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BackgroundResearch has suggested optimism is associated with healthy aging and exceptional longevity, but most studies were conducted among non-Hispanic White populations. We examined associations of optimism to longevity across racial and ethnic groups and assessed healthy lifestyle as a possible mediating pathway.MethodsParticipants from the Women's Health Initiative (N = 159,255) completed a validated measure of optimism and provided other demographic and health data at baseline. We evaluated associations of optimism with increments in lifespan using accelerated failure time models, and with likelihood of exceptional longevity (survival to age ≥90) using Poisson regression models. Causal mediation analysis explored whether lifestyle-related factors mediated optimism-lifespan associations.ResultsAfter covariate adjustment, the highest versus lowest optimism quartile was associated with 5.4% (95% confidence interval [CI] = 4.5, 6.4%) longer lifespan. Within racial and ethnic subgroups, these estimates were 5.1% (95%CI = 4.0, 6.1%) in non-Hispanic White, 7.6% (95%CI = 3.6, 11.7%) in Black, 5.4% (95%CI = -0.1, 11.2%) in Hispanic/Latina, and 1.5% (95% CI = -5.0, 8.5) in Asian women. A high proportion (53%) of the women achieved exceptional longevity. Participants in the highest versus lowest optimism quartile had greater likelihood of achieving exceptional longevity (e.g., full sample risk ratio = 1.1, 95%CI = 1.1, 1.1). Lifestyle mediated 24% of the optimism-lifespan association in the full sample, 25% in non-Hispanic White, 10% in Black, 24% in Hispanic/Latina, and 43% in Asian women.ConclusionsHigher optimism was associated with longer lifespan and a greater likelihood of achieving exceptional longevity overall and across racial and ethnic groups. The contribution of lifestyle to these associations was modest. Optimism may promote health and longevity in diverse racial and ethnic groups. Future research should investigate these associations in less long-lived populations.

Purpose: Our goal was to evaluate vitamin D supplementation for preventing or treating overactive bladder and urinary incontinence in men. Materials and Methods: Ancillary study of men aged ≤55 years in VITAL (VITamin D and OmegA-3 TriaL). Randomized treatments included: vitamin D3 (cholecalciferol), marine omega-3 fatty acids, or matching placebo. Structured urinary incontinence questions measured the prevalence of overactive bladder at year 5 and urinary incontinence at years 2 and 5, along with incidence and progression of urinary incontinence from years 2 to 5. Prespecified subgroup analyses examined men with low baseline serum 25-hydroxyvitamin D (<20 ng/mL). Results: Among the 11,486 men who provided data at year 2 and 10,474 at year 5, mean age was 68 years at year 2, with 23% racial/ethnic minorities. In primary analyses, vitamin D supplementation compared to placebo did not lower odds of overactive bladder at year 5 (OR 0.97, 95% CI 0.87-1.08) or weekly urinary incontinence at year 2 (OR 0.94, 95% CI 0.83-1.05) or year 5 (OR 0.98, 95% CI 0.88-1.09). We found interactions of baseline serum 25-hydroxyvitamin D level with vitamin D supplementation for overactive bladder (P value for interaction = .001), and secondarily, for any urinary incontinence at year 2 (P value for interaction = .05). Men with baseline 25-hydroxyvitamin D <20 ng/mL, who were assigned to vitamin D supplements, had lower odds of overactive bladder (OR 0.51, 95% CI 0.35-0.76) compared to placebo, yet higher odds of any urinary incontinence (OR 1.24, 95% CI 0.93-1.64). Conclusions: Overall, vitamin D supplementation did not improve overactive bladder or urinary incontinence compared to placebo. However, specific use of vitamin D in men with lower 25-hydroxyvitamin D levels had inconsistent findings. [ABSTRACT FROM AUTHOR]

Background: Psychological factors (eg, depression) and related biological and behavioral responses are associated with numerous physical health outcomes. Most research in this area relies on self-reported assessments of psychological factors, which are difficult to scale because they may be expensive and time-consuming. Investigators are increasingly interested in using social media as a novel and convenient platform for obtaining information rapidly in large populations. Objective: We evaluated the feasibility of obtaining Facebook data from a large ongoing cohort study of midlife and older women, which may be used to assess psychological functioning efficiently with low cost. Methods: This study was conducted with participants in the Nurses' Health Study II (NHSII), which was initiated in 1989 with biennial follow-ups. Facebook does not share data readily; therefore, we developed procedures to enable women to download and transfer their Facebook data to cohort servers (for linkage with other study data they have provided). Since privacy is a critical concern when collecting individual-level data, we partnered with a third-party software developer, Digi.me, to enable participants to obtain their own Facebook data and to send it securely to our research team. In 2020, we invited a subset of the 18,519 NHSII participants (aged 56-73 years) via email to participate. Women were selected if they reported on the 2017-2018 questionnaire that they regularly posted on Facebook and were still active cohort participants. We included an exit survey for those who chose not to participate in order to gauge the reasons for nonparticipation. Results: We invited 309 women to participate. Few women signed the consent form (n=52), and only 3 used the Digi.me app to download and transfer their Facebook data. This low participation rate was observed despite modifying our protocol between waves of recruitment, including by (1) excluding active health care workers, who might be less available to participate due to the pandemic, (2) developing a Frequently Asked Questions factsheet to provide more information regarding the protocol, and (3) simplifying the instructions for using the Digi.me app. On our exit survey, the reasons most commonly reported for not participating were concerns regarding data privacy and hesitation sharing personal Facebook posts. The low participation rate suggests that obtaining individual-level Facebook data in a cohort of middle-aged and older women may be challenging. Conclusions: In this cohort of midlife and older women who were actively participating for over three decades, we were largely unable to obtain permission to access individual-level data from participants'Facebook accounts. Despite working with a third-party developer to customize an app to implement safeguards for privacy, data privacy remained a key concern in these women. Future studies aiming to leverage individual-level social media data should explore alternate populations or means of sharing social media data. [ABSTRACT FROM AUTHOR]

