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This research examines the relationship between personal mobility rate (number of lifetime moves/respondent's age) and health status. A contextual analysis is proposed in which the health consequences of relocation depend not only on the immediate circumstances surrounding a move, but also on the broader context of the individual's residential history, current life situation, and aspirations for the future. Two hundred and forty-two adult employees completed an initial survey of lifetime residential history, current residential desirability, employment experience, and perceived housing options for the future. Three months later, a panel group of 121 respondents completed a follow-up survey of emotional and physical well-being. Frequent relocation was directly associated with a greater number of illness-related symptoms, but the impact of mobility rate was largely mediated by psychological factors. Health problems were more prevalent among high-mobility individuals characterized by low rather than high levels of environmental exploratory tendency; among low-mobility persons reporting low versus high levels of residential choice and congruence; and among low residential-quality individuals who perceived future residential options to be unavailable rather than available. © 1983 Academic Press Inc. (London) Ltd.

Background: The Prostate Cancer Prevention Trial (PCPT)-a randomized placebo-controlled study of the efficacy of finasteride in preventing prostate cancer-offered the opportunity to prospectively study effects of finasteride and other covariates on the health-related quality of life of participants in a multiyear trial.Methods: We assessed three health-related quality-of-life domains (measured with the Health Survey Short Form-36: Physical Functioning, Mental Health, and Vitality scales) via questionnaires completed by PCPT participants at enrollment (3 months before randomization), at 6 months after randomization, and annually for 7 years. Covariate data obtained at enrollment from patient-completed questionnaires were included in our model. Mixed-effects model analyses and a cross-sectional presentation at three time points began at 6 months after randomization. All statistical tests were two-sided.Results: For the physical function outcome (n = 16 077), neither the finasteride main effect nor the finasteride interaction with time were statistically significant. The effects of finasteride on physical function were minor and accounted for less than a 1-point difference over time in Physical Functioning scores (mixed-effect estimate = 0.07, 95% confidence interval [CI] = -0.28 to 0.42, P = .71). Comorbidities such as congestive heart failure (estimate = -5.64, 95% CI = -7.96 to -3.32, P < .001), leg pain (estimate = -2.57, 95% CI = -3.04 to -2.10, P < .001), and diabetes (estimate = -1.31, 95% CI = -2.04 to -0.57, P < .001) had statistically significant negative effects on physical function, as did current smoking (estimate = -2.34, 95% CI = -2.97 to -1.71, P < .001) and time on study (estimate = -1.20, 95% CI = -1.36 to -1.03, P < .001). Finasteride did not have a statistically significant effect on the other two dependent variables, mental health and vitality, either in the mixed-effects analyses or in the cross-sectional analysis at any of the three time points.Conclusion: Finasteride did not negatively affect SF-36 Physical Functioning, Mental Health, or Vitality scores. [ABSTRACT FROM AUTHOR]

The present study tested whether baseline perceived social support and social integration predicted baseline and follow-up measures of health-related quality of life for 364 older adults with osteoarthritis. The findings are secondary analyses of a randomized controlled trial of an exercise intervention. Multiple regression analyses indicate that perceived social support was related to baseline measures of functioning in psychological (depressive symptoms, social functioning, and life satisfaction) and physical domains (self-rated disability, observed physical function, and perceived health), after accounting for demographic and clinical status factors. At 18-month follow-up (additionally controlling for exercise intervention and baseline outcomes), social support significantly predicted changes in psychosocial functioning, but was unrelated to changes in self-reported and observed physical health. The findings indicate that social support is an important predictor of long-term psychosocial outcomes, but is less important than baseline clinical status for physical health endpoints in this cohort of older adults. In contrast, social integration was not a consistent predictor of outcomes. [ABSTRACT FROM AUTHOR]

PURPOSE: The Research Support Core (RSC) began in the Women's Health Center of Excellence at Wake Forest University Health Sciences to (1) augment the institution's capacity to win grants in women's health and (2) assist women faculty in obtaining extramural funding. METHODS: The RSC began in July 2002 with a director, a research associate/scientific editor, and a budget specialist (total 0.7 full-time equivalents [FTE]). Its main functions were preaward grant assistance and education through workshops on grants and manuscripts. The purpose of this paper is to report the early experience (years 1 and 2: July 1, 2002, through June 30, 2004) of this service. RESULTS: From year 1 to year 2, the number of grant applications the RSC worked on rose 153% (from 17 to 43). Total dollars requested increased 2.5-fold, from 11.9 million US dollars in year 1 to 41.8 million US dollars in year 2. A total of 1.8 million US dollars was awarded or anticipated, with 27 applications pending. Overall, 38 faculty members from 18 academic departments received grant assistance. Of these, 100% of Core users who returned evaluations reported that they would use the RSC again and would recommend it to others. During this same period, nearly 500 people attended the 19 educational workshops on grants and manuscripts. CONCLUSIONS: As a result of this experience, the RSC was expanded and moved to the institution's Office of Research as a resource to all faculty. Assistance to women faculty and faculty conducting women's health research remain strong components of the RSC. [ABSTRACT FROM AUTHOR]

Context: The Women's Health Initiative Memory Study (WHIMS) previously found increased risk for dementia and no effect on mild cognitive impairment (MCI) in women treated with conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA).Objective: To determine the effects of CEE alone and CEE plus MPA on incidence of probable dementia and MCI in older women.Design, Setting, and Participants: Randomized, double-blind, placebo-controlled clinical trials of CEE (estrogen-alone trial) or CEE plus MPA (estrogen plus progestin trial) in community-dwelling women aged 65 to 79 years, conducted from June 1995 to July 8, 2002 (estrogen plus progestin; n = 4532), or to February 29, 2004 (estrogen-alone; n = 2947), in 39 of the 40 WHI clinical centers.Interventions: In the estrogen-alone trial, 1 daily tablet containing either 0.625 mg/d of CEE vs matching placebo; in the estrogen plus progestin trial, 1 daily tablet containing CEE (0.625 mg/d) plus MPA (2.5 mg/d) vs matching placebos.Main Outcome Measures: Probable dementia and MCI.Results: In the estrogen-alone trial, 47 participants were diagnosed with probable dementia, of whom 28 were assigned to CEE and 19 to placebo (hazard ratio [HR], 1.49; 95% confidence interval [CI], 0.83-2.66). Incidence rates for probable dementia in the estrogen-alone trial were statistically similar to those in the estrogen plus progestin trial (45 vs 22 per 10 000 person-years for CEE plus MPA vs placebo, respectively; P =.11). When data were pooled per the original WHIMS protocol, the overall HR for probable dementia was 1.76 (95% CI, 1.19-2.60; P =.005). After excluding participants with baseline Modified Mini-Mental State Examination scores at or below the screening cut point, the HR was 1.77 (95% CI, 0.74-4.23; P =.20) in the estrogen-alone trial and 2.19 (95% CI, 1.25-3.84; P =.006) in the pooled trials. In the estrogen-alone trial, 76 participants were diagnosed with MCI in the CEE group vs 58 in the placebo group (HR, 1.34; 95% CI, 0.95-1.89). In the combined trial data, the HR was similar (1.25; 95% CI, 0.97-1.60). In the estrogen-alone trial, 93 participants receiving CEE were diagnosed with either probable dementia or MCI vs 69 receiving placebo (HR, 1.38; 95% CI, 1.01-1.89; P =.04).Conclusions: Estrogen therapy alone did not reduce dementia or MCI incidence and increased the risk for both end points combined. Pooling data for estrogen alone and estrogen plus progestin resulted in increased risks for both end points. Use of hormone therapy to prevent dementia or cognitive decline in women 65 years of age or older is not recommended. [ABSTRACT FROM AUTHOR]

