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BackgroundSocial support may be a modifiable risk factor for cognitive impairment. However, few long-term, large prospective studies have examined associations of various forms of social support with incident mild cognitive impairment (MCI) and dementia.ObjectiveTo examine associations of perceived social support with incident MCI and dementia among community-dwelling older women.MethodsThis prospective cohort study included 6,670 women from the Women's Health Initiative Memory Study who were cognitively unimpaired at enrollment. We used Cox proportional hazards models to assess associations between perceived social support with incident MCI, dementia, or either MCI/dementia during an average 10.7 (SD = 6.1)-year follow-up. Modelling was repeated for emotional/information support, affection support, tangible support, and positive social interaction subscales of social support.ResultsAmong 6,670 women (average age = 70 years [SD = 3.8]; 97.0% non-Hispanic/Latina; 89.8% White), greater perceived social support was associated with lower risk of MCI/dementia after adjustment for age, ethnicity, race, hormone therapy, education, income, diabetes, hypertension, and body mass index (Tertile [T]3 versus T1: HR = 0.85, 95% CI 0.74-0.99; ptrend = 0.08). Associations were significant for emotional/information support (T3 versus T1: HR = 0.84, 95% CI 0.72-0.97; ptrend = 0.04) and positive social interaction (T3 versus T1: HR = 0.85, 95% CI 0.73-0.99; ptrend = 0.06) subscales. Associations were attenuated and not significant after adjustment for depressive symptom severity.ObjectivePerceived social support, emotional/information support, and positive social interaction were associated with incident MCI/dementia among older women. Results were not significant after adjustment for depressive symptom severity. Improving social support may reduce risk of MCI and dementia in older women.

BACKGROUND: Depressive symptoms are associated with age-related cognitive impairment, but the relative risk of specific subtypes of mild cognitive impairment (MCI) conferred by depressive symptoms is unclear. The purpose of this exploratory study was to determine the longitudinal association between baseline depressive symptoms and incident cases of MCI subtypes (amnestic vs. non-amnestic) and probable dementia (PD) (Alzheimers disease, vascular, mixed) among postmenopausal women. METHODS: Depressive symptoms were assessed at study baseline using an 8-item Burnam algorithm in 7043 postmenopausal women who participated in the Womens Health Initiative Memory Study (WHIMS) and the WHIMS-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO) extension study. During the median 9.4-year follow-up interval, the presence of MCI and PD was classified by a central adjudication committee. Classification of participants by MCI subtype (amnestic single and multi-domain, non-amnestic single and multi-domain) was done algorithmically based on established criteria using data from annual cognitive testing. RESULTS: At baseline, 557 women (7.9%) had clinically significant depressive symptoms based on Burnam algorithm cut-point of 0.06. Depressive symptoms at baseline were associated with an increased risk of incident amnestic MCI (hazard ratio [HR] = 1.91, 95% confidence interval [CI] 1.32-2.78, p

BackgroundGuidelines recommend measuring blood pressure (BP) in both arms, adopting the higher arm readings for diagnosis and management. Data to support this recommendation are lacking. We evaluated associations of higher and lower arm systolic BPs with diagnostic and treatment thresholds, and prognosis in hypertension, using data from the Inter-arm Blood Pressure Difference-Individual Participant Data Collaboration.MethodsOne-stage multivariable Cox regression models, stratified by study, were used to examine associations of higher or lower reading arm BPs with cardiovascular mortality, all-cause mortality, and cardiovascular events, in individual participant data meta-analyses pooled from 23 cohorts. Cardiovascular events were modelled for Framingham and atherosclerotic cardiovascular disease risk scores. Model fit was compared throughout using Akaike information criteria. Proportions reclassified across guideline recommended intervention thresholds were also compared.ResultsWe analyzed 53 172 participants: mean age 60 years; 48% female. Higher arm BP, compared with lower arm, reclassified 12% of participants at either 130 or 140 mm Hg systolic BP thresholds (both P

