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Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5-22.4 kg/m2 ), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m2 ) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non-linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.

ObjectivesRelatively few APOE ε4+ carriers survive to old age (age 80+) without cognitive impairment (CI); thus, little is known about distinguishing characteristics of resilient APOE ε4+ carriers. Herein, we describe the sociodemographic characteristics of a large sample of resilient APOE ε4+ women from the Women's Health Initiative Memory Study (WHIMS) and compare them to noncarriers and APOE ε4+ women who developed CI before age 80.MethodsWomen were recruited for clinical trials evaluating postmenopausal hormone therapy and incidence of dementia. During posttrial follow-up, cognitive status was adjudicated annually. Among 5716 women, we compared groups by APOE ε4 status using logistic regression, covarying for treatment, demographics, lifestyle, cardiovascular and physical function, well-being, and self-rated general health.ResultsAmong 557 APOE ε4+ women, those who survived to age 80+ without CI had higher baseline self-rated general health (odds ratio [OR]: 1.02; 95% confidence interval [CI], 1.01-1.04) and cognitive scores (OR: 1.18; 95% CI, 1.12-1.25) than those who did not reach age 80 without CI. Baseline high total cholesterol and low-density lipoprotein (LDL) levels were similar across APOE ε4+ groups but were higher compared with APOE ε4- women. Among women who survived to 80+ without CI, more APOE ε4+ women had a history of high total cholesterol (P = .003) and LDL cholesterol (OR: 1.01; 95% CI, 1.00-1.01). There were no differences in hypertension, diabetes, or other vascular risk factors in APOE ε4+ women compared with noncarriers.ConclusionsResults highlight the importance of baseline cognitive function and general health for late-life cognition among ε4+ women.

ObjectivesTo examine whether trajectories of global cognitive function over time in studies that change assessment protocols may be modeled based on an individual's performance relative to others in the study cohort.DesignExtended follow-up of a cohort originally enrolled in a clinical trial of postmenopausal hormone therapy.SettingThe Women's Health Initiative Memory Study switched from an in-person interview with the Modified Mini-Mental State Examination to a telephone-based interview with the modified Telephone Interview for Cognitive Status to assess global cognitive function over long-term follow-up.ParticipantsWomen aged 75 to 92 (N=2,561).MeasurementsAnnual cognitive assessments from participants, ranked according to age-, race- and ethnicity-adjusted performance levels, were used to identify distinct trajectories. Participants assigned to the resulting trajectories were compared for selected risk factor profiles.ResultsOur approach grouped participants into five trajectories according to relative cognitive performance over time. These groups differed significantly according to 3 known risk factors for cognitive decline-education level, apolipoprotein E-ϵ4 genotype, and type 2 diabetes mellitus-and a biomarker based on brain structure that has been linked to cognitive decline and Alzheimer's disease. Participants with consistently low relative levels of cognitive function over time and those whose relative performance over time declined to these levels tended to have poorer risk factor profiles.ConclusionLongitudinal measures of an individual's relative performance on different assessment protocols for global cognitive function can be used to identify trajectories of change over time that appear to have internal validity with respect to known risk factors.

BackgroundCognitive impairment and decline may signal the increased risk of incident cardiovascular disease (CVD). We examined associations of global cognitive function, as measured by the Modified Mini-Mental State Examination (3MS) and changes in 3MS over time, with incident CVD, individual CVD outcomes, CVD death, and all-cause mortality.MethodsA total of 5,596 women (≥ 60) from the Women's Health Initiative Memory Study free of CVD at baseline were followed for an average of 7.1 years. The 3MS was measured at baseline and annually thereafter. Cox proportional hazards regressions were used to model associations between baseline 3MS and changes in 3MS and time to events.ResultsIn the fully-adjusted models for every 5-point lower baseline 3MS score, the risk was 12% greater for incident CVD, 37% for HF, 35% for CVD death, and 24% for all-cause mortality. No significant relationships were found for coronary heart disease (CHD), angina, stroke/transient ischemic attack (TIA), or coronary revascularization. When change in 3MS was added as a time-varying covariate in the fully-adjusted models, for every 1-point/year greater decline in 3MS, the risk was 4% greater for incident CVD, 10% for CHD, 9% for Stroke/TIA, 17% for CVD death, and 13% for all-cause mortality.ConclusionsIn older women free of prevalent CVD at baseline, lower baseline global cognitive function or decline in global cognitive function over time, increased risk of incident CVD, CVD death, and all-cause mortality.