Context: The Women's Health Initiative Memory Study (WHIMS) previously reported that estrogen plus progestin therapy does not protect cognition among women aged 65 years or older. The effect of estrogen-alone therapy, also evaluated in WHIMS, on cognition has not been established for this population.Objectives: To determine whether conjugated equine estrogen (CEE) alters global cognitive function in older women and to compare its effect with CEE plus medroxyprogesterone acetate (CEE plus MPA).Design, Setting, and Participants: A randomized, double-blind, placebo-controlled ancillary study of the Women's Health Initiative (WHI), WHIMS evaluated the effect of CEE on incidence of probable dementia among community-dwelling women aged 65 to 79 years with prior hysterectomy from 39 US academic centers that started in June 1995. Of 3200 eligible women free of probable dementia enrolled in the WHI, 2947 (92.1%) were enrolled in WHIMS. Analyses were conducted on the 2808 women (95.3%) with a baseline and at least 1 follow-up measure of global cognitive function before the trial's termination on February 29, 2004.Interventions: Participants received 1 daily tablet containing either 0.625 mg of CEE (n = 1387) or matching placebo (n = 1421).Main Outcome Measure: Global cognitive function measured annually with the Modified Mini-Mental State Examination (3MSE).Results: During a mean follow-up of 5.4 years, mean (SE) 3MSE scores were 0.26 (0.13) units lower than among women assigned to CEE compared with placebo (P =.04). For pooled hormone therapy (CEE combined with CEE plus MPA), the mean (SE) decrease was 0.21 (0.08; P =.006). Removing women with dementia, mild cognitive impairment, or stroke from the analyses lessened these differences. The adverse effect of hormone therapy was more pronounced among women with lower cognitive function at baseline (all P<.01). For women assigned to CEE compared with placebo, the relative risk of having a 10-unit decrease in 3MSE scores (>2 SDs) was estimated to be 1.47 (95% confidence interval, 1.04-2.07).Conclusion: For women aged 65 years or older, hormone therapy had an adverse effect on cognition, which was greater among women with lower cognitive function at initiation of treatment. [ABSTRACT FROM AUTHOR]

Abstract Background The efficacy of non-pharmacological intervention approaches such as physical activity, strength, and cognitive training for improving brain health has not been established. Before definitive trials are mounted, important design questions on participation/adherence, training and interventions effects must be answered to more fully inform a full-scale trial. Methods SHARP-P was a single-blinded randomized controlled pilot trial of a 4-month physical activity training intervention (PA) and/or cognitive training intervention (CT) in a 2 × 2 factorial design with a health education control condition in 73 community-dwelling persons, aged 70-85 years, who were at risk for cognitive decline but did not have mild cognitive impairment. Results Intervention attendance rates were higher in the CT and PACT groups: CT: 96%, PA: 76%, PACT: 90% (p=0.004), the interventions produced marked changes in cognitive and physical performance measures (p≤0.05), and retention rates exceeded 90%. There were no statistically significant differences in 4-month changes in composite scores of cognitive, executive, and episodic memory function among arms. Four-month improvements in the composite measure increased with age among participants assigned to physical activity training but decreased with age for other participants (intervention*age interaction p = 0.01). Depending on the choice of outcome, two-armed full-scale trials may require fewer than 1,000 participants (continuous outcome) or 2,000 participants (categorical outcome). Conclusions Good levels of participation, adherence, and retention appear to be achievable for participants through age 85 years. Care should be taken to ensure that an attention control condition does not attenuate intervention effects. Depending on the choice of outcome measures, the necessary sample sizes to conduct four-year trials appear to be feasible. Trial Registration Clinicaltrials.gov Identifier: NCT00688155

