Association of improved air quality with lower dementia risk in older women.

Late-life ambient air pollution is a risk factor for brain aging, but it remains unknown if improved air quality (AQ) lowers dementia risk. We studied a geographically diverse cohort of older women dementia free at baseline in 2008 to 2012 (n = 2,239, aged 74 to 92). Incident dementia was centrally adjudicated annually. Yearly mean concentrations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were estimated using regionalized national universal kriging models and averaged over the 3-y period before baseline (recent exposure) and 10 y earlier (remote exposure). Reduction from remote to recent exposures was used as the indicator of improved AQ. Cox proportional hazard ratios (HRs) for dementia risk associated with AQ measures were estimated, adjusting for sociodemographic, lifestyle, and clinical characteristics. We identified 398 dementia cases during follow up (median = 6.1 y). PM2.5 and NO2 reduced significantly over the 10 y before baseline. Larger AQ improvement was associated with reduced dementia risks (HRPM2.5 0.80 per 1.78 µg/m3, 95% CI 0.71-0.91; HRNO2 0.80 per 3.91 parts per billion, 95% CI 0.71-0.90), equivalent to the lower risk observed in women 2.4 y younger at baseline. Higher PM2.5 at baseline was associated with higher dementia risk (HRPM2.5 1.16 per 2.90 µg/m3, 95% CI 0.98-1.38), but the lower dementia risk associated with improved AQ remained after further adjusting for recent exposure. The observed associations did not substantially differ by age, education, geographic region, Apolipoprotein E e4 genotypes, or cardiovascular risk factors. Long-term AQ improvement in late life was associated with lower dementia risk in older women.

Physical Rehabilitation for Older Patients Hospitalized for Heart Failure.

BACKGROUND: Older patients who are hospitalized for acute decompensated heart failure have high rates of physical frailty, poor quality of life, delayed recovery, and frequent rehospitalizations. Interventions to address physical frailty in this population are not well established. METHODS: We conducted a multicenter, randomized, controlled trial to evaluate a transitional, tailored, progressive rehabilitation intervention that included four physical-function domains (strength, balance, mobility, and endurance). The intervention was initiated during, or early after, hospitalization for heart failure and was continued after discharge for 36 outpatient sessions. The primary outcome was the score on the Short Physical Performance Battery (total scores range from 0 to 12, with lower scores indicating more severe physical dysfunction) at 3 months. The secondary outcome was the 6-month rate of rehospitalization for any cause. RESULTS: A total of 349 patients underwent randomization; 175 were assigned to the rehabilitation intervention and 174 to usual care (control). At baseline, patients in each group had markedly impaired physical function, and 97% were frail or prefrail; the mean number of coexisting conditions was five in each group. Patient retention in the intervention group was 82%, and adherence to the intervention sessions was 67%. After adjustment for baseline Short Physical Performance Battery score and other baseline characteristics, the least-squares mean (±SE) score on the Short Physical Performance Battery at 3 months was 8.3±0.2 in the intervention group and 6.9±0.2 in the control group (mean between-group difference, 1.5; 95% confidence interval [CI], 0.9 to 2.0; P<0.001). At 6 months, the rates of rehospitalization for any cause were 1.18 in the intervention group and 1.28 in the control group (rate ratio, 0.93; 95% CI, 0.66 to 1.19). There were 21 deaths (15 from cardiovascular causes) in the intervention group and 16 deaths (8 from cardiovascular causes) in the control group. The rates of death from any cause were 0.13 and 0.10, respectively (rate ratio, 1.17; 95% CI, 0.61 to 2.27). CONCLUSIONS: In a diverse population of older patients who were hospitalized for acute decompensated heart failure, an early, transitional, tailored, progressive rehabilitation intervention that included multiple physical-function domains resulted in greater improvement in physical function than usual care. (Funded by the National Institutes of Health and others; REHAB-HF ClinicalTrials.gov number, NCT02196038.).

Intensive lifestyle intervention in type 2 diabetes and risk of incident coronary artery disease for the common haptoglobin phenotypes: the Look AHEAD study.