Background: The apolipoprotein E (APOE) e4 allele is a well-established genetic risk factor of brain aging. Vigorous physical activity may be particularly important in APOE-e4 carriers, but data have been inconsistent, likely due to differences in the timing of the physical activity assessment, definition of cognitive decline, and/or sample size.Methods: We prospectively evaluated the association between vigorous physical activity and cognition assessed at least 9 years later, according to APOE-e4 carrier status. Biennially from 1986, Nurses' Health Study participants reported their leisure-time physical activities. Starting in 1995-2001 and through 2008, participants (aged 70+ years) underwent up to 4 repeated cognitive telephone assessments (6 tasks averaged together using z-scores).Results: Among 7252 women, latent process mixed models identified 3 major patterns of cognitive change over 6 years: high-stable, medium-stable, and decline. Taking the high-stable cognitive trajectory as the outcome reference in multinomial logistic regressions, highest tertile of vigorous physical activity (≥5.9 metabolic-equivalent [MET]-hours/wk) compared to lowest tertile (≤0.9 MET-hours/wk) was significantly associated with subsequent lower likelihood of the medium-stable trajectory in the global score (odds ratio [OR] [95% CI] = 0.72 [0.63, 0.82]), verbal memory (OR [95% CI] = 0.78 [0.68-0.89]), and telephone interview of cognitive status score (OR [95% CI] = 0.81 [0.70-0.94]). Vigorous physical activity was also associated with lower likelihood of decline in category fluency (OR [95% CI] = 0.72 [0.56, 0.92]). We observed some evidence (p-interaction = .07 for the global score) that the association was stronger among APOE-e4 carriers than noncarriers (OR [95% CI] = 0.60 [0.39, 0.92] vs 0.82 [0.59, 1.16]).Conclusion: Midlife vigorous physical activity was associated with better cognitive trajectories in women in their seventies, with suggestions of stronger associations among APOE-e4 carriers. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES: Relatively little is known regarding predictors of advance care planning (ACP) in former nurses. We aimed to evaluate potential predictors of ACP documentation and discussion. DESIGN: Cross‐sectional study, 2012‐2014. SETTING: Nurses' Health Study. PARTICIPANTS: A total of 60,917 community‐dwelling female nurses aged 66 to 93 years living across the United States. MEASUREMENTS: Based on self‐reports, participants were categorized as having (1) only ACP documentation, (2) ACP documentation and a recent ACP discussion with a healthcare provider, or (3) neither. Multivariable log‐binomial models were used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) of the two separate ACP categories vs those with neither. We evaluated various demographic, health, and social factors. RESULTS: The large majority (84%) reported ACP documentation; 35% reported a recent ACP discussion. Demographic factors such as age and race were associated with both ACP categories. In multivariable analyses, race was most strongly associated: compared with whites, African Americans were 27% less likely (PR = 0.73; 95% CI = 0.69‐0.78) to report ACP documentation alone and 41% (PR = 0.59; 95% CI = 0.54‐0.66) less likely to report documentation with discussion. Additionally, health/healthcare‐related characteristics were more strongly associated with ACP documentation plus discussion. Women with functional limitations (PR = 1.15; 95% CI = 1.10‐1.20), women who were recently hospitalized (PR: 1.10; 95% CI = 1.08‐1.12) or women who had seen a physician for health symptoms (PR = 1.43; 95% CI = 1.35‐1.52) or screening (PR = 1.40; 95% CI = 1.32‐1.49) were more likely to report having both ACP documentation and discussion. Social factors showed limited relationships with ACP documentation only; for documentation plus discussion, being widowed and living alone was associated with higher prevalence (PR = 1.21; 95% CI = 1.19‐1.24) and having little emotional support was associated with lower prevalence (PR = 0.84; 95% CI = 0.81‐0.86). CONCLUSIONS: Among older nurses, most of whom reported having documented ACP, 35% reported recent patient‐clinician ACP discussions, indicating a major participatory gap in an element critical to ACP effectiveness. Even in nurses, African Americans reported less ACP documentation or discussion. J Am Geriatr Soc 67:292–301, 2019. [ABSTRACT FROM AUTHOR]

Benefits of a Mediterranean diet for cognition have been suggested, but epidemiologic studies have been relatively small and of limited duration. To prospectively assess the association between long-term adherence to a Mediterranean dietary pattern and self-reported subjective cognitive function (SCF). Prospective observational study. The Health Professionals’ Follow-up Study, a prospective cohort of 51,529 men, 40-75 years of age when enrolled in 1986, of whom 27,842 were included in the primary analysis. Mediterranean diet (MD) score, computed from the mean of five food frequency questionnaires, assessed every 4 years from 1986 to 2002. Self-reported SCF assessed by a 6-item questionnaire in 2008 and 2012, and validated by association with genetic variants in apolipoprotein-4. Using the average of 2008 and 2012 SCF scores, 38.0% of men were considered to have moderate memory scores and 7.3% were considered to have poor scores. In a multivariate model, compared with men having a MD score in the lowest quintile, those in the highest quintile had a 36% lower odds of a poor SCF score (odds ratio 0.64, 95% CI 0.55-0.75; P, trend < 0.001) and a 24% lower odds of a moderate SCF score (OR 0.76, 95% CI 0.70-0.83; P, trend < 0.001). Both remote and more recent diet contributed to this relation. Associations were only slightly weaker using baseline dietary data and a lag of 22 years. Long-term adherence to the Mediterranean diet pattern was strongly related to lower subjective cognitive function. These findings provide further evidence that a healthy dietary pattern may prevent or delay cognitive decline. [ABSTRACT FROM AUTHOR]

Aim: To examine the association between a healthy diet, assessed by the Healthy Diet Indicator (HDI), and cognitive decline in older adults. Methods: Data from 21,837 participants aged ≥ 55 years from 3 cohorts (Survey in Europe on Nutrition and the Elderly, a Concerted Action [SENECA], Rotterdam Study [RS], Nurses' Health Study [NHS]) were analyzed. HDI scores were based on intakes of saturated fatty acids, polyunsaturated fatty acids, mono- and disaccharides, protein, cholesterol, fruits and vegetables, and fiber. The Telephone Interview for Cognitive Status in NHS and Mini-Mental State Examination in RS and SENECA were used to assess cognitive function from multiple repeated measures. Using multivariable-adjusted, mixed linear regression, mean differences in annual rates of cognitive decline by HDI quintiles were estimated. Results: Multivariable-adjusted differences in rates in the highest versus the lowest HDI quintile were 0.01 (95% CI -0.01, 0.02) in NHS, 0.00 (95% CI -0.02, 0.01) in RS, and 0.00 (95% CI -0.05, 0.05) in SENECA with a pooled estimate of 0.00 (95% CI -0.01, 0.01), I² = 0%. Conclusions: A higher HDI score was not related to reduced rates of cognitive decline in European and American older adults. [ABSTRACT FROM AUTHOR]