Objective: This mixed methods study examines the relationship between outcome expectations, self-efficacy, and self-care behaviors in individuals with type 2 diabetes (T2DM). It also explores the personal values motivating these behaviors through in-depth interviews., Methods: Adults with T2DM (n = 108, M age = 57 years, 58% female, 48% Black) completed questionnaires and participated in in-depth interviews using a laddering technique., Results: Ordinary least squares regression models were used to analyze the relationships between self-efficacy, outcome expectations, and four self-care behaviors (physical activity, dietary choices, blood glucose monitoring, and medication usage). The findings indicate that self-efficacy is significantly and positively associated with diet and physical activity. Both outcome expectations for blood glucose testing and self-efficacy are significantly and positively associated with self-reported monitoring. However, neither outcome expectation nor self-efficacy is associated with medication usage. The in-depth interviews revealed three common values related to self-care behaviors: maintaining health and longevity, agentic values of self-control, achievement, and self-esteem, and a sense of belonging., Conclusions: This study sheds light on the complexity of diabetes self-management, offering insights into individuals' values, behavioral strategies, and the influence of control perceptions on this relationship, revealing both differences and commonalities in stated values., Practice Implications: By understanding how personal values drive diabetes self-care behaviors, practitioners can assist patients in establishing meaningful connections between their values and the challenges of living with diabetes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Heather L. Black, Ph.D. is employed by the funding agency. The authors from Wake Forest University and Wake Forest School of Medicine declare that they have no conflict of interest, have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Importance: Approximately 55 million people in the US and approximately 1.1 billion people worldwide are postmenopausal women. To inform clinical practice about the health effects of menopausal hormone therapy, calcium plus vitamin D supplementation, and a low-fat dietary pattern, the Women's Health Initiative (WHI) enrolled 161 808 postmenopausal US women (N = 68 132 in the clinical trials) aged 50 to 79 years at baseline from 1993 to 1998, and followed them up for up to 20 years., Observations: The WHI clinical trial results do not support hormone therapy with oral conjugated equine estrogens plus medroxyprogesterone acetate for postmenopausal women or conjugated equine estrogens alone for those with prior hysterectomy to prevent cardiovascular disease, dementia, or other chronic diseases. However, hormone therapy is effective for treating moderate to severe vasomotor and other menopausal symptoms. These benefits of hormone therapy in early menopause, combined with lower rates of adverse effects of hormone therapy in early compared with later menopause, support initiation of hormone therapy before age 60 years for women without contraindications to hormone therapy who have bothersome menopausal symptoms. The WHI results do not support routinely recommending calcium plus vitamin D supplementation for fracture prevention in all postmenopausal women. However, calcium and vitamin D are appropriate for women who do not meet national guidelines for recommended intakes of these nutrients through diet. A low-fat dietary pattern with increased fruit, vegetable, and grain consumption did not prevent the primary outcomes of breast or colorectal cancer but was associated with lower rates of the secondary outcome of breast cancer mortality during long-term follow-up., Conclusions and Relevance: For postmenopausal women, the WHI randomized clinical trials do not support menopausal hormone therapy to prevent cardiovascular disease or other chronic diseases. Menopausal hormone therapy is appropriate to treat bothersome vasomotor symptoms among women in early menopause, without contraindications, who are interested in taking hormone therapy. The WHI evidence does not support routine supplementation with calcium plus vitamin D for menopausal women to prevent fractures or a low-fat diet with increased fruits, vegetables, and grains to prevent breast or colorectal cancer. A potential role of a low-fat dietary pattern in reducing breast cancer mortality, a secondary outcome, warrants further study.

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., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

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., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

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., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: The coronavirus disease 2019 (COVID-19) pandemic is a health crisis of which older adults are a high-risk group for severe illness and mortality. The objectives of this article are to describe the methods and responses to a COVID-19 survey administered by the Women's Health Initiative (WHI) to assess the impact of the pandemic on older women., Methods: WHI is an ongoing prospective cohort study that recruited 161 808 postmenopausal women from 1993 to 1998. From June 2020 to October 2020, participants in active follow-up were surveyed by mail, phone, or online to assess health and well-being, living situations, lifestyle, health care, and self-reported COVID-19 testing, treatment, and preventive behaviors., Results: Of 64 061 eligible participants, 49 695 (average age 83.6 years ± 5.6) completed the COVID-19 survey (response rate 77.6%). Many participants reported very good or good well-being (75.6%). Respondents reported being very concerned about the pandemic (51.1%; more common in urban compared to rural areas), with 6.9% reporting disruptions in living arrangements and 9.7% reporting changes in medication access. Participants (54.4%) reported physical activity levels were much less or somewhat less compared to levels before the pandemic, and this was more pronounced in urban areas versus rural areas (55.3% vs 44.4%). Participants engaged in preventive behaviors including wearing a face mask (93.2%). A total of 18.9% reported testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), among whom 3.5% (n = 311) reported testing positive., Conclusions: In this nationwide survey of older U.S. women, the COVID-19 pandemic was associated with impacts on health and well-being, living situations, lifestyle, health care access, and SARS-CoV-2 testing and preventive behaviors., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The association of cognitive function with symptoms of psychological distress during the coronavirus disease 2019 (COVID-19) pandemic or adherence to COVID-19 protective health behaviors is not well-understood., Methods: We examined 2 890 older women from the Women's Health Initiative cohort. Prepandemic (ie, within 12 months prior to pandemic onset) and peripandemic global cognitive function scores were assessed with the modified Telephone Interview for Cognitive Status (TICS-m). Anxiety, stress, and depressive symptom severity during the pandemic were assessed using validated questionnaires. We examined adherence to protective behaviors that included safe hygiene, social distancing, mask wearing, and staying home. Multivariable models were adjusted for age, race, ethnicity, education, region of residence, alcohol intake, and comorbidities., Results: Every 5-point lower prepandemic TICS-m score was associated with 0.33-point mean higher (95% confidence interval [CI], 0.20, 0.45) perceived stress and 0.20-point mean higher (95% CI, 0.07, 0.32) depressive symptom severity during the pandemic. Higher depressive symptom severity, but not anxiety or perceived stress, was associated with a 0.69-point (95% CI, -1.13, -0.25) mean decline in TICS-m from the prepandemic to peripandemic period. Every 5-point lower peripandemic TICS-m score was associated with 12% lower odds ratio (OR, 0.88; 95% CI, 0.80, 0.97) of practicing safe hygiene., Conclusions: Among older women, we observed that: (a) lower prepandemic global cognitive function was associated with higher stress and depressive symptom severity during the pandemic; (b) higher depressive symptom severity during the pandemic was associated with cognitive decline; and (c) lower global cognitive function during the pandemic was associated with lower odds of practicing safe hygiene., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© 2022 John Wiley & Sons Ltd.)

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 Women's Health Initiative Clinical Trials and Women's 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 (<7 h) sleep duration was unrelated to PD. Finally, the presence of obstructive sleep apnea risk factors was not associated with PD., Conclusions: Among postmenopausal women, sleep disturbance was associated with approximately 10% to 30% increased PD risk after ∼16 years follow-up. Prospective cohort studies with objective exposures and adjudicated outcomes that include men and women of diverse backgrounds are required to confirm and extend these findings., Competing Interests: Financial disclosure/conflicts of interest: M.E. has received funding from Boehriinger-Ingelheim Pharmaceuticals. M.N. receives grant funding from the Merck Foundation for a research study unrelated to the article in question. The other authors have nothing to disclose., (Copyright © 2022 by The North American Menopause Society.)