BACKGROUND: Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Disease Risk in Diabetes (ACCORD) participants with the haptoglobin (Hp) 2-2 phenotype only. It remains unknown whether Hp phenotype modifies the effect of an intensive lifestyle intervention (ILI) on CAD in type 2 diabetes. METHODS: Haptoglobin phenotype was measured in 4542 samples from the Action for Health in Diabetes (Look AHEAD) study. Cox regression models assessed the effect of ILI (focused on weight loss from caloric restriction and physical activity) versus diabetes support and education (DSE) on CAD events in each phenotype group, and within pre-specified subgroups including race/ethnicity, sex, history of cardiovascular disease, diabetes medication use, and diabetes duration. RESULTS: 1590 (35%) participants had the Hp2-2 phenotype. The ILI did not lower glycated hemoglobin (%HbA1c) to < 6.5% in either phenotype, with a peak significant difference between treatment arms of 0.5% [non-Hp2-2] and 0.6% [Hp2-2]. The cumulative CAD incidence was 13.4% and 13.8% in the DSE arm and 12.2% and 13.6% in the ILI arm for non-Hp2-2 and Hp2-2 groups, respectively. Compared to DSE, the ILI was not associated with CAD among participants without (HR = 0.95, 95% CI 0.78-1.17) or with (0.89, 0.68-1.19) the Hp2-2 phenotype (p-interaction between Hp phenotype and ILI = 0.58). After Bonferroni correction, there were no significant results among any subgroups. CONCLUSIONS: Hp phenotype did not modify the effect of the weight loss ILI on risk of CAD in Look AHEAD, potentially because it did not substantially impact glycemic control among participants with or without the Hp2-2 phenotype. Further research is needed to determine if these results are conclusive.

Plasma oxysterols are associated with serum lipids and dementia risk in older women.

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.

20-year depressive symptoms, dementia, and structural neuropathology in older women.

INTRODUCTION: The course of depressive symptoms and dementia risk is unclear, as are potential structural neuropathological common causes. METHODS: Utilizing joint latent class mixture models, we identified longitudinal trajectories of annually assessed depressive symptoms and dementia risk over 21 years in 957 older women (baseline age 72.7 years old) from the Women's Health Initiative Memory Study. In a subsample of 569 women who underwent structural magnetic resonance imaging, we examined whether estimates of cerebrovascular disease and Alzheimer's disease (AD)-related neurodegeneration were associated with identified trajectories. RESULTS: Five trajectories of depressive symptoms and dementia risk were identified. Compared to women with minimal symptoms, women who reported mild and stable and emerging depressive symptoms were at the highest risk of developing dementia and had more cerebrovascular disease and AD-related neurodegeneration. DISCUSSION: There are heterogeneous profiles of depressive symptoms and dementia risk. Common neuropathological factors may contribute to both depression and dementia. Highlights The progression of depressive symptoms and concurrent dementia risk is heterogeneous. Emerging depressive symptoms may be a prodromal symptom of dementia. Cerebrovascular disease and AD are potentially shared neuropathological factors.

Study design and methods: U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER).

INTRODUCTION: The U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) is conducted to confirm and expand the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in Americans. METHODS: U.S. POINTER was planned as a 2-year randomized controlled trial of two lifestyle interventions in 2000 older adults at risk for dementia due to well-established factors. The primary outcome is a global cognition composite that permits harmonization with FINGER. RESULTS: U.S. POINTER is centrally coordinated and conducted at five clinical sites (ClinicalTrials.gov: NCT03688126). Outcomes assessments are completed at baseline and every 6 months. Both interventions focus on exercise, diet, cognitive/social stimulation, and cardiovascular health, but differ in intensity and accountability. The study partners with a worldwide network of similar trials for harmonization of methods and data sharing. DISCUSSION: U.S. POINTER is testing a potentially sustainable intervention to support brain health and Alzheimer's prevention for Americans. Impact is strengthened by the targeted participant diversity and expanded scientific scope through ancillary studies.

Incident and recurrent hypoglycaemia with linagliptin and glimepiride over a median of 6 years in the CAROLINA cardiovascular outcome trial.