Previous studies suggest that hormonal factors modulate the natural course of psoriasis in women. However, the association of hormonal factors with psoriasis risk has not been assessed using prospective data. We carried out a thorough prospective analysis on the topic in 163,763 women in the Nurses' Health Study I and II. Participants provided information on age at menarche, parity, menopause status, and exogenous hormone use (oral contraceptive and postmenopausal hormone therapy) over the follow-up. We ascertained 1,253 incident psoriasis cases over 2 million person-years. Psoriasis risk appeared to be higher in women with always irregular menstrual cycles in adulthood (multivariate-adjusted hazard ratio = 1.32, 95% confidence interval (CI): 1.01-1.73, compared with regular cycles) and surgical menopause (hazard ratio=1.19, 95% CI: 1.01-1.40, compared with natural menopause). Hormone therapy had suggestive but insignificant associations with psoriasis risk. Our results suggest little evidence for hormonal factors and risk of psoriasis in women that need further investigation. [ABSTRACT FROM AUTHOR]

ABSTRACT The role of fruit and vegetable intake in relation to fracture prevention during adulthood and beyond is not adequately understood. We investigated the potential association between fruit and vegetable intake and hip fracture incidence in a large sample of older adults from Europe and the United States. A total of 142,018 individuals (116,509 women) aged ≥60 years, from five cohorts, were followed up prospectively for 1,911,482 person-years, accumulating 5552 hip fractures. Fruit and vegetable intake was assessed by validated, cohort-specific, food-frequency questionnaires (FFQ). Ηip fractures were ascertained through national patient registers or telephone interviews/questionnaires. Adjusted hazard ratios (HRs) derived by Cox proportional hazards regression were estimated for each cohort and subsequently pooled using random effects meta-analysis. Intake of ≤1 serving/day of fruit and vegetables combined was associated with 39% higher hip fracture risk (pooled adjusted HR, 1.39; 95% confidence interval [CI], 1.20 to 1.58) in comparison with moderate intake (>3 and ≤5 servings/day) ( pfor heterogeneity = 0.505), whereas higher intakes (>5 servings/day) were not associated with lower risk in comparison with the same reference. Associations were more evident among women. We concluded that a daily intake of 1 or <1 servings of fruits and vegetables was associated with increased hip fracture risk in relation to moderate daily intakes. Older adults with such low fruit and vegetable consumption may benefit from raising their intakes to moderate amounts in order to reduce their hip fracture risk. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

To investigate whether a positive transition into retirement may be associated with later cognitive aging, we included a subset of 4,926 Nurses' Health Study participants who retired from work at ages 60-69, then provided a subjective assessment of the change in overall quality of life (QOL) with retirement. Subsequently (range: 1 month to 4.7 years later), when all were aged 70+ years, they completed a baseline telephone cognitive battery evaluating global cognition, episodic memory, and executive function. They had up to three follow-up cognitive assessments. Controlling for various occupational factors before retirement and socioeconomic, lifestyle, and health-related factors as of the baseline cognitive assessment, we used generalized linear models for repeated measures to estimate mean differences in rates of cognitive decline across categories of QOL transition at retirement: "worse", "same", or "better". Over a median 6 years of follow-up, the global cognitive score change was -0.123 on average. Compared with women who reported no change in QOL at retirement (31%), women who reported improvement (61%) showed a significantly slower rate of cognitive decline (difference = +0.011 95% CI = 0.004, 0.019). This mean difference was equivalent to that observed between women who were 2 years apart in age. No significant differences in cognitive decline rates were observed for the women who reported worsened QOL (8%). Secondary analyses to address possible reverse causation showed robust associations. A positive transition into retirement was associated with better maintenance of cognitive function over time in aging women. These findings need to be replicated in other populations. [ABSTRACT FROM AUTHOR]

Background: Physical function is integral to healthy aging, in particular as a core component of mobility and independent living in older adults, and is a strong predictor of mortality. Limited research has examined the role of diet, which may be an important strategy to prevent or delay a decline in physical function with aging.Objective: We prospectively examined the association between the Alternative Healthy Eating Index-2010 (AHEI-2010), a measure of diet quality, with incident impairment in physical function among 54,762 women from the Nurses' Health Study.Methods: Physical function was measured by the Medical Outcomes Short Form-36 (SF-36) physical function scale and was administered every 4 y from 1992 to 2008. Cumulative average diet was assessed using food frequency questionnaires, administered approximately every 4 y. We used multivariable Cox proportional hazards models to estimate the HRs of incident impairment of physical function.Results: Participants in higher quintiles of the AHEI-2010, indicating a healthier diet, were less likely to have incident physical impairment than were participants in lower quintiles (P-trend < 0.001). The multivariable-adjusted HR of physical impairment for those in the top compared with those in the bottom quintile of the AHEI-2010 was 0.87 (95% CI: 0.84, 0.90). For individual AHEI-2010 components, higher intake of vegetables (P-trend = 0.003) and fruits (P-trend = 0.02); lower intake of sugar-sweetened beverages (P-trend < 0.001), trans fats (P-trend = 0.03), and sodium (P-trend < 0.001); and moderate alcohol intake (P-trend < 0.001) were each significantly associated with reduced rates of incident physical impairment. Among top contributors to the food components of the AHEI-2010, the strongest relations were found for increased intake of oranges, orange juice, apples and pears, romaine or leaf lettuce, and walnuts. However, associations with each component and with specific foods were generally weaker than the overall score, indicating that overall diet pattern is more important than individual parts.Conclusions: In this large cohort of older women, a healthier diet was associated with a lower risk of developing impairments in physical function. [ABSTRACT FROM AUTHOR]