Objective: To examine whether late-life exposure to PM 2.5 (particulate matter with aerodynamic diameters <2.5 µm) contributes to progressive brain atrophy predictive of Alzheimer disease (AD) using a community-dwelling cohort of women (age 70-89 years) with up to 2 brain MRI scans (MRI-1, 2005-2006; MRI-2, 2010-2011)., Methods: AD pattern similarity (AD-PS) scores, developed by supervised machine learning and validated with MRI data from the Alzheimer's Disease Neuroimaging Initiative, were used to capture high-dimensional gray matter atrophy in brain areas vulnerable to AD (e.g., amygdala, hippocampus, parahippocampal gyrus, thalamus, inferior temporal lobe areas, and midbrain). Using participants' addresses and air monitoring data, we implemented a spatiotemporal model to estimate 3-year average exposure to PM 2.5 preceding MRI-1. General linear models were used to examine the association between PM 2.5 and AD-PS scores (baseline and 5-year standardized change), accounting for potential confounders and white matter lesion volumes., Results: For 1,365 women 77.9 ± 3.7 years of age in 2005 to 2006, there was no association between PM 2.5 and baseline AD-PS score in cross-sectional analyses (β = -0.004; 95% confidence interval [CI] -0.019 to 0.011). Longitudinally, each interquartile range increase of PM 2.5 (2.82 µg/m 3 ) was associated with increased AD-PS scores during the follow-up, equivalent to a 24% (hazard ratio 1.24, 95% CI 1.14-1.34) increase in AD risk over 5 years (n = 712, age 77.4 ± 3.5 years). This association remained after adjustment for sociodemographics, intracranial volume, lifestyle, clinical characteristics, and white matter lesions and was present with levels below US regulatory standards (<12 µg/m 3 )., Conclusions: Late-life exposure to PM 2.5 is associated with increased neuroanatomic risk of AD, which may not be explained by available indicators of cerebrovascular damage., (© 2020 American Academy of Neurology.)

Background: We examined common patterns of home environmental modification (HEM) use and associated major (including disability-, cardiovascular-, and cancer-related) health conditions and events among older women., Methods: Women, aged 78.6 ± 6.3 years (n = 71,257), self-reported utilization of nine types of HEMs (hand rails, grab bars, ramps, nonslip surfaces, tacking carpets/rugs, decreasing clutter, increasing lighting, raised sink/counter heights, other). Concurrent history of major health conditions and events was collected. Odds ratios (ORs) were estimated based on overall HEM use and four latent classes (low HEM use [56%], rails/grab bars [20%], lighting/decluttering [18%], high HEM use [5%]), adjusted for age, marital status, race/ethnicity, education, depression, and obesity., Results: Fifty-five percent of women reported using any HEM (overall), with strongest associations among disability-related conditions. Activities of daily living limitations were strongly associated with high HEM use (OR = 8.16, 95% confidence interval [CI] = 6.62-10.05), railing/grab bar use (OR = 4.02, 95% CI = 3.26-4.95), and lighting/declutter use (OR = 1.87, 95% CI = 1.40-2.50) versus low HEM use. Recent falls were positively associated with overall HEM use (OR = 1.79, 95% CI = 1.72-1.87); high HEM use (OR = 2.89, 95% CI = 2.64-3.16), railings/grab bars use (OR = 2.32, 95% CI = 2.18-2.48), and lighting/declutter use (OR = 1.93, 95% CI = 1.79-2.08) were positively associated with recent falls. Modest associations were observed between HEM use and select (ie, atrial fibrillation, heart valve disease, stroke) cardiovascular outcomes., Conclusions: Among older women, disability-related conditions, including functional limitations and recent falls, were strongly associated with overall HEM use, high HEM use, and railings/grab bar use., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Evidence suggests exposure to particulate matter with aerodynamic diameter <2.5 μm (PM2.5) may increase the risk for Alzheimer's disease and related dementias. Whether PM2.5 alters brain structure and accelerates the preclinical neuropsychological processes remains unknown. Early decline of episodic memory is detectable in preclinical Alzheimer's disease. Therefore, we conducted a longitudinal study to examine whether PM2.5 affects the episodic memory decline, and also explored the potential mediating role of increased neuroanatomic risk of Alzheimer's disease associated with exposure. Participants included older females (n = 998; aged 73-87) enrolled in both the Women's Health Initiative Study of Cognitive Aging and the Women's Health Initiative Memory Study of Magnetic Resonance Imaging, with annual (1999-2010) episodic memory assessment by the California Verbal Learning Test, including measures of immediate free recall/new learning (List A Trials 1-3; List B) and delayed free recall (short- and long-delay), and up to two brain scans (MRI-1: 2005-06; MRI-2: 2009-10). Subjects were assigned Alzheimer's disease pattern similarity scores (a brain-MRI measured neuroanatomical risk for Alzheimer's disease), developed by supervised machine learning and validated with data from the Alzheimer's Disease Neuroimaging Initiative. Based on residential histories and environmental data on air monitoring and simulated atmospheric chemistry, we used a spatiotemporal model to estimate 3-year average PM2.5 exposure preceding MRI-1. In multilevel structural equation models, PM2.5 was associated with greater declines in immediate recall and new learning, but no association was found with decline in delayed-recall or composite scores. For each interquartile increment (2.81 μg/m3) of PM2.5, the annual decline rate was significantly accelerated by 19.3% [95% confidence interval (CI) = 1.9% to 36.2%] for Trials 1-3 and 14.8% (4.4% to 24.9%) for List B performance, adjusting for multiple potential confounders. Long-term PM2.5 exposure was associated with increased Alzheimer's disease pattern similarity scores, which accounted for 22.6% (95% CI: 1% to 68.9%) and 10.7% (95% CI: 1.0% to 30.3%) of the total adverse PM2.5 effects on Trials 1-3 and List B, respectively. The observed associations remained after excluding incident cases of dementia and stroke during the follow-up, or further adjusting for small-vessel ischaemic disease volumes. Our findings illustrate the continuum of PM2.5 neurotoxicity that contributes to early decline of immediate free recall/new learning at the preclinical stage, which is mediated by progressive atrophy of grey matter indicative of increased Alzheimer's disease risk, independent of cerebrovascular damage., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: As people age and the incidence of dementia increases, studies of cognitive function continue to be of importance. Ascertaining cognitive data through different mechanisms is necessary to address missing data concerns., Methods: The Dementia Questionnaire (DQ), which utilizes proxy-based assessments, is a potential tool to determine cognitive status in participants no longer being followed per traditional study protocol. The DQ is currently being used in the Supplemental Case Ascertainment Protocol (SCAP), which is being conducted in an ongoing study of postmenopausal women as part of the Women's Health Initiative Memory Study (WHIMS)., Results: Ninety-four percent of the 1260 SCAP participants were eligible because of being deceased. Those who are SCAP eligible were older, were less likely to be a minority, and were more likely to have hypertension, diabetes, and prior history of cardiovascular disease (CVD) as well as being a past or current smoker. SCAP added 109 cases of probable dementia to WHIMS. Risk factor relationships were modified upon inclusion of the SCAP cases including an attenuation of a hormone therapy effect and discovery of a hypertension effect., Conclusions: Augmenting clinic-based cases with proxy-based assessments is feasible and leads to increased incident cases of dementia. When planning future clinical trials, it may be of study benefit to include a protocol of proxy-based assessments, develop strong relationships with proxies early on in the study, and attempt to maintain this relationship throughout the lifespan of the trial., (© 2019 John Wiley & Sons, Ltd.)

