Sex-related differences in the prevalence of cognitive impairment among overweight and obese adults with type 2 diabetes.
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ABSTRACT:
SUBMITTER: Espeland MA
PROVIDER: S-EPMC6338071 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
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Project description:IntroductionIt is unknown whether rates of cognitive decline differ between older women and men with type 2 diabetes (T2D) and overweight or obesity.MethodsTwo to four cognitive assessments were obtained across up to 10 years from 2799 adults (mean age 68 years; 62% women) with T2D who had been enrolled in a clinical trial of weight loss intervention. Sex-related differences in means and rates of decline of cognitive scores were assessed.ResultsWomen outperformed men in verbal learning and processing speed (P < 0.001), but not executive function (P = 0.22). The rates of decline over time for women and men were similar (P ≥ 0.10); however women, but not men, with apolipoprotein E (APOE) ε4 alleles had steeper declines in verbal learning (P = 0.02) and processing speed (P = 0.007) than those without these alleles.DiscussionCognitive advantages for women with T2D and overweight/obesity over men are preserved as they age; however, these are eroded by the APOE ε4 genotype.
| S-EPMC8033410 | biostudies-literature
Project description:In overweight/obese individuals, cardiometabolic risk factors differ by race and sex categories. Small-molecule metabolites and metabolic hormone levels might also differ across these categories and contribute to risk factor heterogeneity. To explore this possibility, we performed a cross-sectional analysis of fasting plasma levels of 69 small-molecule metabolites and 13 metabolic hormones in 500 overweight/obese adults who participated in the Weight Loss Maintenance trial. Principal-components analysis (PCA) was used for reduction of metabolite data. Race and sex-stratified comparisons of metabolite factors and metabolic hormones were performed. African Americans represented 37.4% of the study participants, and females 63.0%. Of thirteen metabolite factors identified, three differed by race and sex: levels of factor 3 (branched-chain amino acids and related metabolites, p<0.0001), factor 6 (long-chain acylcarnitines, p<0.01), and factor 2 (medium-chain dicarboxylated acylcarnitines, p<0.0001) were higher in males vs. females; factor 6 levels were higher in Caucasians vs. African Americans (p<0.0001). Significant differences were also observed in hormones regulating body weight homeostasis. Among overweight/obese adults, there are significant race and sex differences in small-molecule metabolites and metabolic hormones; these differences may contribute to risk factor heterogeneity across race and sex subgroups and should be considered in future investigations with circulating metabolites and metabolic hormones.
| S-EPMC3837434 | biostudies-literature
Project description:OBJECTIVE:We determined whether there are sex differences in the prevalence and profile of HIV-associated neurocognitive impairment, and whether sex moderates the effect of HIV-serostatus on neurocognitive impairment among HIV-positive and HIV-negative individuals. Secondarily, we assessed whether differences were explained by greater biopsychosocial risk factors in HIV-positive women. DESIGN:An observational cohort study. METHODS:Analyses included 1361 HIV-positive (204 women) and 702 HIV-negative (214 women) (ages?=?18-79 years) participants from the UCSD HIV Neurobehavioral Research Program. Demographically corrected standardized T-scores from 15 neuropsychological tests were used to calculate domain-specific and global deficit scores (GDS). GDS at least 0.5 defined neurocognitive impairment. Biopsychosocial risk factors included low education, low reading level (education quality), lifetime substance use disorders, depressed mood (clinically significant depressive symptoms and/or current major depressive disorder) and a cumulative syndemic count (sum of biopsychosocial risk factors, range?=?0-4). Race-stratified analyses were conducted. Analyses were adjusted for relevant demographic and clinical factors. RESULTS:HIV-associated neurocognitive impairment was more prevalent in women versus men; however, the difference was eliminated after adjustment for reading level. In sex-stratified logistic regressions, the association between HIV-seropositivity and higher likelihood of neurocognitive impairment was stronger in women versus men; however, the association was attenuated in women, but not men, after adjusting for reading level. These results in the overall sample were specific to blacks. Sex differences in the profile of HIV-associated neurocognitive impairment varied by race. CONCLUSION:Women, particularly black women, were most at-risk for HIV-associated neurocognitive impairment. Higher rates of HIV-associated neurocognitive impairment in women versus men may reflect differences in educational quality.