Studies on the relationship of cholesterol concentrations and lipid-lowering medications with dementia risk have yielded inconsistent findings. Therefore, we investigated the association of lipid concentrations and lipid-lowering medications with cognitive function in the Multi-Ethnic Study of Atherosclerosis across 3 different cognitive domains assessed by means of the Cognitive Abilities Screening Instrument (CASI; version 2), the Digit Symbol Coding (DSC) Test, and the Digit Span (DS) Test in 2010-2012. After adjustment for sociodemographic and confounding factors, including concentrations of other lipids and use of lipid-lowering medication, higher total cholesterol, low-density lipoprotein cholesterol, and non-high-density-lipoprotein cholesterol concentrations were modestly associated with higher DS Test scores. None of the lipid parameters were associated with CASI or DSC Test scores. Similarly, changes in lipid concentrations were not associated with any cognitive function test score. Using treatment effects model analysis and after adjusting for confounding factors, including lipid concentrations, the use of any lipid-lowering medication, especially statins, was associated with higher scores on the CASI and backward DS tests but not on the DSC and forward DS tests. Our study does not support a robust association between lipid concentrations and cognitive function or between the use of lipid-lowering medication, especially statins, and worse cognitive function.

IntroductionWe investigated the association between age of onset of hypertension and dementia risk in an oldest-old cohort.MethodsParticipants are from The 90+ Study, a population-based longitudinal study of people aged 90+ who are survivors from the Leisure World Cohort Study. We estimated hypertension onset age using self-reported information from The 90+ Study and Leisure World Cohort Study, collected about 20 years earlier. A total of 559 participants without dementia were followed every 6 months for up to 10 years.ResultsA total of 224 participants developed dementia during follow-up (mean = 2.8 years). Compared with those without hypertension, participants whose hypertension onset age was 80 to 89 years had a lower dementia risk (hazard ratio = 0.58, P = .04) and participants with an onset age of 90+ years had the lowest risk (hazard ratio = 0.37, P = .004).DiscussionDeveloping hypertension at older ages may protect against dementia. Understanding the mechanisms for this lower risk is important for determining ways to prevent dementia in the very elderly.

ObjectiveType 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a meta-analysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia.Research design and methodsA systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex-specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random-effects meta-analyses.ResultsStudy-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple-adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45-1.80]; men: pooled RR 1.58 [95% CI 1.38-1.81]). The diabetes-associated RRs for vascular dementia were 2.34 (95% CI 1.86-2.94) in women and 1.73 (95% CI 1.61-1.85) in men, and for nonvascular dementia, the RRs were 1.53 (95% CI 1.35-1.73) in women and 1.49 (95% CI 1.31-1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08-1.30]; P < 0.001).ConclusionsIndividuals with type 2 diabetes are at ∼60% greater risk for the development of dementia compared with those without diabetes. For vascular dementia, but not for nonvascular dementia, the additional risk is greater in women.