Background: Large simple trials are potentially efficient and cost-effective approaches to assess interventions to preserve cognitive function in older adults. High-dose cocoa flavanols supplementation is a promising intervention that warrants additional testing. We describe the design, recruitment success, and baseline characteristics of the Cocoa Supplement and Multivitamin Outcomes Study for the Mind (COSMOS-Mind) trial., Methods: COSMOS-Mind is an ancillary study to the large-scale and predominantly mail-based COSMOS randomized controlled clinical trial. COSMOS is assessing whether cocoa extract (including 600 mg/d cocoa flavanols) and a multivitamin reduce risks for major cardiovascular events and total invasive cancer. COSMOS-Mind uses telephone-based interviews to assess cognitive function and impairment to determine whether cocoa flavanols benefit cognitive function in adults aged 65 years or older, targeting the enrollment of 2000 participants to provide >90% statistical power across 3 years of annual follow-up., Results: Of the 3224 COSMOS screenees who expressed interest in COSMOS-Mind, 2350 (76%) successfully completed baseline cognitive assessments and 2262 (96%) geographically diverse, eligible individuals were ultimately enrolled over one year. At baseline, the primary outcome, a composite of cognitive test scores, was inversely associated with age in a manner consistent with assumptions used in projections of statistical power., Conclusions: Older adults are willing to enroll in large simple trials that include telephone-based cognitive assessments. Embedding these trials in large studies of other health outcomes is efficient and expands the scientific knowledge gained from the research. ClinicalTrials.gov Identifiers: NCT03035201 (COSMOS-Mind); NCT102422745 (parent COSMOS)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Reducing symptom burden is often secondary to risk factor control in diabetes. Symptom burden with comorbid medical conditions and the need for symptom palliation are not well defined. Although neuropathy is one of the most frequent occurring comorbidities of diabetes, patient experience is inconsistent. Using in-depth interview, we assessed patients' perspectives of pain experienced through neuropathy and the impact on type 2 diabetes management. Areas covered: Participants completed a structured telephone interview during which perspectives on diabetes and its management occurred. Data were analyzed iteratively using content analysis and extracted themes came from reduced data. Interview data were triangulated with clinical data from electronic health records. Expert opinion: During interviews, 41% of patients reported pain interfered with their lives. Three pain-related themes emerged from interviews, augmented by descriptions of how people experience and cope with pain. Themes included: (1) people know what neuropathy is and attribute their pain to it; (2) neuropathic pain seems insurmountable at times; and (3) pain can lead to feeling down or hopeless. Pain, a common comorbidity in diabetes, is a primary driver of patient suffering. Understanding how patients experience pain paves the way for creative interventions to manage it better among those living with diabetes.

Objective: While a number of single nucleotide polymorphisms (SNPs) associated with Alzheimer's disease (AD) or cognitive impairment have been identified, independent replications remain the only way to validate proposed signals. We investigated SNPs in candidate genes associated with either cognitive impairment or AD pathogenesis and their relationships with probable dementia (PD) in the Women's Health Initiative Memory Study (WHIMS)., Methods: We analyzed 96 SNPs across five genes (APOE/TOMM40, BDNF, COMT, SORL1, and KIBRA) in 2857 women (ages ≥65) from the WHIMS randomized trials of hormone therapy using a custom Illumina GoldenGate assay; 19% of the sample were MCI (N = 165) or PD (N = 387), and the remaining 81% were free of cognitive impairment. SNP associations were evaluated for PD in non-Hispanic whites adjusting for age and HT using logistic regression under an additive genetic model., Results: One SNP (rs157582), located in the TOMM40 gene nearby APOE, was associated with the PD phenotype based on a P value accounting for multiple comparisons. An additional 12 SNPs were associated with the PD phenotype at P ≤ 0.05 (APOE: rs405509, rs439401; TOMM40: rs8106922, and KIBRA: rs4320284, rs11740112, rs10040267, rs13171394, rs6555802, rs2241368, rs244904, rs6555805, and rs10475878). Results of the sensitivity analyes excluding MCI were similar, with addition of COMT rs737865 and BDNF rs1491850 (P ≤ 0.05)., Conclusions: Our results in older women provide supporting evidence that the APOE/TOMM40 genes confer dementia risk and extend these findings to COMT, BDNF, and KIBRA. Our findings may lead to a better understanding of the role these genes play in cognition and cognitive impairment., (© 2019 John Wiley & Sons, Ltd.)

Introduction: In a geographically diverse sample of women, we asked whether cognitive reserve (CR) is best viewed as a general or cognitive domain-specific construct and whether some cognitive reserve domains but not others exert protective effects on risk of developing mild cognitive impairment (MCI) or dementia., Methods: Estimates of general and domain-specific CR were derived via variance decomposition in 972 cognitively intact women from the Women's Health Initiative Study of Cognitive Aging and Women's Health Memory Study Magnetic Resonance Imaging. Women were then followed up for 13 years., Results: General CR was the strongest predictor of reduced risk for both MCI and dementia, compared to domain-specific CR measures. Verbal memory, figural memory, and spatial CR were independently protective of MCI, but only verbal memory was independently associated with reduced risk for dementia., Discussion: Cognitive reserve is a heterogenous construct with valid quantitative measures identifiable across different neuropsychological processes associated with MCI and dementia.

Background: Cognitive 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., Methods: A 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., Results: In 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., Conclusions: In 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.

Background: Positive affect (PA) and negative affect (NA) reflect subjective emotional experiences. Although related to depression and anxiety, these dimensions are distinct constructs representing affective states and patterns. Prior studies suggest that elevated depressive symptoms are associated with risk of mild cognitive impairment (MCI) and probable dementia, but whether affective states are associated with cognitive impairment is still unknown. The present study examined relationships between baseline affective states and cognitive impairment (MCI, probable dementia) in nondepressed women., Method: Baseline PA and NA were assessed in postmenopausal women (N = 2,137; mean age = 73.8 years) from the Women's Health Initiative Study of Cognitive Aging (WHISCA) using the Positive and Negative Affect Schedule (PANAS). Women were followed annually for an average of 11.3 years; those with elevated depressive symptoms at baseline were excluded., Results: Higher NA was associated with a higher risk of MCI and probable dementia, even after adjusting for important covariates including age, education, sociodemographic, lifestyle, and cardiovascular risk factors, global cognition, and hormone therapy assignment at baseline. PA was not significantly associated with either outcome., Conclusions: We present the first evidence to date that greater NA, even in the absence of elevated depressive symptoms, is associated with higher risk of MCI and dementia. This suggests that NA may be an important, measureable and potentially modifiable risk factor for age-related cognitive decline.

