Alzheimer disease (AD) is one of the most dreaded consequences of aging, and the identification of modifiable factors associated with the risk of AD is a top public health priority for the 21st century, particularly given the large and rapidly increasing aging population. Although relatively few such risk factors have been identified, emerging data suggest that a variety of potentially modifiable psychological factors (eg, conscientiousness, extraversion, and neuroticism) and experiential factors (eg, social networks) are associated with risk of AD.^1-4 Purpose in life, the psychological tendency to derive meaning from life's experiences and to possess a sense of intentionality and goal directedness that guides behavior, has long been hypothesized to protect against adverse health outcomes.^5-9 Indeed, purpose in life has been linked to positive outcomes, including better mental health and happiness, and it was recently reported that purpose in life is associated with longevity.^9-14 However, the association of purpose in life with the risk of AD remains unknown.

OBJECTIVES: To test the hypothesis that physical frailty is associated with risk of mild cognitive impairment (MCI). DESIGN: Prospective, observational cohort study. SETTING: Approximately 40 retirement communities across the Chicago metropolitan area. PARTICIPANTS: More than 750 older persons without cognitive impairment at baseline. MEASUREMENTS: Physical frailty, based on four components (grip strength, timed walk, body composition, and fatigue), was assessed at baseline, and cognitive function was assessed annually. Proportional hazards models adjusted for age, sex, and education were used to examine the association between physical frailty and the risk of incident MCI, and mixed effect models were used to examine the association between frailty and the rate of change in cognition. RESULTS: During up to 12 years of annual follow‐up, 305 of 761 (40%) persons developed MCI. In a proportional hazards model adjusted for age, sex, and education, physical frailty was associated with a high risk of incident MCI, such that each one‐unit increase in physical frailty was associated with a 63% increase in the risk of MCI (hazard ratio=1.63; 95% confidence interval=1.27–2.08). This association persisted in analyses that required MCI to persist for at least 1 year and after controlling for depressive symptoms, disability, vascular risk factors, and vascular diseases. Furthermore, a higher level of physical frailty was associated with a faster rate of decline in global cognition and five cognitive systems (episodic memory, semantic memory, working memory, perceptual speed, and visuospatial abilities). CONCLUSION: Physical frailty is associated with risk of MCI and a rapid rate of cognitive decline in aging.

Objective: To assess the association between purpose in life and all-cause mortality in community-dwelling elderly persons. Methods: We used data from 1238 older persons without dementia from two longitudinal cohort studies (Rush Memory and Aging Project and Minority Aging Research Study) with baseline evaluations of purpose in life and up to 5 years of follow-up to test the hypothesis that greater purpose in life is associated with a reduced risk of mortality among community-dwelling older persons. Results: The mean ± standard deviation score on the purpose in life measure at baseline was 3.7 ± 0.5 (range = 2–5), with higher scores indicating greater purpose in life. During the 5-year follow-up (mean = 2.7 years), 151 of 1238 persons (12.2%) died. In a proportional hazards model adjusted for age, sex, education, and race, a higher level of purpose in life was associated with a substantially reduced risk of mortality (hazard ratio = 0.60, 95% Confidence Interval = 0.42, 0.87). Thus, the hazard rate for a person with a high score on the purpose in life measure (score = 4.2, 90th percentile) was about 57% of the hazard rate of a person with a low score (score = 3.1, 10th percentile). The association of purpose in life with mortality did not differ among men and women or whites and blacks. Further, the finding persisted after the addition of terms for several potential confounders, including depressive symptoms, disability, neuroticism, the number of chronic medical conditions, and income. Conclusion: Greater purpose in life is associated with a reduced risk of all-cause mortality among community-dwelling older persons. MAP = Memory and Aging Project; MARS = Minority Aging Research Study; CES-D = Center for Epidemiologic Studies Depression scale.

Objective: We tested the hypothesis that cerebral amyloid angiopathy (CAA) is related to Alzheimer disease (AD) dementia and decline in multiple cognitive systems in old age, independent of AD plaque and tangle pathology and other common age-related neuropathologies. Methods: Participants (n = 1,113) came from 2 longitudinal clinical-pathologic studies of aging, the Rush Memory and Aging Project and the Religious Orders Study. All underwent annual clinical evaluations including detailed cognitive testing for a mean of 7.1 years before death. Clinical diagnoses of AD were established after reviewing all clinical data, blinded to neuropathologic information. Neuropathologic examinations provided measures of CAA, AD pathology, macroscopic infarcts, microinfarcts, and neocortical Lewy bodies. The association of CAA with AD dementia was examined using logistic regression models, and its association with cognitive decline was examined using linear mixed models. Results: CAA was common, present in 78.9% of participants, and moderately related to AD pathology (ρ = 0.401, p < 0.0001). In analyses adjusted for plaques, tangles, and other common age-related neuropathologies, CAA was associated with an increased odds of AD dementia (odds ratio = 1.237, 95% confidence interval 1.082–1.414) and an increased rate of decline in global cognition, perceptual speed, episodic memory, and semantic memory. The associations of CAA with cognitive outcomes were not driven by the presence of capillary involvement. Conclusions: CAA is an important determinant of AD dementia and decline in multiple cognitive systems in old age.

Although Alzheimer disease (AD) is characterized clinically by a progressive deterioration in memory and other cognitive abilities, it is associated with various noncognitive features, including affective manifestations (eg, depressive symptoms) and impaired motor function (eg, gait impairment).^1-5 Recent data suggest that these noncognitive features may be early signs of AD, as they often predict the onset of clinical AD.^6-10 Although grip strength is related to the risk of AD, few studies^11-13 have examined grip strength, and the more general association of muscle strength (measured in multiple body regions) with incident AD remains unknown. Furthermore, body mass index (BMI) and physical activity are related to the risk of AD,^14-17 yet it is unclear whether the association of muscle strength with AD is independent of these important confounding variables.