Context: Increasing evidence suggests that circadian and sleep parameters influence cognitive function with aging. Objective: To evaluate observational studies of sleep duration and cognition in older adults. Data Sources: A systematic review of OVID Medline and PsycINFO through September 2015, and review of bibliographies from studies identified. Study Selection: English-language articles reporting observational studies of sleep duration and cognitive function in older populations. Data Extraction: Data extraction by 2 authors using predefined categories of desired information. Results: Thirty-two studies met our inclusion criteria, with nearly two-thirds published in the past 4 years. One-third of studies indicated that extreme sleep durations were associated with worse cognition in older adults. More studies favored an association with long vs. short sleep durations (35 vs. 26% of studies, respectively). Four studies found that greater changes in sleep duration over time were related to lower cognition. Study design and analytic methods were very heterogeneous across studies; therefore, meta-analysis was not undertaken. Limitations: We reviewed English-language manuscripts only, with a qualitative summary of studies identified. Conclusions and Implications of Key Findings: Observational studies of sleep duration and cognitive function in older adults have produced mixed results, with more studies suggesting that long (rather than short) sleep durations are related to worse cognition. Studies more consistently indicate that greater changes in sleep duration are associated with poor cognition. Future studies should be prospectively designed, with objective sleep assessment and longer follow-up periods; intervention studies are also needed to identify strategies for promoting cognitive health with aging. © 2016 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to assess the utility of the Cogstate self-administered computerized neuropsychological battery in a large population of older men. Methods: We invited 7,167 men (mean age of 75 years) from the Health Professionals Follow-up Study, a prospective cohort of male health professionals. We considered individual Cogstate scores and composite scores measuring psychomotor speed and attention, learning and working memory and overall cognition. Multivariate linear regression was used to assess the association between risk factors measured 4 and 28 years prior to cognitive testing and each outcome. Results: The 1,866 men who agreed to complete Cogstate testing were similar to the 5,301 non-responders. Many expected risk factors were associated with Cogstate scores in multivariate adjusted models. Increasing age was significantly associated with worse performance on all outcomes (p < 0.001). For risk factors measured 4 years prior to testing and overall cognition, a history of hypertension was significantly associated with worse performance (mean difference of -0.08 standard units (95% CI -0.16, 0.00)) and higher consumption of nuts was significantly associated with better performance (>2 servings/week vs. <1 serving/month: 0.15 (0.03, 0.27)). Conclusions: The self-administered Cogstate battery showed significant associations with several risk factors known to be associated with cognitive function. Future studies of cognitive aging may benefit from the numerous advantages of self-administered computerized testing. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective To evaluate the association between infertility and fertility treatments on subsequent risk of hypertension. Design Cohort study. Setting Not applicable. Patient(s) A total of 116,430 female nurses, followed from 1993 to June 2011, as part of the Nurses' Health Study II cohort. Intervention(s) None. Main Outcome Measure(s) Self-reported, physician-diagnosed hypertension. Result(s) Compared with women who have never reported infertility, infertile women were at no greater risk of hypertension (multivariable adjusted relative risk (RR) = 1.01, with 95% confidence interval [CI] [0.94–1.07]). Infertility due to tubal disease was associated with a higher risk of hypertension (RR = 1.15 [1.01–1.31]), but no other diagnoses were associated with hypertension risk, compared with women who did not report infertility (ovulatory disorder: RR = 1.03 [0.94–1.13]; cervical: RR = 0.88 [0.70–1.10]; male factor: RR = 1.05 [0.95–1.15]; other reason: RR = 1.02 [0.94–1.11]; reason not found: RR = 1.02 [0.95–1.10]). Infertile women collectively had 5,070 cases of hypertension. No clear pattern between use of fertility treatment and hypertension was found among infertile women (clomiphene citrate: RR = 0.97 [0.90–1.04]; gonadotropin alone: RR = 0.97 [0.87–1.08]; intrauterine insemination: RR = 0.86 [0.71–1.03]; in vitro fertilization: RR = 0.86 [0.73–1.01]). Conclusion(s) Among this relatively young cohort of women, no apparent increase occurred in hypertension risk among infertile women, or among women who had undergone fertility treatment previously. [ABSTRACT FROM AUTHOR]

Background. Microvascular and macrovascular abnormalities are frequently found on noninvasive tests performed in older adults. Their prognostic implications on disability and life expectancy have not been collectively assessed. Methods. This prospective study included 2,452 adults (mean age: 79.5 years) with available measures of microvascular (brain, retina, kidney) and macrovascular abnormalities (brain, carotid, coronary, peripheral artery) in the Cardiovascular Health Study. The burden of microvascular and macrovascular abnormalities was examined in relation to total, activity-of-daily-living disability-free, and severe disability-free life expectancies in the next 10 years (1999–2009). Results. At 75 years, individuals with low burden of both abnormalities lived, on average, 8.71 years (95% confidence interval: 8.29, 9.12) of which 7.67 years (7.16, 8.17) were without disability. In comparison, individuals with high burden of both abnormalities had shortest total life expectancy (6.95 years [6.52, 7.37]; p < .001) and disability-free life expectancy (5.60 years [5.10, 6.11]; p < .001). Although total life expectancy was similarly reduced for those with high burden of either type of abnormalities (microvascular: 7.96 years [7.50, 8.42] vs macrovascular: 8.25 years [7.80, 8.70]; p = .10), microvascular abnormalities seemed to have larger impact than macrovascular abnormalities on disability-free life expectancy (6.45 years [5.90, 6.99] vs 6.96 years [6.43, 7.48]; p = .016). These results were consistent for severe disability-free life expectancy and in individuals without clinical cardiovascular disease. Conclusions. Considering both microvascular and macrovascular abnormalities from multiple noninvasive tests may provide additional prognostic information on how older adults spend their remaining life. Optimal clinical use of this information remains to be determined. [ABSTRACT FROM PUBLISHER]

Background: Observational studies among older women have associated vitamin D insufficiency with a greater prevalence and incidence of urinary incontinence. However, little is known about the effect of vitamin D supplementation in reducing urinary incontinence.Objective: This study aimed to evaluate the effects of vitamin D supplementation in reducing the frequency of urinary incontinence in older women.Study Design: We conducted an ancillary study of women aged ≥55 years in the Vitamin D and Omega-3 Trial, a randomized trial with a 2×2 factorial design. Recruitment of participants started from 2011 to 2014 across 50 US states, and the follow-up of participants ended in January 2018. Randomized treatments in the parent study included (1) vitamin D3 (cholecalciferol) at a dosage of 2000 IU/d, (2) marine omega-3 fatty acids at a dosage of 1 g/d, and (3) matching placebo. Here, we analyzed women according to their randomization to vitamin D supplementation or placebo, regardless of treatment with omega-3 fatty acid supplementation. Validated frequency of urinary incontinence questions were added in year 2 of the study and were used again in year 5 at the end of trial. Prespecified ancillary outcomes included the prevalence of urinary incontinence at years 2 and 5, along with incident incontinence and progression of incontinence (from lower to higher frequency) from year 2 to year 5. Preplanned subgroup analyses examined the following outcomes: prerandomization of low serum levels of vitamin D (serum 25-hydroxyvitamin D<20 ng/mL), incontinence types, weight categories, and African American race.Results: Among the randomized women who provided urinary incontinence data, 11,646 women at year 2 and 10,527 women at year 5, the mean age was 70 years at year 2, with 29% racial and ethnic minorities. The prevalence of urinary incontinence that occurred at least weekly was 29% at year 2 and increased to 37% at year 5. Vitamin D supplementation compared to with placebo was not associated with lower odds of urinary incontinence occurring at least weekly at year 2 (odds ratio, 1.08; 95% confidence interval, 0.99-1.19) or year 5 (odds ratio, 1.04; 95% confidence interval, 0.94-1.15). Vitamin D supplementation compared to placebo was not associated with lower incidence or progression of urinary incontinence from year 2 to year 5: incidence (odds ratio, 1.06; 95% confidence interval, 0.83-1.35) or progression (odds ratio, 0.94; 95% confidence interval, 0.82-1.08). Women with prerandomization of low serum levels of vitamin D (n=836) did not have lower odds of the prevalence, incidence, or progression of urinary incontinence. The findings were null in subgroups according to incontinence type, women with obesity, and African American women. Only women with healthy weight randomized to vitamin D had lower odds of progression of urinary incontinence (odds ratio, 0.78; 95% confidence interval, 0.63-0.95; P=.01).Conclusion: Vitamin D supplementation compared to placebo for 2 to 5 years was not associated with differences in the prevalence, incidence, or progression of urinary incontinence in older women with and without adequate serum vitamin D levels, with inconsistent differences among subgroups. The findings showed that the broad use of moderate doses of vitamin D supplementation did not reduce urinary incontinence in older women. [ABSTRACT FROM AUTHOR]