BackgroundEpigenetic age acceleration (AgeAccel), which indicates faster biological aging relative to chronological age, has been associated with lower cognitive function. However, the association of AgeAccel with mild cognitive impairment (MCI) or dementia is not well-understood. We examined associations of 4 AgeAccel measures with incident MCI and dementia.MethodsThis prospective analysis included 578 older women from the Women's Health Initiative Memory Study selected for a case-cohort study of coronary heart disease (CHD). Women were free of CHD and cognitive impairment at baseline. Associations of AgeAccel measures (intrinsic AgeAccel [IEAA], extrinsic AgeAccel [EEAA], AgeAccelPheno, and AgeAccelGrim) with risks for incident adjudicated diagnoses of MCI and dementia overall and stratified by incident CHD status were evaluated.ResultsIEAA was not significantly associated with MCI (HR, 1.23; 95% CI, 0.99-1.53), dementia (HR, 1.10; 95% CI, 0.88-1.38), or cognitive impairment (HR, 1.18; 95% CI, 0.99-1.40). In stratified analysis by incident CHD status, there was a 39% (HR, 1.39; 95% CI, 1.07-1.81) significantly higher risk of MCI for every 5-year increase in IEAA among women who developed CHD during follow-up. Other AgeAccel measures were not significantly associated with MCI or dementia.ConclusionsIEAA was not significantly associated with cognitive impairment overall but was associated with impairment among women who developed CHD. Larger studies designed to examine associations of AgeAccel with cognitive impairment are needed, including exploration of whether associations are stronger in the setting of underlying vascular pathologies.

Exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) have been associated with the emergence of depressive symptoms in older adulthood, although most studies used cross-sectional outcome measures. Elucidating the brain structures mediating the adverse effects can strengthen the causal role between air pollution and increasing depressive symptoms. We evaluated whether smaller volumes of brain structures implicated in late-life depression mediate associations between ambient air pollution exposure and changes in depressive symptoms. This prospective study included 764 community-dwelling older women (aged 81.6 ± 3.6 in 2008-2010) from the Women's Health Initiative Memory Study (WHIMS) Magnetic Resonance Imaging study (WHIMS-MRI; 2005-06) and WHIMS-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO; 2008-16). Three-year average annual mean concentrations (scaled by interquartile range [IQR]) of ambient PM2.5 (in μg/m3; IQR = 3.14 μg/m3) and NO2 (in ppb; IQR = 7.80 ppb) before WHIMS-MRI were estimated at participants' addresses via spatiotemporal models. Mediators included structural brain MRI-derived grey matter volumes of the prefrontal cortex and structures of the limbic-cortical-striatal-pallidal-thalamic circuit. Depressive symptoms were assessed annually by the 15-item Geriatric Depression Scale. Structural equation models were constructed to estimate associations between exposure, structural brain volumes, and depressive symptoms. Increased exposures (by each IQR) were associated with greater annual increases in depressive symptoms (βPM2.5 = 0.022; 95% Confidence Interval (CI) = 0.003, 0.042; βNO2 = 0.019; 95% CI = 0.001, 0.037). The smaller volume of prefrontal cortex associated with exposures partially mediated the associations of increased depressive symptoms with NO2 (8%) and PM2.5 (13%), and smaller insula volume associated with NO2 contributed modestly (13%) to the subsequent increase in depressive symptoms. We demonstrate the first evidence that the smaller volumes of the prefrontal cortex and insula may mediate the subsequent increases in depressive symptoms associated with late-life exposures to NO2 and PM2.5.

BackgroundWhether racial/ethnic disparities in Alzheimer's disease (AD) risk may be explained by ambient fine particles (PM2.5) has not been studied.MethodWe conducted a prospective, population-based study on a cohort of Black (n = 481) and White (n = 6 004) older women (aged 65-79) without dementia at enrollment (1995-1998). Cox models accounting for competing risk were used to estimate the hazard ratio (HR) for racial/ethnic disparities in AD (1996-2010) defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edition and the association with time-varying annual average PM2.5 (1999-2010) estimated by spatiotemporal model.ResultsOver an average follow-up of 8.3 (±3.5) years with 158 incident cases (21 in Black women), the racial disparities in AD risk (range of adjusted HRBlack women = 1.85-2.41) observed in various models could not be explained by geographic region, age, socioeconomic characteristics, lifestyle factors, cardiovascular risk factors, and hormone therapy assignment. Estimated PM2.5 exposure was higher in Black (14.38 ± 2.21 µg/m3) than in White (12.55 ± 2.76 µg/m3) women, and further adjustment for the association between PM2.5 and AD (adjusted HRPM2.5 = 1.18-1.28) slightly reduced the racial disparities by 2%-6% (HRBlack women = 1.81-2.26). The observed association between PM2.5 and AD risk was ~2 times greater in Black (HRPM2.5 = 2.10-2.60) than in White (HRPM2.5 = 1.07-1.15) women (range of interaction ps:

OBJECTIVE: To examine the association of sleep disturbance with Parkinson disease (PD) during 10+ years of follow-up among postmenopausal women, 50 to 79 years of age at baseline. METHODS: Longitudinal data on 130,502 study-eligible women (mean ± standard deviation baseline age = 63.16 ± 7.20 y) from the Womens Health Initiative Clinical Trials and Womens Health Initiative Observational Study were analyzed. The cohort was followed for 15.88 ± 6.50 years, yielding 2,829 (2.17%) PD cases. Sleep disturbance (habitual sleep duration, insomnia symptoms, obstructive sleep apnea risk factors, sleep aids among those with WHI Insomnia Rating Scale scores (WHIIRS) > 9) was measured at baseline and one follow-up time by September 12, 2005. Cox proportional hazards models evaluated relationships controlling for sociodemographic, lifestyle, and health characteristics. RESULTS: PD was significantly associated with long sleep duration (≥9 h) versus a benchmark of 7 to 8 hours (hazard ratio [HR] = 1.296, 95% confidence interval [CI]: 1.153-1.456), WHIIRS (>9 vs ≤9) (HR = 1.114, 95% CI:1.023-1.214), and use of sleep aids (yes vs no) (HR = 1.332, 95% CI:1.153-1.539) among those with WHIIRS > 9. Compared with 7 to 8 hours, short (

BACKGROUND: Cardiometabolic disorders (hypertension, diabetes) are key modifiable risk factors for Alzheimers disease and related disorders. They often co-occur; yet, the extent to which they independently affect brain structure and function is unclear. OBJECTIVE: We hypothesized their combined effect is greater in associations with cognitive function and neuroimaging biomarkers of white matter (WM) health and cerebral perfusion in a diverse older adult cohort. METHODS: Participants aged 50-85 years received: clinical evaluation, oral glucose tolerance testing, neuroimaging, cognitive testing, and adjudication. Neuroimaging included: T1 (gray [GM]/WM segmentation, regional volumes/thicknesses); FLAIR (WM hyperintensity volume [WMHv]; arterial spin labeling (cerebral blood flow); diffusion tensor imaging (fractional anisotropy [FA]); and neurite orientation dispersion and density imaging (Free Water). Hypertension (HTN) and impaired glucose tolerance (IGT) were staged and cardiometabolic status was categorized (HTN only, IGT only, IGT+HTN, neither). Multivariable linear regression modeled associations with cognitive and neuroimaging measures (covariates: age, gender, race). RESULTS: MRI was available for 478 participants (35% mild cognitive impairment, 10% dementia) with mean age 70±8 years, 74% with HTN, 61% with IGT, and 15% self-identified as Black/African-American. IGT+HTN was significantly associated with cognitive impairment, higher WM Free Water and WMHv, lower FA, and lower GM perfusion compared to neither factor. HTN alone was associated with poorer cognition and lower GM perfusion. Cardiometabolic factors were not associated with GM macrostructure (volumes, temporal lobe cortical thickness) or cognitive status. CONCLUSION: HTN and its co-occurrence with IGT (HTN+IGT) were associated with lower global cognitive performance and reduced GM perfusion and impaired WM microstructure.

