BACKGROUND: The purpose of this study was to evaluate the cross-sectional and longitudinal association of oral estrogen replacement therapy (ERT) and cognitive function in an older, nondemented sample of women. METHODS: In a prospective cohort of 9651 white women aged 65 years and older enrolled in the Study of Osteoporotic Fractures, a modified Mini-Mental Status Exam (mMMSE), and digit symbol substitution and Trails B tests were administered twice, 4 to 6 years apart. History and current use of oral ERT was documented. Age, educational attainment, and activity limitations were the primary covariates in the analyses; in addition, stroke and depression scores were adjusted in subsets of women with available data. RESULTS: Current and past users of ERT had better initial scores on the mMMSE than did never users, P < .05 and .001, respectively, with better scores for current estrogen hormone users being most apparent among the older and less educated women. The percentages of women scoring 523 of a possible 26 on the mMMSE were 14.3 for current users, 14.5 for past users, and 20.5 for never users, P < .001.However, only past users exhibited smaller declines upon retesting in mMMSE and Trails B performance, P < .05, than did never users. Educational attainment predicted both initial test scores and change scores and was, next to age, the most powerful predictor of cognitive function. CONCLUSIONS: Current oral ERT does not protect against age-related declines in cognitive function in older nondemented women, whereas formal education does protect, even though it had been completed many years earlier. The influence of education in late-life on cognitive function should be tested. J Am Geriatr SOC 47518-523, 1999.mall clinical studies show that estrogen replacement ther- METHODSFrom September 1986 through October 1988, women who were at least 65 years of age were recruited for the SOF in Portland, Oregon, Minneapolis, Minnesota, Baltimore County, Maryland, and the Monongahela Valley near Pittsburgh, Pennsylvania.' Age-eligible women were recruited

Depressive symptoms constitute a risk factor for mortality in frail elderly persons.

Introduction Growing evidence suggests that impairment in rest‐activity rhythms may be a risk factor for cognitive decline and impairment in the aging population. However, previous studies included only a limited set of rest‐activity metrics and produced mixed findings. We studied a comprehensive set of parametric and nonparametric characteristics of rest‐activity rhythms in relation to mild cognitive impairment (MCI) and probable dementia in a cohort of older women. Methods The prospective analysis included 763 women enrolled in two ancillary studies of the Women's Health Initiative (WHI): the WHI Memory Study‐Epidemiology of Cognitive Health Outcomes and Objective Physical Activity and Cardiovascular Health studies. The association between accelerometry‐based rest‐activity parameters and centrally adjudicated MCI and probable dementia were determined using Cox regression models adjusted for sociodemographic characteristics, lifestyle factors, and comorbidities. Results Overall, the results support a prospective association between weakened rest‐activity rhythms (e.g., reduced amplitude and overall rhythmicity) and adverse cognitive outcomes. Specifically, reduced overall rhythmicity (pseudo F statistic), lower amplitude and activity level (amplitude/relative amplitude, mesor, and activity level during active periods of the day [M10]), and later activity timing (acrophase and midpoint of M10) were associated with a higher risk for MCI and probable dementia. Women with lower amplitude and mesor also exhibited faster cognitive decline over follow‐up. Conclusion Weakened rest‐activity rhythms may be predictive markers for cognitive decline, MCI, and dementia among older women.

Altered 24-hour rest-activity rhythms may be associated with cognitive impairment in older adults, but evidence from prospective studies is limited. Non-parametric methods were used to assess actigraphy-based activity patterns in 2,496 older men. Incident cognitive impairment was assessed four times over 12 years using the Modified Mini Mental State Examination (3MS) and Trails B tests, self-reported medication use, and clinical diagnosis. The highest quartile (vs. the lowest) of intradaily variability and the lowest quartiles (vs. the highest) of interdaily stability and relative amplitude were associated with incident cognitive impairment ((Hazard ratio (95% confidence interval): 1.82 (1.31, 2.53)), 1.36 (0.99, 1.86), and 1.85 (1.33, 2.56), respectively). A larger increase in intradaily variability over 7.5 years was associated with a greater subsequent decline in 3MS scores but not in Trails B performance. In conclusion, less stable and more variable rest-activity rhythms may represent early biomarkers of cognitive impairment in older men.