Objectives To evaluate associations between sleep duration at midlife and later life and change in sleep duration over time and cognition in older women. Design Participants reported sleep duration in 1986 and 2000, and a subgroup of older participants began cognitive testing in 1995 to 2001; follow-up testing was conducted three times, at 2-year intervals. Setting Prospective Nurses' Health Study cohort. Participants Female nurses aged 70 and older free of stroke and depression at the initial cognitive assessment (N = 15,385). Measurements Validated, telephone-based cognitive battery to measure cognitive function; four repeated assessments over 6 years were averaged to estimate overall cognition at older ages, and trajectories of cognitive change were evaluated over follow up. Results Extreme sleep durations in later life were associated with worse average cognition ( P < .001 for the quadratic term for a global score averaging all six cognitive tests). For example, women sleeping 5 h/d or less had worse global cognition than those sleeping 7 h/d, as did women sleeping 9 h/d or more; differences were equivalent to nearly 2 additional years of age. Associations were similar, although slightly attenuated, for sleep duration in midlife. Women whose sleep duration changed by 2 h/d or more over time had worse cognition than women with no change in sleep duration (e.g., for the global score, P < .001 for the quadratic term). Sleep duration was not associated with trajectories of cognitive function over 6 years, which might be attributable to short follow-up for detecting cognitive decline. Conclusion Extreme sleep durations at midlife and later life and extreme changes in sleep duration over time appear to be associated with poor cognition in older women. [ABSTRACT FROM AUTHOR]

The article describes a cohort study of the association between phobic anxiety and cognitive function in older community-living women. Subjects who had been diagnosed with phobic anxiety for 10 years were assessed for cognitive abilities such as word memory, category fluency, and working memory over approximately 4.4. years. The results indicate links between phobic anxiety severity and overall cognitive function and verbal memory, but suggest the cognitive changes occurred in mid-life.

Background: Seafood consumption may prevent age-related cognitive decline. However, benefits may vary by nutrient contents in different seafood types. We examined associations between total seafood consumption and cognitive decline and whether these associations differ by seafood types.Methods: We conducted a prospective cohort study of 5,988 women (mean age, 72 years) from the Women's Health Study who self-reported seafood intake at Women's Health Study baseline and also participated in telephone assessments of general cognition, verbal memory, and category fluency administered 5.6 years after Women's Health Study baseline and 2 and 4 years thereafter. Primary outcomes were standardized composite scores of global cognition and verbal memory.Results: After adjusting for potential confounders, different amounts of total seafood consumption were not associated with changes in global cognition (p = .56) or verbal memory (p = .29). Considering seafood types, however, compared with women consuming less than once-weekly tuna or dark-meat finfish, those with once-weekly or higher consumption had significantly better verbal memory (0.079 standard units; p < .01) after 4 years-a difference comparable to that for women 2.1 years apart in age. There was also a statistically nonsignificant suggestion of better global cognition (p = .13) with once-weekly or higher tuna or dark-meat fish consumption. No significant associations were observed for light-meat finfish or shellfish.Conclusions: The relation of seafood to cognition may depend on the types consumed. Total consumption levels of seafood were unrelated to cognitive change. However, consumption of tuna and dark-meat fish once weekly or higher was associated with lower decline in verbal memory for a period of 4 years. [ABSTRACT FROM AUTHOR]

In this large-scale prospective epidemiological study, we examined associations of long-term adherence to the Mediterranean diet (MeDi) and subsequent cognitive function and decline. We included 16,058 women from the Nurses' Health Study, aged ->70 y, who underwent cognitive testing by telephone 4 times during 6 y, beginning in 1995-2001, and provided repeated information on diet between 1984 and the first cognitive exam. Primary outcomes were the Telephone Interview for Cognitive Status (TICS) and composite scores of verbal memory and global cognition. MeDi adherence was based on intakes of: vegetables, fruits, legumes, whole grains, nuts, fish, red and processed meats, moderate alcohol, and the ratio of monounsaturated:saturated fat. Long-term MeDi exposure was estimated by averaging all repeated measures of diet (>13 y, on average). In primary analyses of cognitive change, the MeDi was not associated with decline in global cognition or verbal memory. In a secondary approach examining cognitive status in older age, determined by averaging all 4 repeated measures of cognition, each higher quintile of long-term MeDi score was linearly associated with better multivariable-adjusted mean cognitive scores [differences in mean Z-scores between extreme quintiles of MeDi = 0.06 (95% CI: 0.01, 0.11); = 0.05 (95% CI: 0.01, 0.08); and = 0.06 (95% CI: 0.03, 0.10) standard units; P-trends = 0.004, 0.002, and <0.001 for TICS, global cognition, and verbal memory, respectively]. These associations were similar to those observed in women 1-1.5 y apart in age. In summary, long-term MeDi adherence was related to moderately better cognition but not with cognitive change in this very large cohort of older women. [ABSTRACT FROM AUTHOR]

The authors examined long-term antioxidant intake in relation to cognitive decline among older women. Beginning in 1980, Nurses’ Health Study (NHS) participants completed dietary assessments every 4 years; in 1995–2001, 16,010 participants aged ≥70 years completed initial cognitive assessments, which were repeated 3 times at 2-year intervals. Long-term antioxidant intake was averaged from 1980 through the time of initial cognitive interviews. Multivariable-adjusted linear regression was used to estimate mean differences in rates of cognitive decline across categories of vitamin E, vitamin C, and carotenoid intake; statistical tests were 2-sided. No associations were evident for vitamin E or total carotenoid intake and cognitive decline (e.g., after multivariable adjustment, P-trend = 0.44 and P-trend = 0.51, respectively, for a global composite score averaging all 6 cognitive tests), although higher lycopene intake and lower vitamin C intake were related to slower cognitive decline. In alternative analyses of overall cognitive status at older ages (averaging all 4 cognitive assessments), results for vitamins E and C were generally null, but higher carotenoid intake was related to better cognition. Overall, long-term vitamin E and C intakes were not consistently related to cognition, although greater consumption of carotenoids may have cognitive benefits in older adults. [ABSTRACT FROM PUBLISHER]