| S-EPMC6396274 | biostudies-literature
Project description:BACKGROUND:Sex may be an important modifier of brain health in response to risk factors. We compared brain structure and function of older overweight and obese women and men with type 2 diabetes mellitus. METHODS:Cross-sectional cognitive assessments and magnetic resonance images were obtained in 224 women and 95 men (mean age 69 years) with histories of type 2 diabetes mellitus and overweight or obesity. Prior to magnetic resonance images, participants had completed an average of 10 years of random assignment to either multidomain intervention targeting weight loss or a control condition of diabetes support and education. Total (summed gray and white) matter volumes, white matter hyperintensity volumes, and cerebral blood flow across five brain regions of interest were analyzed using mixed-effects models. RESULTS:After covariate adjustment, women, compared with men, averaged 10.9 [95% confidence interval 3.3, 18.5; ?1%] cc greater summed region of interest volumes and 1.39 [0.00002, 2.78; ?54%] cc greater summed white matter hyperintensity volumes. Sex differences could not be attributed to risk factor profiles or intervention response. Their magnitude did not vary significantly with respect to age, body mass index, intervention assignment, or APOE-?4 genotype. Sex differences in brain magnetic resonance images outcomes did not account for the better levels of cognitive functioning in women than men. CONCLUSIONS:In a large cohort of older overweight or obese adults with type 2 diabetes mellitus, differences in brain volumes and white matter disease were apparent between women and men, but these did not account for a lower prevalence of cognitive impairment in women compared with men in this cohort. TRIAL REGISTRATION:NCT00017953.
| S-EPMC7205422 | biostudies-literature
Project description:Studies have shown differences in specific cognitive ability domains and risk of Alzheimer's disease between the men and women at later age. However it is important to know that sex differences in cognitive function during adulthood may have their basis in both organizational effects, i.e., occurring as early as during the neuronal development period, as well as in activational effects, where the influence of the sex steroids influence brain function in adulthood. Further, the rate of cognitive decline with aging is also different between the sexes. Understanding the biology of sex differences in cognitive function will not only provide insight into Alzheimer's disease prevention, but also is integral to the development of personalized, gender-specific medicine. This review draws on epidemiological, translational, clinical, and basic science studies to assess the impact of sex differences in cognitive function from young to old, and examines the effects of sex hormone treatments on Alzheimer's disease in men and women.
| S-EPMC4087048 | biostudies-literature
Project description:The relationship between body weight changes in late life and cognitive function is controversial.We investigated whether weight gain or loss in late life affected cognitive function in community-dwelling older adults over a 3-year period.Our study used data from the Survey of Living Conditions and Welfare Needs of Korean Older Persons and included 3859 subjects (aged ?65 years) with normal cognition at baseline. At baseline and the 3-year follow-up, body weight and height were measured, and cognitive function was assessed using the mini-mental state examination. Based on their body mass index (BMI) at baseline and follow-up, we divided the subjects into 4 groups: weight gain (baseline BMI <23?kg/m and follow-up BMI ?23?kg/m); weight loss (baseline BMI ?23?kg/m and follow-up BMI <23?kg/m); stable overweight/obese (BMI ?23?kg/m at both visits); and stable non-overweight/obese (BMI <23?kg/m at both visits). Incidence rates (IRs) of cognitive impairment per 100 persons and IR ratios (IRRs) were calculated for each group and adjusted for confounding variables.At the 3-year follow-up, 610 cases of cognitive impairment (15.8%) were identified. The stable overweight/obese group had the lowest IR (14.0, 95% confidence interval [CI] 12.45-15.71) and was therefore used as the reference group when calculating IRRs for cognitive impairment. When men and women were evaluated separately, IRs between groups were significantly different only for women. The stable non-overweight/obese group (IRR 1.65, 95% CI 1.22-2.22) and the weight gain group (IRR 1.93, 95% CI 1.24-3.01) had higher IRs than those in the stable overweight/obese group. As a gain or loss of adiposity, the IR of the weight gain group (IRR 1.17, 95% CI 0.74-1.84) was not different from that of the stable non-overweight/obese group. Also, the IR of weight loss group (IRR 1.09, 95% CI 0.71-1.67) was not significantly different from that of the stable overweight/obese group.We suggest that overweight or obese older women at baseline had cognitive benefits. However, additional gain or loss of adiposity in late life did not affect the risk of cognitive impairment.