AIM: The CAROLINA trial established non-inferiority of linagliptin versus glimepiride for major adverse cardiovascular events in patients with relatively early type 2 diabetes at increased cardiovascular risk. In pre-specified and post-hoc analyses, we investigated treatment effects on total hypoglycaemic burden in CAROLINA. MATERIALS AND METHODS: Patients were randomized and treated with 5 mg linagliptin (n = 3014) or 1-4 mg glimepiride (n = 3000) once daily added to standard care. Hypoglycaemia captured from investigator-reported adverse events was analysed with Poisson and negative binomial regressions for the first and total (first plus recurrent) events, respectively. The influence of insulin initiation and glycated haemoglobin (HbA1c) change on the treatment effect for hypoglycaemia was also explored. RESULTS: Over 6.3 years median follow-up, average HbA1c over time did not differ between linagliptin versus glimepiride (weighted mean difference [95% confidence interval]: 0.00%, [-0.05, 0.05]), nor did insulin initiation (18.6% vs. 19.2% of patients, respectively), whereas body weight was lower with linagliptin (-1.54 kg, [-1.80, -1.28]). Hypoglycaemia frequency was lower with linagliptin across all hypoglycaemia categories, including severe episodes. Rate ratios (95% confidence interval) for first and total events for investigator-reported hypoglycaemia were 0.21 (0.19-0.24) and 0.12 (0.10-0.14), respectively, with 8.7 first and 60.8 total estimated events prevented/100 patient-years with linagliptin versus glimepiride. These differences occurred during night-time and daytime, and in subgroup analyses of total events. Treatment differences in hypoglycaemia were neither impacted by HbA1c changes nor insulin initiation. CONCLUSIONS: Across the severity spectrum, linagliptin substantially reduced the hypoglycaemic burden versus glimepiride in patients with relatively early type 2 diabetes at increased cardiovascular risk.

Effects of cocoa extract and a multivitamin on cognitive function: A randomized clinical trial.

INTRODUCTION: Dietary supplements are touted for cognitive protection, but supporting evidence is mixed. COSMOS-Mind tested whether daily administration of cocoa extract (containing 500 mg/day flavanols) versus placebo and a commercial multivitamin-mineral (MVM) versus placebo improved cognition in older women and men. METHODS: COSMOS-Mind, a large randomized two-by-two factorial 3-year trial, assessed cognition by telephone at baseline and annually. The primary outcome was a global cognition composite formed from mean standardized (z) scores (relative to baseline) from individual tests, including the Telephone Interview of Cognitive Status, Word List and Story Recall, Oral Trail-Making, Verbal Fluency, Number Span, and Digit Ordering. Using intention-to-treat, the primary endpoint was change in this composite with 3 years of cocoa extract use. The pre-specified secondary endpoint was change in the composite with 3 years of MVM supplementation. Treatment effects were also examined for executive function and memory composite scores, and in pre-specified subgroups at higher risk for cognitive decline. RESULTS: A total of 2262 participants were enrolled (mean age = 73y; 60% women; 89% non-Hispanic White), and 92% completed the baseline and at least one annual assessment. Cocoa extract had no effect on global cognition (mean z-score = 0.03, 95% CI: -0.02 to 0.08; P = .28). Daily MVM supplementation, relative to placebo, resulted in a statistically significant benefit on global cognition (mean z = 0.07, 95% CI 0.02 to 0.12; P = .007), and this effect was most pronounced in participants with a history of cardiovascular disease (no history: 0.06, 95% CI 0.01 to 0.11; history: 0.14, 95% CI -0.02 to 0.31; interaction, nominal P = .01). Multivitamin-mineral benefits were also observed for memory and executive function. The cocoa extract by MVM group interaction was not significant for any of the cognitive composites. DISCUSSION: Cocoa extract did not benefit cognition. However, COSMOS-Mind provides the first evidence from a large, long-term, pragmatic trial to support the potential efficacy of a MVM to improve cognition in older adults. Additional work is needed to confirm these findings in a more diverse cohort and to identify mechanisms to account for MVM effects. HIGHLIGHTS: COSMOS-Mind was a large simple pragmatic randomized clinical trial in older adults conducted by mail and telephone. The trial used a two-by-two factorial design to assess treatment effects of two different interventions within a single large study. We found no cognitive benefit of daily cocoa extract administration (containing 500 mg flavanols) for 3 years. Daily multivitamin-mineral (MVM) supplementation for 3 years improved global cognition, episodic memory, and executive function in older adults. The MVM benefit appeared to be greater for adults with cardiovascular disease.