Importance: Health outcomes from the Women's Health Initiative Estrogen Plus Progestin and Estrogen-Alone Trials have been reported, but previous publications have generally not focused on all-cause and cause-specific mortality., Objective: To examine total and cause-specific cumulative mortality, including during the intervention and extended postintervention follow-up, of the 2 Women's Health Initiative hormone therapy trials., Design, Setting, and Participants: Observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014., Interventions: Conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8506) vs placebo (n = 8102) for 5.6 years (median) or CEE alone (n = 5310) vs placebo (n = 5429) for 7.2 years (median)., Main Outcomes and Measures: All-cause mortality (primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) in the 2 trials pooled and in each trial individually, with prespecified analyses by 10-year age group based on age at time of randomization., Results: Among 27 347 women who were randomized (baseline mean [SD] age, 63.4 [7.2] years; 80.6% white), mortality follow-up was available for more than 98%. During the cumulative 18-year follow-up, 7489 deaths occurred (1088 deaths during the intervention phase and 6401 deaths during postintervention follow-up). All-cause mortality was 27.1% in the hormone therapy group vs 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.94-1.03]) in the overall pooled cohort; with CEE plus MPA, the HR was 1.02 (95% CI, 0.96-1.08); and with CEE alone, the HR was 0.94 (95% CI, 0.88-1.01). In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92-1.08 [8.9 % with hormone therapy vs 9.0% with placebo]); for total cancer mortality, the HR was 1.03 (95% CI, 0.95-1.12 [8.2 % with hormone therapy vs 8.0% with placebo]); and for other causes, the HR was 0.95 (95% CI, 0.88-1.02 [10.0% with hormone therapy vs 10.7% with placebo]), and results did not differ significantly between trials. When examined by 10-year age groups comparing younger women (aged 50-59 years) to older women (aged 70-79 years) in the pooled cohort, the ratio of nominal HRs for all-cause mortality was 0.61 (95% CI, 0.43-0.87) during the intervention phase and the ratio was 0.87 (95% CI, 0.76-1.00) during cumulative 18-year follow-up, without significant heterogeneity between trials., Conclusions and Relevance: Among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years., Trial Registration: clinicaltrials.gov Identifier: NCT00000611.

Background: Postmenopausal hormone therapy may have long-term effects on cognitive function depending on women's age., Methods: Postintervention follow-up was conducted with annual cognitive assessments of two randomized controlled clinical trial cohorts, beginning an average of 6-7 years after study medications were terminated: 1,376 women who had enrolled in the Women's Health Initiative when aged 50-54 years and 2,880 who had enrolled when aged 65-79 years. Women had been randomly assigned to 0.625mg/d conjugated equine estrogens (CEE) for those with prior hysterectomy (mean 7.1 years), CEE with 2.5mg/d medroxyprogesterone acetate for those without prior hysterectomy (mean 5.4 years), or matching placebos., Results: Hormone therapy, when prescribed to women aged 50-54 years, had no significant long-term posttreatment effects on cognitive function and on changes in cognitive function. When prescribed to older women, it was associated with long-term mean (SE) relative decrements (standard deviation units) in global cognitive function of 0.081 (0.029), working memory of 0.070 (0.025), and executive function of 0.054 (0.023), all p < .05. These decrements were relatively stable over time. Findings did not vary depending on the hormone therapy regimen, prior use, or years from last menstrual period. Mean intervention effects were small; however, the largest were comparable in magnitude to those seen during the trial's active intervention phase., Conclusions: CEE-based hormone therapy delivered near the time of menopause provides neither cognitive benefit nor detriment. If administered in older women, it results in small decrements in several cognitive domains that remain for many years., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Most cognitive functions decline with age. Prior studies suggest that testosterone treatment may improve these functions., Objective: To determine if testosterone treatment compared with placebo is associated with improved verbal memory and other cognitive functions in older men with low testosterone and age-associated memory impairment (AAMI)., Design, Setting, and Participants: The Testosterone Trials (TTrials) were 7 trials to assess the efficacy of testosterone treatment in older men with low testosterone levels. The Cognitive Function Trial evaluated cognitive function in all TTrials participants. In 12 US academic medical centers, 788 men who were 65 years or older with a serum testosterone level less than 275 ng/mL and impaired sexual function, physical function, or vitality were allocated to testosterone treatment (n = 394) or placebo (n = 394). A subgroup of 493 men met criteria for AAMI based on baseline subjective memory complaints and objective memory performance. Enrollment in the TTrials began June 24, 2010; the final participant completed treatment and assessment in June 2014., Interventions: Testosterone gel (adjusted to maintain the testosterone level within the normal range for young men) or placebo gel for 1 year., Main Outcomes and Measures: The primary outcome was the mean change from baseline to 6 months and 12 months for delayed paragraph recall (score range, 0 to 50) among men with AAMI. Secondary outcomes were mean changes in visual memory (Benton Visual Retention Test; score range, 0 to -26), executive function (Trail-Making Test B minus A; range, -290 to 290), and spatial ability (Card Rotation Test; score range, -80 to 80) among men with AAMI. Tests were administered at baseline, 6 months, and 12 months., Results: Among the 493 men with AAMI (mean age, 72.3 years [SD, 5.8]; mean baseline testosterone, 234 ng/dL [SD, 65.1]), 247 were assigned to receive testosterone and 246 to receive placebo. Of these groups, 247 men in the testosterone group and 245 men in the placebo completed the memory study. There was no significant mean change from baseline to 6 and 12 months in delayed paragraph recall score among men with AAMI in the testosterone and placebo groups (adjusted estimated difference, -0.07 [95% CI, -0.92 to 0.79]; P = .88). Mean scores for delayed paragraph recall were 14.0 at baseline, 16.0 at 6 months, and 16.2 at 12 months in the testosterone group and 14.4 at baseline, 16.0 at 6 months, and 16.5 at 12 months in the placebo group. Testosterone was also not associated with significant differences in visual memory (-0.28 [95% CI, -0.76 to 0.19]; P = .24), executive function (-5.51 [95% CI, -12.91 to 1.88]; P = .14), or spatial ability (-0.12 [95% CI, -1.89 to 1.65]; P = .89)., Conclusions and Relevance: Among older men with low testosterone and age-associated memory impairment, treatment with testosterone for 1 year compared with placebo was not associated with improved memory or other cognitive functions., Trial Registration: clinicaltrials.gov Identifier: NCT00799617.

Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer's disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women's Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ɛ4/4 carriers. Female EFAD transgenic mice (5xFAD +/- /human APOE ɛ3 or ɛ4 +/+ ) with 225 h exposure to urban nanosized PM (nPM) over 15 weeks showed increased cerebral β-amyloid by thioflavin S for fibrillary amyloid and by immunocytochemistry for Aβ deposits, both exacerbated by APOE ɛ4. Moreover, nPM exposure increased Aβ oligomers, caused selective atrophy of hippocampal CA1 neurites, and decreased the glutamate GluR1 subunit. Wildtype C57BL/6 female mice also showed nPM-induced CA1 atrophy and GluR1 decrease. In vitro nPM exposure of neuroblastoma cells (N2a-APP/swe) increased the pro-amyloidogenic processing of the amyloid precursor protein (APP). We suggest that airborne PM exposure promotes pathological brain aging in older women, with potentially a greater impact in ɛ4 carriers. The underlying mechanisms may involve increased cerebral Aβ production and selective changes in hippocampal CA1 neurons and glutamate receptor subunits., Competing Interests: The authors declare no conflict of interest.

Background: Nonhuman studies suggest a protective effect of caffeine on cognition. Although human literature remains less consistent, reviews suggest a possible favorable relationship between caffeine consumption and cognitive impairment or dementia. We investigated the relationship between caffeine intake and incidence of cognitive impairment or probable dementia in women aged 65 and older from the Women's Health Initiative Memory Study., Methods: All women with self-reported caffeine consumption at enrollment were included (N = 6,467). In 10 years or less of follow-up with annual assessments of cognitive function, 388 of these women received a diagnosis of probable dementia based on a 4-phase protocol that included central adjudication. We used proportional hazards regression to assess differences in the distributions of times until incidence of probable dementia or composite cognitive impairment among women grouped by baseline level of caffeine intake, adjusting for risk factors (hormone therapy, age, race, education, body mass index, sleep quality, depression, hypertension, prior cardiovascular disease, diabetes, smoking, and alcohol consumption)., Results: Women consuming above median levels (mean intake = 261mg) of caffeine intake for this group were less likely to develop incident dementia (hazard ratio = 0.74, 95% confidence interval [0.56, 0.99], p = .04) or any cognitive impairment (hazard ratio = 0.74, confidence interval [0.60, 0.91], p = .005) compared to those consuming below median amounts (mean intake = 64mg) of caffeine for this group., Conclusion: Our findings suggest lower odds of probable dementia or cognitive impairment in older women whose caffeine consumption was above median for this group and are consistent with the existing literature showing an inverse association between caffeine intake and age-related cognitive impairment., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Laboratory-based polysomnography (PSG) is the gold standard assessment of sleep disordered breathing (SDB). In large cohort studies and clinical trials, however, these overnight procedures can be expensive and burdensome to participants, especially older adults. In preparation for a large observational study, we determined the feasibility of self-administering two devices mailed to participants' homes that estimate indices of SDB., Methods: In two separate studies, older women enrolled in the Women's Health Initiative (WHI) Memory Study extension aged mean (SD) 85.77 (2.98) years who were not using supplemental oxygen and consented to being in the feasibility study completed either an in-home, self-administered overnight sleep assessment using a multi-sensor device that measured oximetry, nasal pressure, chest effort, and snoring (ApneaLink(TM)) (N = 58), or a wrist-worn oximeter (NoninWristOx2(TM)) (N = 33). A follow-up questionnaire assessed the devices' acceptability and important sleep-related exposures., Results: Although the multi-sensor device was assessed only in older women with no cognitive impairment, the proportion of completed interpretable sleep studies was low (54 %) and participants reported needing help to administer the device successfully. In contrast, the wrist-worn device was used in women with either no or mild cognitive impairment (MCI), completion rates were higher (100 %), and women reported being able to administer the device independently., Conclusions: These studies demonstrated that home-based self-administered assessments of SDB are feasible in older adults with and without cognitive impairment using wrist-worn oximetry. These data support the feasibility of using simple oximetry measurements to provide indices of overnight intermittent hypoxemia in large observational studies and clinical trials.