| S-EPMC6831333 | biostudies-literature
Project description:Cognitive dysfunction has been accepted as a possible complication of type 2 diabetes (T2D), but few studies revealed the potential roles of Long non‑coding RNAs (lncRNAs) in cognitive dysfunction in T2D. The purpose of the current research is to demonstrate the specific expression patterns of lncRNA-mRNA in the hippocampi of T2D db/db mice exhibiting cognitive impairment. In this study, the results from behavioral tests showed that T2D db/db mice displayed short-term and spatial working memory deficits compared to db/m mice. Furthermore, western blot analysis demonstrated that compared with db/m mice, p-GSK3β (ser9) protein levels were markedly elevated in T2D db/db mice (P<0.01). In addition, though not statistically significant, the ratio of p-Tau (Ser396) to Tau 46, α-Synuclein expression and p-GSK3α (ser21) expression were also relatively higher in T2D db/db mice than in db/m mice. The microarray profiling revealed that 75 lncRNAs and 26 mRNAs were obviously dysregulated in T2D db/db mice (>2.0 fold change, P<0.05). GO analysis demonstrated that the differentially expressed mRNAs participated in immune response, extracellular membrane-bounded organelle and extracellular region. KEGG analysis revealed that the differentially expressed mRNAs were mainly involved in one carbon pool by folate, glyoxylate and dicarboxylate metabolism, autophagy, glycine, serine and threonine metabolism and B cell receptor signaling pathway. An lncRNA‑mRNA coexpression network containing 71 lncRNAs and 26 mRNAs was built to investigate the interaction between lncRNA and mRNA. Collectively, these results revealed the differential hippocampal expression profiles of lncRNAs in T2D mice with cognitive dysfunction, and the findings from this study provide new clues for exploring the potential roles of lncRNAs in the pathogenesis of cognitive dysfunction in T2D.
2020-06-02 | GSE151294 | GEO
Project description:ImportanceSex differences in dementia risk are unclear, but some studies have found greater risk for women.ObjectiveTo determine associations between sex and cognitive decline in order to better understand sex differences in dementia risk.Design, setting, and participantsThis cohort study used pooled analysis of individual participant data from 5 cohort studies for years 1971 to 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Linear mixed-effects models were used to estimate changes in each continuous cognitive outcome over time by sex. Data analysis was completed from March 2019 to October 2020.ExposureSex.Main outcomes and measuresThe primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition.ResultsAmong 34 349 participants, 26 088 who self-reported Black or White race, were free of stroke and dementia, and had covariate data at or before the first cognitive assessment were included for analysis. Median (interquartile range) follow-up was 7.9 (5.3-20.5) years. There were 11 775 (44.7%) men (median [interquartile range] age, 58 [51-66] years at first cognitive assessment; 2229 [18.9%] Black) and 14 313 women (median [interquartile range] age, 58 [51-67] years at first cognitive assessment; 3636 [25.4%] Black). Women had significantly higher baseline performance than men in global cognition (2.20 points higher; 95% CI, 2.04 to 2.35 points; P < .001), executive function (2.13 points higher; 95% CI, 1.98 to 2.29 points; P < .001), and memory (1.89 points higher; 95% CI, 1.72 to 2.06 points; P < .001). Compared with men, women had significantly faster declines in global cognition (-0.07 points/y faster; 95% CI, -0.08 to -0.05 points/y; P < .001) and executive function (-0.06 points/y faster; 95% CI, -0.07 to -0.05 points/y; P < .001). Men and women had similar declines in memory (-0.004 points/y faster; 95% CI, -0.023 to 0.014; P = .61).Conclusions and relevanceThe results of this cohort study suggest that women may have greater cognitive reserve but faster cognitive decline than men, which could contribute to sex differences in late-life dementia.