Impact of multivitamin-mineral and cocoa extract on incidence of mild cognitive impairment and dementia: Results from the COcoa Supplement and Multivitamin Outcomes Study for the Mind (COSMOS-Mind).

INTRODUCTION: We assessed the effects of multivitamin-mineral and cocoa extract supplementation on incident mild cognitive impairment (MCI) and all-cause probable dementia. METHODS: COSMOS-Mind (N = 2262), a 2 × 2 factorial, randomized-controlled clinical trial administered a telephone-based cognitive battery at baseline and annually for 3 years. Incidence rates of MCI, and separately dementia, were compared among treatment arms with proportional hazards regression. RESULTS: Over 3 years, 110 incident MCI and 14 incident dementia cases were adjudicated. Incidence rates did not vary by assignment to multivitamin-mineral or cocoa extract (all p's ≥ 0.05); however, statistical power was low. When participants assigned to multivitamin-mineral versus placebo converted to MCI, their scores for global cognition (p = 0.03) and executive function (p < 0.001) were higher and had declined less relative to the previous year (p = 0.03 for global cognition; p = 0.004 for executive function). DISCUSSION: Multivitamin-mineral therapy may provide cognitive resilience, countering conversion to MCI, but not significantly reduce its incidence over 3 years. HIGHLIGHTS: Multivitamin-mineral supplementation did not reduce risks for cognitive impairment. Cocoa extract supplementation did not reduce risks for cognitive impairment. Multivitamin-mineral supplementation slowed cognitive declines for incident mild cognitive impairment.

Associations of dietary cholesterol and fat, blood lipids, and risk for dementia in older women vary by APOE genotype.

INTRODUCTION: Whether apolipoprotein E's (APOE's) involvement in lipid metabolism contributes to Alzheimer's disease (AD) risk remains unknown. METHODS: Incident probable dementia and cognitive impairment (probable dementia+mild cognitive impairment) were analyzed in relation to baseline serum lipids (total, low-density lipoprotein [LDL], high-density lipoprotein [HDL], non-HDL cholesterol, total-to-HDL, LDL-to-HDL, remnant cholesterol, and triglycerides) using Mendelian randomization in 5358 postmenopausal women from the Women's Health Initiative Memory Study. We also examined associations of baseline dietary cholesterol and fat with lipids based on APOE status. RESULTS: After an average of 11.13 years, less favorable lipid levels related to greater dementia and cognitive impairment risk. Dementia (odds ratio [OR] = 3.13; 95% confidence interval [CI]: 2.31 to 4.24) and cognitive impairment (OR = 2.38; 95% CI: 1.85 to 3.06) risk were greatest in relation to higher remnant cholesterol levels. Greater cholesterol consumption related to poorer lipids in APOE4+ compared to APOE3 carriers. DISCUSSION: APOE4+ carriers consuming more cholesterol had less favorable lipids, which were associated with greater dementia and cognitive impairment risk. HIGHLIGHTS: Less favorable serum lipids were associated with higher dementia incidence. Mendelian randomization findings suggest causality between lipids and dementia. Lipid levels in older women may be clinical indicators of dementia risk. APOE4 carriers had poorest lipid profiles in relation to cholesterol consumption. APOE risk for dementia may be modifiable through lipid management.

Characterization of Head Acceleration Exposure During Youth Football Practice Drills.

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.

Air quality improvement and cognitive decline in community-dwelling older women in the United States: A longitudinal cohort study.