Purpose: Little research has been conducted on the epidemiology of urinary incontinence in individuals with type 2 diabetes. We examined prevalence, incidence and risk factors for urinary incontinence among women with type 2 diabetes in the NHS (Nurses'' Health Study) and NHS II. Materials and Methods: We obtained urinary incontinence information at study baseline (2000 in NHS and 2001 in NHS II) and 2 followup periods (2002 and 2004 in the NHS, and 2003 and 2005 in the NHS II). Among women with type 2 diabetes we calculated the prevalence of urinary incontinence for 9,994 women with baseline urinary incontinence information, and urinary incontinence incidence rates for 4,331 women with no urinary incontinence at baseline and urinary incontinence information during followup. Multivariable adjusted odds ratios and relative risks were estimated for associations between possible risk factors and urinary incontinence. Results: The prevalence of at least monthly urinary incontinence was 48% and at least weekly urinary incontinence was 29% among women with type 2 diabetes, and the corresponding incidence rates were 9.1 and 3.4 per 100 person-years, respectively. White race, higher body mass index, higher parity, lower physical activity, current postmenopausal hormone use and diuretic use were risk factors for prevalent and incident urinary incontinence in this study, and hysterectomy, vascular disease and longer duration of diabetes were associated with increased odds of prevalent urinary incontinence only. Increasing age and microvascular complications were associated with a greater risk of frequent urinary incontinence. Conclusions: Urinary incontinence was common in this study of women with type 2 diabetes. We identified multiple risk factors for urinary incontinence in these women, several of which suggest ways to reduce urinary incontinence. [Copyright &y& Elsevier]

The article presents a population-based study that investigates the factors associated with soluble amyloid beta peptide concentrations in humans at late midlife. It states that linear regression was used to calculate age-adjusted mean differences by insulin and insulin-related factors. It reveals that insulin-related factors appear associated with lower plasma at late midlife.

OBJECTIVES: To examine the association between the type and number of subjective memory complaints (SMCs) and performance on objective cognitive tests. DESIGN: Cross-sectional. SETTING: Nurses' Health Study. PARTICIPANTS: Sixteen thousand nine hundred sixty-four women (mean age 74) who provided information on SMCs. MEASUREMENTS: Telephone cognitive assessments and seven questions regarding SMCs were administered. Cognitive impairment was defined as a score of less than 31 on the Telephone Interview for Cognitive Status (TICS) and below the 10th percentile on other cognitive measures. To assess associations with SMCs, multivariable logistic regression was used to calculate odds ratios for cognitive impairment and multivariable linear regression to calculate mean differences in cognitive test scores, adjusting for age and depressive symptoms. RESULTS: Some SMCs, such as trouble following a group conversation or finding one's way around familiar streets, were more highly associated than others with odds of cognitive impairment. The complaint of forgetting things from one second to the next, generally considered part of normal aging, was not associated with cognitive impairment. In addition, there were strong, linear trends of increasingly worse scores on cognitive tests with increasing numbers of memory complaints. For each additional SMC endorsed, the odds of cognitive impairment increased approximately 20% when each SMC was weighted equally. CONCLUSION: SMCs are associated with objective cognitive status and may be considered by primary care physicians in determining whether follow-up is warranted. [ABSTRACT FROM AUTHOR]

Purpose: Although caffeine consumption is common and generally believed to affect bladder function, little is known about caffeine intake and incident urinary incontinence. Materials and Methods: We performed a prospective cohort study in 65,176 women 37 to 79 years old without incontinence in the Nurses'' Health Study and the Nurses'' Health Study II. Incident incontinence was identified from questionnaires during 4 years of followup. Caffeine intake was measured using food frequency questionnaires administered before incontinence development. The multivariate adjusted relative risk of the relation between caffeine intake and incontinence risk as well as attributable risk were calculated. Results: Caffeine was not associated with incontinence monthly or more. However, there was a modest, significantly increased risk of incontinence at least weekly in women with the highest (greater than 450 mg) vs the lowest (less than 150 mg) daily intake (RR 1.19, 95% CI 1.06–1.34) and a significant trend of increasing risk with increasing intake (p for trend = 0.01). This risk appeared focused on incident urgency incontinence (greater than 450 vs less than 150 mg daily, RR 1.34, 95% CI 1.00–1.80, p for trend = 0.05) but not on stress or mixed incontinence (p for trend = 0.75 and 0.19, respectively). The attributable risk of urgency incontinence associated with high caffeine intake was 25%. Conclusions: Findings suggest that high but not lower caffeine intake is associated with a modest increase in the incidence of frequent urgency incontinence. A fourth of the cases with the highest caffeine consumption would be eliminated if high caffeine intake were eliminated. Confirmation of these findings in other studies is needed before recommendations can be made. [Copyright &y& Elsevier]

Purpose: Recent data in postmenopausal women indicate that current and past use of exogenous hormones is related to urinary incontinence risk. Little is known about exogenous hormones and risk of urinary incontinence in younger women. We investigated the association between oral contraceptive pills and incident urinary incontinence in premenopausal women enrolled in the Nurses'' Health Study II. Materials and Methods: Participants reported use of oral contraceptive pills from 1989 to 2001. Among 21,864 premenopausal women 37 to 54 years old reporting no urinary incontinence in 2001 we identified 749 with incident urinary incontinence at least weekly between 2001 and 2003. Odds ratios and 95% confidence intervals were estimated using multivariable logistic regression. Results: Women who had ever used oral contraceptive pills had a statistically significant 27% (95% CI 1–59) increased odds of experiencing urinary incontinence at least weekly compared with those who never used oral contraceptive pills. In women with 10 or more years of use the odds ratio increased to 1.48 (95% CI 1.13–1.95). Ever using oral contraceptive pills was specifically associated with urgency urinary incontinence (OR 2.48, 95% CI 1.07–5.76) rather than stress urinary incontinence (OR 1.04, 95% CI 0.78–1.40). Although we had limited information on urinary tract infection, control for urinary tract infection did not alter these findings. Conclusions: Use of oral contraceptive pills may be associated with a modest increase in the odds of urinary incontinence among premenopausal women. However, this is one of the first reports of such an association and, thus, further research is needed to confirm our findings and investigate possible mechanisms. [Copyright &y& Elsevier]