PurposeTo investigate if accounting for a cup-to-disc ratio (CDR) genetic risk score (GRS) modified the association between large CDR and cognitive function among women.DesignThis was a retrospective study using data from the Women's Health Initiative.MethodsPatients with glaucoma or ocular hypertension were excluded. Large CDR was defined as ≥ 0.6 in either eye. Cognitive function was measured by the Modified Mini-Mental State Examination (3MSE). We used the combined effects from 13 single nucleotide polymorphisms (SNPs) to formulate the GRS for CDR. We used logistic regression to investigate associations between weighted GRS and large CDR, then a linear regression to assess the association between weighted GRS and 3MSE scores, and between weighted GRS, CDR, and 3MSE scores, adjusted for demographic and clinical characteristics.ResultsFinal analyses included 1,196 White women with mean age of 69.60 ± 3.62 years and 7.27% with large CDR. Mean GRS in women with and without large CDR was 1.51 ± 0.31 vs. 1.41 ± 0.36, respectively (p = 0.004). The odds of large CDR for a one unit increase in GRS was 2.30 (95% CI: (1.22, 4.36), p = 0.011). Adding the CDR GRS in the model with CDR and 3MSE, women with large CDR still had statistically significantly lower 3MSE scores than those without large CDR, yielding a predicted mean difference in 3MSE scores of 0.84 (p = 0.007).ConclusionsIndependent of the CDR GRS, women with large CDR had a lower cognitive function.

Introduction Social jetlag (SJL), the discrepancy in sleep timing between weekdays and weekends, is associated with higher BMI and cardiometabolic risk and is common in young adults. We examined whether chronic SJL impacts weight gain in young adults participating in a weight gain prevention trial. Methods Young adults (n = 599, age 18-35; BMI: 21.0-30.9 kg/m.sup.2) completed assessments at 0, 4, 12, and 24 months. Multilevel mixed growth models were used to examine (1) associations between demographics and longitudinal SJL and (2) longitudinal SJL as a predictor of weight change and cardiometabolic outcomes. SJL was assessed as a continuous and clinically-significant dichotomous (< vs. [greater than or equal to]2 h) variable. Results 38% of participants had clinically-significant SJL at [greater than or equal to] 1 timepoints (Baseline M ± SD = 1.3±0.89). Younger (b=-0.05, p < 0.001), female (b = 0.18, p = 0.037) and Black (compared to White, b = 0.23, p = 0.045) participants were more likely to have greater SJL. Individuals with high SJL ([greater than or equal to] 2 h; between-person effect) were more likely to have greater weight gain over 2 years (b = 0.05, p = 0.028). High SJL did not affect the rate of change in waist circumference or cardiometabolic markers over time. Conclusions High SJL is associated with greater weight gain over time. Reducing SJL may positively impact weight status in young adults., Author(s): Jacqueline F. Hayes [sup.1] [sup.8] , Leah M. Schumacher [sup.1] [sup.8] , Autumn Lanoye [sup.4] [sup.5] , Jessica Gokee LaRose [sup.4] , Deborah F. Tate [sup.2] , Mark A. [...]

Background: Type 2 diabetes mellitus and overweight/obesity increase healthcare costs. Both are also associated with accelerated aging. However, the contributions of this accelerated aging to increased healthcare costs are unknown. Methods: We use data from a 8‐year longitudinal cohort followed at 16 U.S. clinical research sites. Participants were adults aged 45–76 years with established type 2 diabetes and overweight or obesity who had enrolled in the Action for Health in Diabetes clinical trial. They were randomly (1:1) assigned to either an intensive lifestyle intervention focused on weight loss versus a comparator of diabetes support and education. A validated deficit accumulation frailty index (FI) was used to characterize biological aging. Discounted annual healthcare costs were estimated using national databases in 2012 dollars. Descriptive characteristics were collected by trained and certified staff. Results: Compared with participants in the lowest tertile (least frail) of baseline FI, those in the highest tertile (most frail) at Year 1 averaged $714 (42%) higher medication costs, $244 (22%) higher outpatient costs, and $800 (134%) higher hospitalization costs (p < 0.001). At Years 4 and 8, relatively greater increases in FI (third vs. first tertile) were associated with an approximate doubling of total healthcare costs (p < 0.001). Mean (95% confidence interval) relative annual savings in healthcare costs associated with randomization to the intensive lifestyle intervention were $437 ($195, $579) per year during Years 1–4 and $461 ($232, $690) per year during Years 1–8. These were attenuated and the 95% confidence interval no longer excluded $0 after adjustment for the annual FI differences from baseline. Conclusions: Deficit accumulation frailty tracks well with healthcare costs among adults with type 2 diabetes and overweight or obesity. It may serve as a useful marker to project healthcare needs and as an intermediate outcome in clinical trials. [ABSTRACT FROM AUTHOR]