BACKGROUND: Late-life exposure to ambient air pollution is a modifiable risk factor for dementia, but epidemiological studies have shown inconsistent evidence for cognitive decline. Air quality (AQ) improvement has been associated with improved cardiopulmonary health and decreased mortality, but to the best of our knowledge, no studies have examined the association with cognitive function. We examined whether AQ improvement was associated with slower rate of cognitive decline in older women aged 74 to 92 years. METHODS AND FINDINGS: We studied a cohort of 2,232 women residing in the 48 contiguous US states that were recruited from more than 40 study sites located in 24 states and Washington, DC from the Women's Health Initiative (WHI) Memory Study (WHIMS)-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO) study. They were predominantly non-Hispanic White women and were dementia free at baseline in 2008 to 2012. Measures of annual (2008 to 2018) cognitive function included the modified Telephone Interview for Cognitive Status (TICSm) and the telephone-based California Verbal Learning Test (CVLT). We used regionalized universal kriging models to estimate annual concentrations (1996 to 2012) of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) at residential locations. Estimates were aggregated to the 3-year average immediately preceding (recent exposure) and 10 years prior to (remote exposure) WHIMS-ECHO enrollment. Individual-level improved AQ was calculated as the reduction from remote to recent exposures. Linear mixed effect models were used to examine the associations between improved AQ and the rates of cognitive declines in TICSm and CVLT trajectories, adjusting for sociodemographic (age; geographic region; race/ethnicity; education; income; and employment), lifestyle (physical activity; smoking; and alcohol), and clinical characteristics (prior hormone use; hormone therapy assignment; depression; cardiovascular disease (CVD); hypercholesterolemia; hypertension; diabetes; and body mass index [BMI]). For both PM2.5 and NO2, AQ improved significantly over the 10 years before WHIMS-ECHO enrollment. During a median of 6.2 (interquartile range [IQR] = 5.0) years of follow-up, declines in both general cognitive status (ß = -0.42/year, 95% CI: -0.44, -0.40) and episodic memory (ß = -0.59/year, 95% CI: -0.64, -0.54) were observed. Greater AQ improvement was associated with slower decline in TICSm (ßPM2.5improvement = 0.026 per year for improved PM2.5 by each IQR = 1.79 µg/m3 reduction, 95% CI: 0.001, 0.05; ßNO2improvement = 0.034 per year for improved NO2 by each IQR = 3.92 parts per billion [ppb] reduction, 95% CI: 0.01, 0.06) and CVLT (ßPM2.5 improvement = 0.070 per year for improved PM2.5 by each IQR = 1.79 µg/m3 reduction, 95% CI: 0.02, 0.12; ßNO2improvement = 0.060 per year for improved NO2 by each IQR = 3.97 ppb reduction, 95% CI: 0.005, 0.12) after adjusting for covariates. The respective associations with TICSm and CVLT were equivalent to the slower decline rate found with 0.9 to 1.2 and1.4 to 1.6 years of younger age and did not significantly differ by age, region, education, Apolipoprotein E (ApoE) e4 genotypes, or cardiovascular risk factors. The main limitations of this study include measurement error in exposure estimates, potential unmeasured confounding, and limited generalizability. CONCLUSIONS: In this study, we found that greater improvement in long-term AQ in late life was associated with slower cognitive declines in older women. This novel observation strengthens the epidemiologic evidence of an association between air pollution and cognitive aging.

Uric acid as a predictor of weight gain and cardiometabolic health in the Study of Novel Approaches to Weight Gain Prevention (SNAP) study.

Young adulthood is often a period of substantial weight gain increasing risk for obesity and cardiometabolic disease. Uric acid (UA), a clinical marker of oxidative stress, is associated with cardiometabolic dysfunction in established CVD, type 2 diabetes, and CKD. Yet, few trials have examined UA as a predictor of cardiometabolic risk in young, healthy populations, particularly in the context of weight gain prevention intervention. The purpose of this ancillary study was to examine UA in the Study of Novel Approaches to Weight Gain Prevention (SNAP), a randomized, controlled trial of weight gain prevention strategies in young healthy adults. UA was examined as a predictor of weight and cardiometabolic outcomes over 6 years; the impact of weight gain prevention interventions on UA was also examined. We found that higher baseline UA was a significant predictor of less favorable BMI, triglycerides, HDL, glucose, insulin, and HOMA, independent of age, sex, baseline weight, baseline level of the outcome variable, and weight gain prevention intervention. Additionally, ≥1% weight loss was associated with lower UA. UA is a promising biomarker for future weight gain and cardiometabolic risk in young adults that may respond to weight gain prevention.Clinical trial registration: clinicaltrials.gov identifier NCT01183689.

Effect of renin-angiotensin system antihypertensive medication use on cognitive function in diabetes mellitus with obesity or overweight: An ancillary study to the Action for Health in Diabetes (Look AHEAD) trial.