Purpose: To improve the understanding of the etiological relation between type 2 diabetes and urinary incontinence, we examined associations between diabetes and urinary incontinence type in 71,650 women 37 to 79 years old in the Nurses'' Health Study and the Nurses'' Health Study II. Materials and Methods: From 1976 to 2000 in the Nurses'' Health Study and 1989 to 2001 in the Nurses'' Health Study II participants reported diagnoses of type 2 diabetes. Women with incident urinary incontinence at least weekly were identified from 2000 to 2002 in the Nurses'' Health Study and 2001 to 2003 in the Nurses'' Health Study II. We pooled data from the 2 cohorts, and estimated odds ratios and 95% confidence intervals using multivariable logistic regression adjusting for age, parity, body mass index, smoking, hysterectomy, functional limitations, menopausal status, postmenopausal hormone use, incontinence promoting medications and study cohort. Results: The incidence of at least weekly urinary incontinence was 5.3% (3,612 of 67,984) among women without type 2 diabetes and 8.7% (318 of 3,666) among women with diabetes. Overall the multivariable adjusted odds of incident urinary incontinence were increased 20% (OR 1.2, 95% CI 1.0–1.3, p = 0.01) among women with vs without type 2 diabetes. This increase appeared largely explained by significantly greater odds of urge urinary incontinence (OR 1.4, 95% CI 1.0–1.9, p = 0.03). There was no apparent association between diabetes and stress (p = 0.3) or mixed (p = 0.6) urinary incontinence, although confidence intervals were somewhat wide. Conclusions: Our findings suggest that type 2 diabetes may especially influence urge urinary incontinence. Further research is needed to confirm this finding and identify pathways linking these conditions. [Copyright &y& Elsevier]

Purpose: While strenuous, high impact activity may provoke urinary incontinence, little is known about relations with moderate physical activity. We examined recreational activity and incident urinary incontinence in middle-aged women. Materials and Methods: This is a prospective study of women 37 to 54 years old in the Nurses’ Health Study II. Repeated physical activity reports from 1989 to 2001 were averaged to estimate long-term activity levels. From 2001 to 2003 we identified 4,081 incident cases with at least monthly urinary incontinence. Incontinence type was further determined among cases with at least weekly urinary incontinence. Multivariable logistic regression models were used to estimate adjusted relative risks of urinary incontinence across quantiles of physical activity. To determine whether relations were mediated by body mass index, separate models were constructed that excluded and included body mass index as a covariate. Results: The risk of at least monthly urinary incontinence decreased with increasing quintiles of moderate physical activity (RR 0.80, 95% CI 0.72–0.89 comparing extreme quintiles). For stress and urge urinary incontinence, women with the most physical activity had lower rates of incontinence than those with less activity. RRs were 0.75 (95% CI 0.59–0.96 for top vs bottom quartile) for stress urinary incontinence and 0.53 (95% CI 0.31–0.90) for urge urinary incontinence. After adjustment for body mass index, the overall association with at least monthly incontinence attenuated, but remained significant (RR 0.89, 95% CI 0.80–0.99 comparing extreme quintiles). Conclusions: Long-term, moderate physical activity was inversely associated with urinary incontinence. The role of exercise in weight maintenance may partly explain this association. [Copyright &y& Elsevier]

Objective: The purpose of this study was to identify risk factors for urinary incontinence in middle-aged women. Study design: We conducted a cross-sectional analysis of 83,355 Nurses' Health Study II participants. Since 1989, women have provided health information on mailed questionnaires; in 2001, at the ages 37 to 54 years, information on urinary incontinence was requested. We examined adjusted odds ratios of incontinence using logistic regression. Results: Forty-three percent of the women reported incontinence. After adjustment, black (odds ratio, 0.49; 95% CI, 0.40–0.60) and Asian-American women (odds ratio, 0.57; 95% CI, 0.46–0.72) were at reduced odds of severe incontinence compared with white women. Increased age, body mass index, parity, current smoking, type 2 diabetes mellitus, and hysterectomy all were associated positively with incontinence. Women who were aged 50 to 54 years had 1.81 times the odds of severe incontinence compared with women who were < 40 years old (95% CI, 1.66–1.97); women with a body mass index of ≥30 kg/m² had 3.10 times the odds of severe incontinence compared with a body mass index of 22 to 24 kg/m² (95% CI, 2.91–3.30). Conclusion-Urinary incontinence is highly prevalent among these middle-aged women. Potential risk factors include age, race/ethnicity, body mass index, parity, smoking, diabetes mellitus, and hysterectomy. [ABSTRACT FROM AUTHOR]

Background: Experimental data suggest that oxygen free radicals are probably involved in the deterioration of cognitive processes. Objective: Our objective was to investigate the relation of highdose antioxidant supplements to cognition. Design: Information on the use of specific supplements containing vitamins E and C was collected biennially via mailed questionnaires beginning in 1980 from 14 968 community-dwelling women who participated in the Nurses' Health Study. From 1995 to 2000, telephone tests of cognitive function [Telephone Interview of Cognitive Status (TICS), delayed recall of the TICS 10-word list, immediate and delayed recall of a short paragraph, a test of verbal fluency, and a digit span backwards test] were administered to the women, who were 70-79 y of age at that time. We used linear and logistic regression models to calculate multivariateadjusted mean differences in test scores and relative risks of a low score for specific supplement users compared with nonusers. Results: Long-term, current users of vitamin E with vitamin C had significantly better mean performance, as judged by a global score that combined individual test scores, than did women who had never used vitamin E or C (P = 0.03); there was a trend for increasingly higher mean scores with increasing durations of use (P = 0.04). These associations were strongest among women with low dietary intakes of α-tocopherol. Benefits were less consistent for women taking vitamin E alone, with no evidence of higher scores with longer durations of use. Use of specific vitamin C supplements alone had little relation to performance on our cognitive tests. Conclusion: The use of specific vitamin E supplements, but not specific vitamin C supplements, may be related to modest cognitive benefits in older women. [ABSTRACT FROM AUTHOR]