Objective Assess the feasibility and concurrent validity of a modified Uniform Data Set version 3 (UDSv3) for remote administration for individuals with normal cognition (NC), mild cognitive impairment (MCI), and early dementia. Method Participants (N =  93) (age: 72.8 [8.9] years; education: 15.6 [2.5] years; 72% female; 84% White) were enrolled from the Wake Forest ADRC. Portions of the UDSv3 cognitive battery, plus the Rey Auditory Verbal Learning Test, were completed by telephone or video within ~6 months of participant's in-person visit. Adaptations for phone administration (e.g. Oral Trails for Trail Making Test [TMT] and Blind Montreal Cognitive Assessment [MoCA] for MoCA) were made. Participants reported on the pleasantness, difficulty, and preference for each modality. Staff provided validity ratings for assessments. Participants' remote data were adjudicated by cognitive experts blinded to the in person-diagnosis (NC [ N =  44], MCI [ N =  35], Dementia [ N =  11], or other [ N =  3]). Results Remote assessments were rated as pleasant as in-person assessments by 74% of participants and equally difficult by 75%. Staff validity rating (video = 92%; phone = 87.5%) was good. Concordance between remote/in-person scores was generally moderate to good (r  = .3 −.8; p  < .05) except for TMT-A/OTMT-A (r  = .3; p  > .05). Agreement between remote/in-person adjudicated cognitive status was good (k  = .61–.64). Conclusions We found preliminary evidence that older adults, including those with cognitive impairment, can be assessed remotely using a modified UDSv3 research battery. Adjudication of cognitive status that relies on remotely collected data is comparable to classifications using in-person assessments. [ABSTRACT FROM AUTHOR]

Many head acceleration events (HAEs) observed in youth football emanate from a practice environment. This study aimed to evaluate HAEs in youth football practice drills using a mouthpiece-based sensor, differentiating between inertial and direct HAEs. Head acceleration data were collected from athletes participating on 2 youth football teams (ages 11–13 y) using an instrumented mouthpiece-based sensor during all practice sessions in a single season. Video was recorded and analyzed to verify and assign HAEs to specific practice drill characteristics, including drill intensity, drill classification, and drill type. HAEs were quantified in terms of HAEs per athlete per minute and peak linear and rotational acceleration and rotational velocity. Mixed-effects models were used to evaluate the differences in kinematics, and generalized linear models were used to assess differences in HAE frequency between drill categories. A total of 3237 HAEs were verified and evaluated from 29 football athletes enrolled in this study. Head kinematics varied significantly between drill categorizations. HAEs collected at higher intensities resulted in significantly greater kinematics than lower-intensity drills. The results of this study add to the growing body of evidence informing evidence-based strategies to reduce head impact exposure and concussion risk in youth football practices. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Apolipoprotein E4 (APOE4) carriers' tendency toward hypercholesterolemia may contribute to Alzheimer's disease (AD) risk through oxysterols, which traverse the blood‐brain barrier. METHODS: Relationships between baseline plasma oxysterols, APOE status, serum lipids, and cognitive impairment risk were examined in 328 postmenopausal women from the Women's Health Initiative Memory Study. Women were followed for 25 years or until incident dementia or cognitive impairment. RESULTS: Levels of 24(S)‐hydroxycholesterol (24‐OHC), 27‐hydroxycholesterol (27‐OHC), and 24‐OHC/27‐OHC ratio did not differ by APOE status (p's > 0.05). Higher 24‐OHC and 27‐OHC were associated with higher total, low density lipoprotein (LDL), non‐high density lipoprotein (HDL), remnant, LDL/HDL, and total/HDL cholesterol and triglycerides (p's < 0.05). Higher 24‐OHC/27‐OHC was associated with greater dementia risk (hazard ratio = 1.51, 95% confidence interval:1.02‐2.22), which interaction analyses revealed as significant for APOE3 and APOE4+, but not APOE2+ carriers. DISCUSSION: Less favorable lipid profiles were associated with higher oxysterol levels. A higher ratio of 24‐OHC/27‐OHC may contribute to dementia risk in APOE3 and APOE4+ carriers. [ABSTRACT FROM AUTHOR]