AIM: To determine whether antihypertensive medication (AHM) acting through the renin angiotensin system (RAS-AHM), compared with other AHM, can mitigate effects on cognitive function and risk for impairment in a population with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This secondary analysis of the randomized controlled Action for Health in Diabetes (Look AHEAD) study included 712 community-dwelling participants who were followed over 15 years. Logistic regression was used to relate RAS-AHM use to cognitive impairment, and linear regression was used to relate RAS-AHM use to domain-specific cognitive function after adjusting for potential confounders. RESULTS: A total of 563 individuals reported RAS-AHM use and 149 reported other-AHM use during the study. RAS-AHM users have college or higher education (53%), had higher baseline glycated haemoglobin (57 mmol/mol), and reported higher diabetes medication use (86%), while other-AHM users were more likely to be White (72%), obese (25%) and to have cardiovascular history (19%). RAS-AHM use was not associated with a reduced risk of dementia compared with other-AHM use. We did observe better executive function (Trail Making Test, part B, P < 0.04), processing speed (Digit Symbol Substitution Test, P < 0.004), verbal memory (Rey Auditory Verbal Learning Test-delayed recall, P < 0.005), and composite score (P < 0.008) among RAS-AHM users compared with other-AHM users. CONCLUSION: In this sample of adults with T2DM, free of dementia at baseline, we observed a slower decline in processing speed, executive function, verbal memory, and composite score among RAS-AHM users.

Red blood cell fatty acids and age-related macular degeneration in postmenopausal women.

PURPOSE: To evaluate the relationship between red blood cell (RBC) polyunsaturated fatty acid (PUFA) levels, and dietary PUFA and fish intake, with prevalent and incident age-related macular degeneration (AMD) in a US cohort of postmenopausal women. METHODS: This analysis included 1456 postmenopausal women from the Women's Health Initiative (WHI) Clinical Trials. RBC PUFAs were measured from fasting serum samples collected at WHI baseline. Dietary PUFAs and fish intake were assessed via food frequency questionnaires at baseline. There were 240 women who had prevalent AMD and 138 who self-reported AMD development over 9.5 years. Adjusted odds ratios and 95% confidence intervals were estimated for prevalent AMD by RBC PUFA levels, dietary PUFA intake, and frequency of fish consumption. Adjusted hazard ratios and 95% confidence intervals were estimated for incident AMD. A p-for-trend was estimated for continuous measures of dietary PUFA and fish intake. RESULTS: No significant association was found between prevalent or incident AMD and RBC docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), EPA, DHA, alpha-linolenic acid (ALA), linoleic acid (LA), or arachidonic acid (AA). A positive association was found between dietary intake of AA and odds of prevalent AMD (p-for-trend for continuous AA intake = 0.02) and between intake of LA/ALA and incident AMD (p-for-trend for continuous ratio of LA/ALA intake = 0.03). No statistically significant associations were found between AMD and dietary intake of PUFAs or fish. CONCLUSIONS: RBC PUFAs were not associated with AMD in this cohort. Overall, dietary analyses of PUFAs supported this, excepting dietary AA intake and intake of LA in proportion to ALA of which there were trends of increased risk.

The relationship between depressive symptoms and subtypes of mild cognitive impairment in post-menopausal women: Results from the Women's Health Initiative Memory Study.

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) (Alzheimer's 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 Women's 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 < 0.0001), but not non-amnestic MCI (HR = 1.39, 95% CI 0.91-2.14, p = 0.13) after controlling for demographic factors. This relationship between depressive symptoms and amnestic MCI remained consistent after controlling for lifestyle variables, cardiovascular risk factors, antidepressant use, and history of hormone therapy. There were no significant associations between depressive symptoms and incidence of PD. CONCLUSION: Depressive symptoms at baseline among postmenopausal older women are associated with higher incidence of amnestic MCI, suggesting that they may be an independent risk factor or part of the early prodrome of dementia.

Persistent, High Levels of Social Jetlag Predict Poor Weight Outcomes in a Weight Gain Prevention Study for Young adults.

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/m2) 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. ≥2 h) variable. RESULTS: 38% of participants had clinically-significant SJL at ≥ 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 (≥ 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.

B vitamin intakes modify the association between particulate air pollutants and incidence of all-cause dementia: Findings from the Women's Health Initiative Memory Study.