| S-EPMC7907956 | biostudies-literature
Project description:Islet autoantibodies are typically associated with type 1 diabetes, but have been found in patients diagnosed with type 2 diabetes in whom they are associated with lower adiposity. The significance of autoantibody positivity in overweight and obese patients is not well understood. The aim of this study was to determine the prevalence and clinical significance of islet autoantibodies in overweight/obese adults diagnosed with type 2 diabetes. This study includes 204 participants at one site of the multicenter Look AHEAD (Action for Health in Diabetes) trial (ClinicalTrials.gov identifier: NCT00017953) which randomized overweight/obese adults diagnosed with type 2 diabetes to an intensive lifestyle intervention or diabetes support and education. We measured antibodies to glutamic acid decarboxylase, insulinoma antigen-2, and zinc transporter 8. Participants with and without autoantibodies were compared with respect to baseline clinical features, and longitudinal changes in weight, hemoglobin A1c, and antihyperglycemic medications. We found that 13 participants (6.4%) were autoantibody positive, including six of 47 participants (12.8%) with BMI ?40?kg/m2. At baseline, autoantibody positive participants had higher HDL cholesterol (1.27 vs. 1.09?mmol/L, p?=?.034) and lower fasting C-peptide (0.32 vs. 0.57?nmol/L, p?=?.049). Over four years, autoantibody positive participants lost 5.1?kg more weight than autoantibody negative participants (p?=?.056). Longitudinal changes in hemoglobin A1c did not differ by autoantibody status, though autoantibody positive participants were more likely to increase the number of antihyperglycemic medications or initiate insulin (p?=?.011). In conclusion, islet autoantibodies were present in 6.4% of overweight/obese adults with type 2 diabetes including those with severe obesity, and were associated with distinct clinical features. The effect of autoantibody positivity on weight loss interventions requires further study.
| S-EPMC6362362 | biostudies-literature
Project description:Objective: We aimed to test the hypothesis that elevated neocortical β-amyloid (Aβ), a hallmark feature of Alzheimer's disease (AD), predicts sex-specific cognitive trajectories in clinically normal older adults, with women showing greater risk of decline than men. Method: Florbetapir Aβ positron emission tomography (PET) was acquired in 149 clinically normal older adults (52% female, Mage = 74). Participants underwent cognitive testing at baseline and during annual follow-up visits over a timespan of up to 5.14 years. Mixed-effects regression models evaluated whether relations between baseline neocortical Standardized Uptake Value Ratio (SUVR) and composite scores of episodic memory, executive functioning, and processing speed were moderated by sex (male/female) and apolipoprotein E (APOE) status (ε4 carrier/noncarrier). Results: Higher baseline SUVR was associated with longitudinal decline in episodic memory in women (b = -1.32, p < .001) but not men (b = -0.30, p = .28). Female APOE ε4 carriers with elevated SUVR showed particularly precipitous declines in episodic memory (b = -4.33, p < .001) whereas other cognitive domains were spared. SUVR did not predict changes in executive functioning or processing speed, regardless of sex (ps >.63), though there was a main effect of SUVR on processing speed (b = 2.50, p = .003). Conclusions: Clinically normal women with elevated Aβ are more vulnerable to episodic memory decline than men. Understanding sex-related differences in AD, particularly in preclinical stages, is crucial for guiding precision medicine approaches to early detection and intervention. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
| S-EPMC7839841 | biostudies-literature