Background: Risk factors for cognitive decline and physical decline have been studied independently, however older adults might experience decline in both areas i.e., dual decline. Risk factors associated with dual decline are largely unknown and have significant implications on health outcomes. The aim of this study is to explore risk factors associated with dual decline. Methods: Using data from the Health, Aging and Body Composition (Health ABC) study, a longitudinal prospective cohort study, we examined trajectories of decline based on repeated measures of the Modified Mini-Mental State Exam (3MSE) and the Short Physical Performance Battery (SPPB) across 6 years (n=1,552). We calculated four mutually exclusive trajectories of decline and explored predictors of decline: cognitive decline (n = 306) = lowest quartile of slope on the 3MSE or 1.5 SD below mean at baseline, physical decline (n = 231) = lowest quartile of slope on the SPPB or 1.5 SD below mean at baseline, dual decline (n = 110) = lowest quartile in both measures or 1.5 SD below mean in both measures at baseline. Individuals who did not meet criteria for one of the decline groups were classified as the reference group. (n= 905). Results: Multinomial logistic regression tested the association of 17 baseline risk factors with decline. Odds of dual decline where significantly higher for individuals at baseline with depressive symptoms (CES-D >16) (Odds Ratio (OR)=2.49, 95% Confidence Interval (CI): 1.05-6.29), ApoE-e4 carrier (OR= 2.09, 95% CI: 1.06-1.95), or if individuals had lost 5+lbs in past year (OR=1.79, 95% CI: 1.13-2.84). Odds were significantly lower for individuals with a higher score on the Digit Symbol Substitution Test per standard deviation (OR per SD: 0.47, 95% CI 0.36-0.62) and faster 400-meter gait (OR per SD= 0.49, 95% CI: 0.37-0.64). Conclusion: Among predictors, depressive symptoms at baseline significantly increased the odds of developing dual decline but was not associated with decline in the exclusively cognitive or physical decline groups. APOE-e4 status increased the odds for cognitive decline and dual decline but not physical decline. More research on dual decline is needed because this group represents a high risk, vulnerable subset of older adults. [ABSTRACT FROM AUTHOR]

Background Vascular risk scores are associated with incident dementia. Information regarding their association with cognitive performance and decline in racially/ethnically diverse cohorts is lacking. Method In 4 392 Multi-Ethnic Study of Atherosclerosis participants (aged 60.1 ± 9.4 years; 53% women; 41% White, 11% Chinese American, 26% African American, 21% Hispanic), we compared associations of Exam 1 (2000–2002) Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE), Framingham Stroke Risk Profile (FSRP), and atherosclerotic cardiovascular disease pooled cohort equation (ASCVD-PCE) risk scores with Exam 5 (2010–2012) Cognitive Abilities Screening Instrument (CASI), Digit Symbol Coding (DSC), and Digit Span (DS) cognitive test performance using multivariable linear regression, and examined racial/ethnic interactions. In 1 838 participants with repeat CASI data at Exam 6 (2016–2018), we related risk scores to odds of a 1- SD decline in CASI performance using multivariable logistic regression. Results SD increments in each risk score were associated with worse cognitive performance. CAIDE had stronger associations with CASI performance than the FSRP and ASCVD-PCE, but associations of ASCVD-PCE with the DSC and DS were similar to CAIDE (difference in β [95% CI] = −0.57 [−1.48, 0.34] and −0.21 [−0.43, 0.01], respectively). Race/ethnicity modified associations. For example, associations between CAIDE and CASI were greater in African Americans and Hispanics than in Whites (difference in β = 0.69 [0.02, 1.36] and 1.67 [0.95, 2.39], respectively). Risk scores were comparably associated with decline in CASI performance. Conclusions Antecedent vascular risk scores are associated with cognitive performance and decline in the 4 most common U.S. racial/ethnic groups, but associations differ among risk scores and by race/ethnicity. [ABSTRACT FROM AUTHOR]

Background: A small but growing body of evidence supports a relationship between neighborhood socioeconomic status (NSES) and cognitive decline. Additional work is needed to characterize this relationship controlling for risk factors such as cardiovascular, cerebrovascular, and genetic risk factors. Methods: Cognitive decline was assessed in association with NSES, and cardiovascular and cerebrovascular risk factors (heart disease, diabetes, hypertension, and stroke) in 8,198 individuals from the 1992–2010 waves of the Health and Retirement Study (HRS). Latent class trajectory analysis determined the number of cognitive trajectory classes that best fit the data, and a multinomial logistic regression model in the latent class framework assessed the risk for cognitive classes conferred by NSES index score and heart disease, diabetes, hypertension, and stroke across three trajectory classes of cognitive function. The analyses controlled for genetic risk for cognitive decline (including APOE genotype) and demographic variables, including education. Results: The HRS sample was 57.6% female and 85.5% White, with a mean age of 67.5(3.5) years at baseline. The three-quadratic-class model best fit the data, where higher classes represented better cognitive function. Those with better cognitive function were mainly younger white females. Those in the highest quartile of NSES had 57% higher odds of being in the high cognitive function class. Heart disease, diabetes, hypertension, and stroke each increased the odds having of lower cognitive function. Conclusions: In examining the relationship of cognitive status with various variables, neighborhood socioeconomic status, cardiovascular risk, and cerebrovascular risk persisted across the cognitive trajectory classes. [ABSTRACT FROM AUTHOR]