INTRODUCTION: Particulate air pollutants may induce neurotoxicity by increasing homocysteine levels, which can be lowered by high B vitamin intakes. Therefore, we examined whether intakes of three B vitamins (folate, B12 , and B6 ) modified the association between PM2.5 exposure and incidence of all-cause dementia. METHODS: This study included 7183 women aged 65 to 80 years at baseline. B vitamin intakes from diet and supplements were estimated by food frequency questionnaires at baseline. The 3-year average PM2.5 exposure was estimated using a spatiotemporal model. RESULTS: During a mean follow-up of 9 years, 342 participants developed all-cause dementia. We found that residing in locations with PM2.5 exposure above the regulatory standard (12 µg/m3 ) was associated with a higher risk of dementia only among participants with lower intakes of these B vitamins. DISCUSSION: This is the first study suggesting that the putative neurotoxicity of PM2.5 exposure may be attenuated by high B vitamin intakes.

The influence of social support on cognitive health in older women: a Women's Health Initiative study.

Social support is associated prospectively with cognitive decline and dementia among the elderly; however, little is known about the impact of social support on healthy neurological aging. The current study investigates whether perceived social support has an influence on neurological health among a large sample of healthy postmenopausal women. Social support and neuropsychological outcomes were measured annually for six years through the Women's Health Initiative Study of Cognitive Aging. In postmenopausal women, higher perceived social support was associated with significantly better overall neuropsychological functioning at baseline, especially in the domains of short-delay figural memory, short-delay verbal memory, and semantic fluency. No significant associations were found between social support and longitudinal changes in neuropsychological function over a median follow-up period of six years. Additionally, there was no significant relationship between social support and regional brain volumes. These findings suggest that social support is related to performance in a subset of neuropsychological domains and contributes to the existing literature that points to the importance of social support as a modifiable lifestyle factor that has the potential to help protect against the decline of cognitive aging, specifically among older adult women.

Effects of linagliptin vs glimepiride on cognitive performance in type 2 diabetes: results of the randomised double-blind, active-controlled CAROLINA-COGNITION study.

AIMS/HYPOTHESIS: Type 2 diabetes, particularly with concomitant CVD, is associated with an increased risk of cognitive impairment. We assessed the effect on accelerated cognitive decline (ACD) of the DPP-4 inhibitor linagliptin vs the sulfonylurea glimepiride in individuals with type 2 diabetes. METHODS: The CAROLINA-COGNITION study was part of the randomised, double-blind, active-controlled CAROLINA trial that evaluated the cardiovascular safety of linagliptin vs glimepiride in individuals with age ≥40 and ≤85 years and HbA1c 48-69 mmol/mol (6.5-8.5%) receiving standard care, excluding insulin therapy. Participants were randomised 1:1 using an interactive telephone- and web-based system and treatment assignment was determined by a computer-generated random sequence with stratification by center. The primary cognitive outcome was occurrence of ACD at end of follow-up, defined as a regression-based index score ≤16th percentile on either the Mini-Mental State Examination (MMSE) or a composite measure of attention and executive functioning, in participants with a baseline MMSE score ≥24. Prespecified additional analyses included effects on ACD at week 160, in subgroups (sex, age, race, ethnicity, depressive symptoms, cardiovascular risk, duration of type 2 diabetes, albuminuria), and absolute changes in cognitive performance. Participants, caregivers, and people involved in measurements, examinations or adjudication, were all masked to treatment assignment. RESULTS: Of 6033 participants recruited from hospital and primary care sites, 3163 (38.0% female, mean age/diabetes duration 64/7.6 years, MMSE score 28.5, HbA1c 54 mmol/mol [7.1%]) represent the CAROLINA-COGNITION cohort. Over median 6.1 years, ACD occurred in 27.8% (449/1618, linagliptin) vs 27.6% (426/1545, glimepiride), OR 1.01 (95% CI 0.86, 1.18). Also, no differences in ACD were observed at week 160 (OR 1.07 [0.91, 1.25]), between treatments across subgroups, or for absolute cognitive changes. CONCLUSIONS/INTERPRETATION: In a large, international outcome trial in people with relatively early type 2 diabetes at elevated cardiovascular risk, no difference in risk for ACD was observed between linagliptin and glimepiride over 6.1 years. FUNDING: This study was sponsored by Boehringer Ingelheim. TRIAL REGISTRATION: ClinicalTrials.gov NCT01243424.