working memory/processing speed, verbal memory, visual memory, and executive functioning.Multivariate analyses of variance (MANOVA) showed significantly better verbal memory performance in women receiving 17?-E compared to women receiving CEE regardless of age, IQ, years of education, risk factors for AD (including APOE-?4 carriership), duration of endogenous and exogenous estrogen exposure, concurrent progesterone use, or natural versus surgical menopause status.Verbal memory performance was better in postmenopausal women receiving 17?-E compared to CEE in a sample population of women with risk factors for AD. Genetic risk for AD as well as other confounds did not affect this finding. The results suggest a differential effect of HT type on verbal memory, with 17?-E being a preferential compound. Further evaluation of HT types, regimens and duration of use on cognitive performance in postmenopausal women in a controlled longitudinal design is warranted.
View details for DOI 10.1097/JGP.0b013e3181ff678a
View details for Web of Science ID 000294415800006
View details for PubMedID 21873835
Cognitive effects of memantine in postmenopausal women at risk of dementia: a pilot study
ACTA NEUROLOGICA SCANDINAVICA
2009; 119 (3): 172-179
A number of cross-sectional studies have suggested an association between insulin resistance (IR) and affective disorders. However, limited data exist on potential changes in IR in a prospective treatment of depression. The present pilot study tested the hypothesis that improvement of IR with the addition of an insulin-sensitizing agent would improve mood in nondiabetic patients with unipolar or bipolar depression, who had surrogate blood markers suggestive of IR. Surrogate IR-criteria blood markers were fasting plasma glucose >100 mg/dl or triglyceride (TG) to high density lipoprotein (HDL) ratio >3.0. Open-label rosiglitazone, titrated to a dose of 8 mg/day, was administered for 12 weeks to 12 patients with depressive disorder receiving treatment as usual (TAU). Eight patients who completed the 12-week study exhibited significant declines in both depression severity by the Hamilton Depression Rating Scale and the Clinical Global Impression scale, with moderate effect sizes noted. Modest improvement in Matsuda Index scores was also noted at 12 weeks, yet declines in depression severity scores were not associated with improvements in the endocrine markers (Matsuda Index, TG/HDL ratio, and body mass index). These results suggest the potential novel use for an insulin-sensitizing agent in the treatment of depressive disorders. Larger placebo-controlled studies are warranted.
View details for DOI 10.1100/tsw.2010.32
View details for Web of Science ID 000274935000007
View details for PubMedID 20191245
Estrogen and response to sertraline in postmenopausal women with major depressive disorder: A pilot study
JOURNAL OF PSYCHIATRIC RESEARCH
2007; 41 (3-4): 338-343
To determine the effects of memantine on cognition in a normal population of postmenopausal women with putative risk factors for Alzheimer's disease (AD) using a built-in control for the genetic risk factor for AD (apoE-epsilon4 status).A prospective, open-label, 6-month pilot medication trial with memantine and follow-up after discontinuance conducted at the Center for Neuroscience in Women's Health, Stanford University School of Medicine. Neuropsychological data were collected on 22 community-dwelling postmenopausal women (11 apoE-epsilon4 carriers and 11 apoE-epsilon4 non-carriers) with at least one putative risk factor for AD.ApoE-epsilon4 status was not a significant predictor of change in neuropsychological performance. Changes associated with memantine treatment for entire sample included significant declines in some variables associated with verbal learning and memory that improved upon medication withdrawal. A positive medication effect was noted with executive functions and possibly category fluency. Trend-level improvements were seen in motor dexterity of the non-dominant hand and maintained even after drug discontinuance.Treatment with memantine appeared to have differential effects on cognitive performance in a population of women with putative risk factors for AD. ApoE-epsilon4 carrier status did not account for observed changes in cognition.
View details for DOI 10.1111/j.1600-0404.2008.01084.x
View details for Web of Science ID 000262949100005
View details for PubMedID 18705678
Mood and neuropsychological changes in women with midlife depression treated with escitalopram
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
2006; 26 (4): 361-366
Pilot study examining the effects of estrogen therapy (ET) on antidepressant response in postmenopausal women with major depressive disorder (MDD).Twenty-two subjects received sertraline at 50mg/day for one week, with an increase to 100mg/day at week 2 for a 10-week trial. Transdermal estrogen or placebo patches 0.1mg were randomly administered concurrent with the initiation of sertraline treatment. The 21 item Hamilton Depression Rating Scale (HDRS-21) was administered to all patients at baseline and weekly thereafter.Both groups showed a similar significant reduction in HDRS-21 scores by the end of the study. There was no significant difference between the two treatment groups at the end of the 10-week trial, but the women receiving sertraline with ET showed significantly greater early improvement (weeks 2-4) compared to the women receiving sertraline with placebo.Sertraline is an effective antidepressant for postmenopausal women with MDD. ET does not alter the response rate to antidepressant therapy however ET may play a role in accelerating the antidepressant response.
View details for DOI 10.1016/j.jpsychires.2006.03.009
View details for Web of Science ID 000243214000019
View details for PubMedID 16697413
This study assessed mood and neuropsychological function in a population of middle-aged women with major depressive disorder treated with escitalopram.Psychometric data measuring severity of depression were collected from 19 women and neuropsychological data were collected from 17 women aged between 45 and 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of major depression in a study in the Behavioral Neuroendocrinology Program at the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine. All women were treated with escitalopram in an open-label design. Mean age was 55.94 years and mean number of years of education was 16.36 years. Diagnosis of major depressive disorder was assessed with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and mood was evaluated with the 21-item Hamilton Depression Rating Scale (HAM-D) at baseline and at weekly follow-ups for 12 weeks. Cognition was assessed at baseline and 3 months after treatment using a neuropsychological test battery, which included an abbreviated measure of Full Scale Intelligence Quotient, measures of attention and processing speed, verbal and nonverbal memory, executive functioning, and verbal fluency. Self-report data were collected on current menopause status and current hormone therapy use in the postmenopausal women. Paired sample t tests were used to analyze the change in total HAM-D scores and neuropsychological variables.Statistically significant improvements were found in total HAM-D score, Wechsler Memory Scale III Logical Memory 1st Recall, I, and II scores, Wechsler Memory Scale III Visual Reproduction I scores, and Trail Making Test Part B scores. There was a statistically significant decrease in Controlled Oral Word Association Test FAS scores.Treatment of depression with escitalopram in a population of middle-aged women was shown to improve mood and cognitive efficiency in complex attention, short- and long-term recall of contextual information, short-term recall of visual information, and cognitive flexibility; however, it was shown to worsen phonemic fluency.
View details for DOI 10.1097/01.jcp.0000227699.26375.f8
View details for Web of Science ID 000239551200003
View details for PubMedID 16855452