Background: We examined physical functioning (PF) trajectories (maintaining, slowly declining, and rapidly declining) spanning 15 years in older women aged 65-80 and protective factors that predicted better current levels and less decline in functional independence outcomes after age 80., Methods: Women's Health Initiative extension participants who met criteria (enrolled in either the clinical trial or observational study cohort, >80 years at the data release cutoff, PF survey data from initial enrollment to age 80, and functional independence survey data after age 80) were included in these analyses (mean [SD] age = 84.0 [1.4] years; N = 10,478). PF was measured with the SF-36 (mean = 4.9 occasions). Functional independence was measured by self-reported level of dependence in basic and instrumental activities of daily living (ADLs and IADLs) (mean = 3.4 and 3.3 occasions)., Results: Maintaining consistent PF in older adulthood extends functional independence in ADL and IADL in late-life. Protective factors shared by ADL and IADL include maintaining PF over time, self-reported excellent or very good health, no history of hip fracture after age 55, and no history of cardiovascular disease. Better IADL function is uniquely predicted by a body mass index less than 25 and no depression. Less ADL and IADL decline is predicted by better self-reported health, and less IADL decline is uniquely predicted by having no history of hip fracture after age 55., Conclusions: Maintaining or improving PF and preventing injury and disease in older adulthood (ages 65-80) has far-reaching implications for improving late-life (after age 80) functional independence., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The Women's Health Initiative has collected data on the aging process of postmenopausal women for over two decades, including data on many women who have achieved age 80 years and older. However, there has not been any previous effort to characterize the 80+ cohort and to identify associated retention factors., Methods: We include all women at baseline of the Women's Health Initiative who would be at least 80 years of age as of September 17, 2012. We summarize retention rates during the study and across two re-enrollment campaigns as well as the demographic and health-related characteristics that predicted retention. Further, we describe the longitudinal change from baseline in the women identified as members of the 80+ cohort., Results: Retention rates were lower during each of two re-enrollment periods (74% and 83% retained during re-enrollment periods 1 and 2, respectively) than during the first and second data collection periods (90% each). Women who were retained were more likely to be white, educated, and healthier at baseline. Women age 80 and older saw modest changes in body mass index and depression burden, despite lower physical activity and increased cardiovascular disease., Conclusions: The characteristics of women who were retained in the 80+ cohort differ in significant ways compared with their peers at baseline. Identifying the characteristics associated with attrition in older cohorts is important because aging and worsening health has a negative impact on study attrition. Strategies should be implemented to improve retention rates among less healthy older adults., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The number of older adults living to age 80 and older is increasing rapidly, particularly among women. Correlates of quality of life (QOL) in very advanced ages are not known. We examined the association of demographic, social-psychological, lifestyle, and physical health variables with global QOL in a Women's Health Initiative (WHI) cohort of women aged 80 and older., Methods: 26,299 WHI participants, who had completed a recent psychosocial and medical update, were included in these analyses. Global QOL was assessed by a single item, asking the women to rate their overall QOL on a scale from 0 to 10. Characteristics of the women were examined by the level of their transformed global QOL scores (≤50, 50-70, ≥70), and multiple regression was used to examine which demographic, social-psychological, lifestyle and health variables were independently associated with higher global QOL., Results: Social-psychological and current health variables were more strongly associated with global QOL than a history of selected comorbid conditions. In particular, higher self-rated health and fewer depressive symptoms were the most strongly associated with better global QOL in WHI women ≥80 years., Conclusions: Interventions to reduce depressive symptoms and improve health may lead to better self-reported health and global QOL among older women. Physical and mental health screenings followed by evidence-based interventions are imperative in geriatric care., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To investigate associations between proxy report of cognitive and functional limitations and cognitive performance and current or former driving status in older women with mild cognitive impairment (MCI) and all-cause dementia., Design: Cross-sectional data analysis of retrospectively identified older women with adjudicated MCI and all-cause dementia in the Women's Health Initiative Memory Study-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO)., Setting: Academic medical center., Participants: Women (mean age ± standard deviation 83.7 ± 3.5) adjudicated with MCI or dementia during Year 1, 2, 3, or 4 of the WHIMS-ECHO follow-up period (N = 385)., Measurements: The telephone-administered cognitive battery included tests of attention, verbal learning and memory, verbal fluency, executive function, working memory, and global cognitive function plus self-report measures of depressive symptomatology. The Dementia Questionnaire (DQ) was administered to a knowledgeable proxy (family member, friend)., Results: Sixty percent of women with MCI and 40% of those with dementia are current drivers. Proxy reports of functional limitations in instrumental activities of daily living (IADLs) are associated with current driving status in women with MCI, whereas performance-based cognitive tests are not. In women with dementia, proxy reports of functional limitations in IADLs and performance-based cognitive tests are associated with current driving status, as expected., Conclusion: These findings have clinical implications for the importance of evaluating driving concurrently with other instrumental functional abilities in MCI and dementia. Additional work is needed to determine whether proxy report of cognitive and functional impairments should help guide referrals for driving assessment and rehabilitation or counseling for driving transition., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Objectives: To determine whether smaller brain volumes in older women who had completed Women's Health Initiative (WHI)-assigned conjugated equine estrogen-based hormone therapy (HT), reported by WHI Memory Study (WHIMS)-MRI, correspond to a continuing increased rate of atrophy an average of 6.1 to 7.7 years later in WHIMS-MRI2., Methods: A total of 1,230 WHI participants were contacted: 797 (64.8%) consented, and 729 (59%) were rescanned an average of 4.7 years after the initial MRI scan. Mean annual rates of change in total brain volume, the primary outcome, and rates of change in ischemic lesion volumes, the secondary outcome, were compared between treatment groups using mixed-effect models with adjustment for trial, clinical site, age, intracranial volumes, and time between MRI measures., Results: Total brain volume decreased an average of 3.22 cm(3)/y in the active arm and 3.07 cm(3)/y in the placebo arm (p = 0.53). Total ischemic lesion volumes increased in both arms at a rate of 0.12 cm(3)/y (p = 0.88)., Conclusions: Conjugated equine estrogen-based postmenopausal HT, previously assigned at WHI baseline, did not affect rates of decline in brain volumes or increases in brain lesion volumes during the 4.7 years between the initial and follow-up WHIMS-MRI studies. Smaller frontal lobe volumes were observed as persistent group differences among women assigned to active HT compared with placebo. Women with a history of cardiovascular disease treated with active HT, compared with placebo, had higher rates of accumulation in white matter lesion volume and total brain lesion volume. Further study may elucidate mechanisms that explain these findings.

Importance: Postmenopausal hormone therapy with conjugated equine estrogens (CEEs) may adversely affect older women’s cognitive function. It is not known whether this extends to younger women., Objective: To test whether prescribing CEE-based hormone therapy to postmenopausal women aged 50 to 55 years has longer-term effects on cognitive function., Design: Trained, masked staff assessed participants with an annual telephone-administered cognitive battery that included measures of global and domain-specific cognitive functions. Cognitive testing was conducted an average of 7.2 years after the trials ended, when women had a mean age of 67.2 years, and repeated 1 year later. Enrollment occurred from 1996 through 1999., Setting: Forty academic research centers., Participants: The study population comprised 1326 postmenopausal women, who had begun treatment in 2 randomized placebo-controlled clinical trials of hormone therapy when aged 50 to 55 years., Intervention: The clinical trials in which the women had participated had compared 0.625 mg CEE with or without 2.5 mg medroxyprogesterone acetate over a mean of 7.0 years., Main Outcomes and Measures: The primary outcome was global cognitive function. Secondary outcomes were verbal memory, attention, executive function, verbal fluency, and working memory., Results: Global cognitive function scores from women who had been assigned to CEE-based therapies were similar to those from women assigned to placebo: mean (95% CI) intervention effect of 0.02 (−0.08 to 0.12) standard deviation units (P = .66). Similarly, no overall differences were found for any individual cognitive domain (all P > .15). Prespecified subgroup analyses found some evidence that CEE-based therapies may have adversely affected verbal fluency among women who had prior hysterectomy or prior use of hormone therapy: mean treatment effects of −0.17 (−0.33 to −0.02) and −0.25 (−0.42 to −0.08), respectively; however, this may be a chance finding., Conclusions and Relevance: CEE-based therapies produced no overall sustained benefit or risk to cognitive function when administered to postmenopausal women aged 50 to 55 years. We are not able to address whether initiating hormone therapy during menopause and maintaining therapy until any symptoms are passed affects cognitive function, either in the short or longer term., Trial Registration: clinicaltrials.gov Identifier: NCT01124773.