Objectives Genetic risks for cognitive decline are not modifiable; however their relative importance compared to modifiable factors is unclear. We used machine learning to evaluate modifiable and genetic risk factors for Alzheimer's disease (AD), to predict cognitive decline. Methods Health and Retirement Study participants, aged 65–90 years, with DNA and >2 cognitive evaluations, were included (n = 7,142). Predictors included age, body mass index, gender, education, APOE ε4, cardiovascular, hypertension, diabetes, stroke, neighborhood socioeconomic status (NSES), and AD risk genes. Latent class trajectory analyses of cognitive scores determined the form and number of classes. Random Forests (RF) classification investigated predictors of cognitive trajectories. Performance metrics (accuracy, sensitivity, and specificity) were reported. Results Three classes were identified. Discriminating highest from lowest classes produced the best RF performance: accuracy = 78% (1.0%), sensitivity = 75% (1.0%), and specificity = 81% (1.0%). Top ranked predictors were education, age, gender, stroke, NSES, and diabetes, APOE ε4 carrier status, and body mass index (BMI). When discriminating high from medium classes, top predictors were education, age, gender, stroke, diabetes, NSES, and BMI. When discriminating medium from the low classes, education, NSES, age, diabetes, and stroke were top predictors. Discussion The combination of latent trajectories and RF classification techniques suggested that nongenetic factors contribute more to cognitive decline than genetic factors. Education was the most relevant predictor for discrimination. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes mellitus and obesity may increase risks for cognitive decline as individuals age. It is unknown whether this results in different prevalences of cognitive impairment for women and men. Methods: The Action for Health in Diabetes, a randomized controlled clinical trial of a 10‐year intensive lifestyle intervention, adjudicated cases of cross‐sectional cognitive impairment (mild cognitive impairment or dementia) 10–13 years after enrollment in 3802 individuals (61% women). Results: The cross‐sectional prevalences of cognitive impairment were 8.3% (women) and 14.8% (men): adjusted odds ratio 0.55, 95% confidence interval [0.43, 0.71], P <.001. Demographic, clinical, and lifestyle risk factors varied between women and men but did not account for this difference, which was limited to individuals without apolipoprotein E (APOE)‐ε4 alleles (interaction P =.034). Conclusions: Among overweight and obese adults with type 2 diabetes mellitus, traditional risk factors did not account for the lower prevalence of cognitive impairment observed in women compared with men. [ABSTRACT FROM AUTHOR]

Introduction We investigated the association between age of onset of hypertension and dementia risk in an oldest-old cohort. Methods Participants are from The 90+ Study , a population-based longitudinal study of people aged 90+ who are survivors from the Leisure World Cohort Study. We estimated hypertension onset age using self-reported information from The 90+ Study and Leisure World Cohort Study, collected about 20 years earlier. A total of 559 participants without dementia were followed every 6 months for up to 10 years. Results A total of 224 participants developed dementia during follow-up (mean = 2.8 years). Compared with those without hypertension, participants whose hypertension onset age was 80 to 89 years had a lower dementia risk (hazard ratio = 0.58, P = .04) and participants with an onset age of 90+ years had the lowest risk (hazard ratio = 0.37, P = .004). Discussion Developing hypertension at older ages may protect against dementia. Understanding the mechanisms for this lower risk is important for determining ways to prevent dementia in the very elderly. [ABSTRACT FROM AUTHOR]