Epigenetic clocks are calculated by combining DNA methylation states across select CpG sites to estimate biologic age, and have been noted as the most successful markers of biologic aging to date. Yet, limited research has considered epigenetic clocks calculated in brain tissue. We used DNA methylation states in dorsolateral prefrontal cortex specimens from 721 older participants of the Religious Orders Study and Rush Memory and Aging Project, to calculate DNA methylation age using four established epigenetic clocks: Hannum, Horvath, PhenoAge, GrimAge, and a new Cortical clock. The four established clocks were trained in blood samples (Hannum, PhenoAge, GrimAge) or using 51 human tissue and cell types (Horvath); the recent Cortical clock is the first trained in postmortem cortical tissue. Participants were recruited beginning in 1994 (Religious Orders Study) and 1997 (Memory and Aging Project), and followed annually with questionnaires and clinical evaluations; brain specimens were obtained for 80–90% of participants. Mean age at death was 88.0 (SD 6.7) years. We used linear regression, logistic regression, and linear mixed models, to examine relations of epigenetic clock ages to neuropathologic and clinical aging phenotypes, controlling for chronologic age, sex, education, and depressive symptomatology. Hannum, Horvath, PhenoAge and Cortical clock ages were related to pathologic diagnosis of Alzheimer's disease (AD), as well as to Aβ load (a hallmark pathology of Alzheimer's disease). However, associations were substantially stronger for the Cortical than other clocks; for example, each standard deviation (SD) increase in Hannum, Horvath, and PhenoAge clock age was related to approximately 30% greater likelihood of pathologic AD (all p < 0.05), while each SD increase in Cortical age was related to 90% greater likelihood of pathologic AD (odds ratio = 1.91, 95% confidence interval 1.38, 2.62). Moreover, Cortical age was significantly related to other AD pathology (eg, mean tau tangle density, p = 0.003), and to odds of neocortical Lewy body pathology (for each SD increase in Cortical age, odds ratio = 2.00, 95% confidence 1.27, 3.17), although no clocks were related to cerebrovascular neuropathology. Cortical age was the only epigenetic clock significantly associated with the clinical phenotypes examined, from dementia to cognitive decline (5 specific cognitive systems, and a global cognitive measure averaging 17 tasks) to Parkinsonian signs. Overall, our findings provide evidence of the critical necessity for bespoke clocks of brain aging for advancing research to understand, and eventually prevent, neurodegenerative diseases of aging. • We calculated five epigenetic clocks in 721 postmortem cortical specimens • Epigenetic clocks trained in blood samples did not predict most neurologic phenotypes • One epigenetic clock, trained in cortex, identified neurodegenerative phenotypes • Findings provide convincing evidence for clocks developed in tissues of interest [ABSTRACT FROM AUTHOR]

An introduction to articles published in this issue is presented including an article on premenopausal women, another on mortality data from a prospective study and an article on studies of estrogen replacement therapy (ERT) that reported data on both cardiovascular disease and cancer.

OBJECTIVE: Individuals with type 2 diabetes have high risk of late-life cognitive impairment, yet little is known about strategies to modify risk. Targeting insulin resistance and vascular complications—both associated with cognitive decline—may be a productive approach. We investigated whether dietary fat, which modulates glucose and lipid metabolism, might influence cognitive decline in older adults with diabetes. RESEARCH DESIGN AND METHODS: Beginning in 1995–1999, we evaluated cognitive function in 1,486 Nurses' Health Study participants, aged ≥70 years, with type 2 diabetes; second evaluations were conducted 2 years later. Dietary fat intake was assessed regularly beginning in 1980; we considered average intake from 1980 (at midlife) through initial cognitive interview and also after diabetes diagnosis. We used multivariate-adjusted linear regression models to obtain mean differences in cognitive decline across tertiles of fat intake. RESULTS: Higher intakes of saturated and trans fat since midlife, and lower polyunsaturated to saturated fat ratio, were each highly associated with worse cognitive decline in these women. On a global score averaging all six cognitive tests, mean decline among women in the highest trans fat tertile was 0.15 standard units worse than that among women in the lowest tertile (95% CI −0.24 to −0.06, P = 0.002); this mean difference was comparable with the difference we find in women 7 years apart in age. Results were similar when we analyzed diet after diabetes diagnosis. CONCLUSIONS: These findings suggest that lower intakes of saturated and trans fat and higher intake of polyunsaturated fat relative to saturated fat may reduce cognitive decline in individuals with type 2 diabetes., Statistics

Background: Recent data indicate that chronic low-level exposure to lead is associated with accelerated declines in cognition in older age, but this has not been examined in women. Objective: We examined biomarkers of lead exposure in relation to performance on a battery of cognitive tests among older women. Methods: Patella and tibia bone lead—measures of cumulative exposure over many years—and blood lead, a measure of recent exposure, were assessed in 587 women 47–74 years of age. We assessed their cognitive function 5 years later using validated telephone interviews. Results: Mean ± SD lead levels in tibia, patella, and blood were 10.5 ± 9.7 μg/g bone, 12.6 ± 11.6 μg/g bone, and 2.9 ± 1.9 μg/dL, respectively, consistent with community-level exposures. In multivariable-adjusted analyses of all cognitive tests combined, levels of all three lead biomarkers were associated with worse cognitive performance. The association between bone lead and letter fluency score differed dramatically from the other bone lead-cognitive score associations, and exclusion of this particular score from the combined analyses strengthened the associations between bone lead and cognitive performance. Results were statistically significant only for tibia lead: one SD increase in tibia lead corresponded to a 0.051-unit lower standardized summary cognitive score (95% confidence interval: −0.099 to −0.003; p = 0.04), similar to the difference in cognitive scores we observed between women who were 3 years apart in age. Conclusions: These findings suggest that cumulative exposure to lead, even at low levels experienced in community settings, may have adverse consequences for women’s cognition in older age.

Background & Aims Studies have reported associations between proton pump inhibitor (PPI) use and dementia. However, data are lacking on long-term PPI use and cognitive function. We therefore examined associations between PPI use and performance in tests of cognitive function. Because of shared clinical indications, we examined associations for H2 receptor antagonists (H2RAs) as a secondary aim. Methods We used prospectively collected data on medication use and other potential risk factors from 13,864 participants in the Nurses’ Health Study II who had completed a self-administered computerized neuropsychological test battery. Multivariable linear regression models were used to examine associations between medication use and composite scores of psychomotor speed and attention, learning and working memory, and overall cognition. Results We observed a modest association between duration of PPI use and scores for psychomotor speed and attention (mean score difference for PPI use of 9−14 years vs never users, −0.06; 95% confidence interval, −0.11 to 0.00; P trend = .03). After controlling for H2RA use, the magnitude of this score difference was attenuated. Among individuals who did not use PPIs regularly, duration of H2RA use was associated with poorer cognitive scores, with the strongest association apparent for learning and working memory (mean score difference for H2RA users of 9−14 years vs never users, −0.20; 95% confidence interval, −0.32 to −0.08; P trend < .001). Conclusions In an analysis of data from the Nurses’ Health Study II, we did not observe a convincing association between PPI use and cognitive function. Our data do not support the suggestion that PPI use increases dementia risk. Because our primary hypothesis related to PPI use, our findings for H2RAs should be interpreted with caution. [ABSTRACT FROM AUTHOR]