Aron S. Buchman

Total daily physical activity and the risk of AD and cognitive decline in older adults

Objective: Studies examining the link between objective measures of total daily physical activity and incident Alzheimer disease (AD) are lacking. We tested the hypothesis that an objective measure of total daily physical activity predicts incident AD and cognitive decline. Methods: Total daily exercise and nonexercise physical activity was measured continuously for up to 10 days with actigraphy (Actical®; Philips Healthcare, Bend, OR) from 716 older individuals without dementia participating in the Rush Memory and Aging Project, a prospective, observational cohort study. All participants underwent structured annual clinical examination including a battery of 19 cognitive tests. Results: During an average follow-up of about 4 years, 71 subjects developed clinical AD. In a Cox proportional hazards model adjusting for age, sex, and education, total daily physical activity was associated with incident AD (hazard ratio = 0.477; 95% confidence interval 0.273–0.832). The association remained after adjusting for self-report physical, social, and cognitive activities, as well as current level of motor function, depressive symptoms, chronic health conditions, and APOE allele status. In a linear mixed-effect model, the level of total daily physical activity was associated with the rate of global cognitive decline (estimate 0.033, SE 0.012, p = 0.007). Conclusions: A higher level of total daily physical activity is associated with a reduced risk of AD.

Overview and Findings from the Rush Memory and Aging Project

The Memory and Aging Project is a longitudinal, epidemiologic clinical-pathologic cohort study of common chronic conditions of aging with an emphasis on decline in cognitive and motor function and risk of Alzheimers disease (AD). In this manuscript, we first summarize the study design and methods. Then, we present data on: (1) the relation of motor function to cognition, disability, and death; (2) the relation of risk factors to cognitive and motor outcomes, disability and death; (3) the relation of neuropathologic indices to cognitive outcomes; (4) the relation of risk factors to neuropathologic indices; and (5) additional study findings. The findings are discussed and contextualized.

Change in body mass index and risk of incident Alzheimer disease

Objective: To examine the association of change in body mass index (BMI) with risk of Alzheimer disease (AD). Methods: Nine hundred eighteen older Catholic clergy participating in the Religious Orders Study without dementia at baseline were studied. Outcome measures were the clinical diagnosis of AD and change in cognitive function. Results: During a mean follow-up of 5.5 years, 151 persons developed AD. BMI averaged 27.4 at baseline and declined in about half the participants. In a proportional hazards model adjusted for age, sex, and education, each 1-unit less of BMI at baseline was associated with about a 5% increase in the risk of AD (hazard ratio = 0.944; 95% CI = 0.908 to 0.981), and each 1-unit annual decline in BMI (about the 10th percentile) was associated with about a 35% increase in the risk of AD compared with a person experiencing no change in BMI (about the 50th percentile) (hazard ratio = 0.730; 95% CI = 0.625 to 0.852). The results were similar after controlling for chronic diseases and excluding persons who developed AD during the first 4 years of observation. Random effects models showed that the rate of cognitive decline increased by about 8% for each 1-unit less of BMI at baseline and declined an additional 40%/year in persons losing 1 unit of BMI/year compared with those with no change in BMI. Conclusion: Declining body mass index (BMI) is associated with increased risk of incident Alzheimer disease (AD). Loss of BMI may reflect pathologic processes that contribute to the subsequent development of AD.

The Rush Memory and Aging Project: Study Design and Baseline Characteristics of the Study Cohort.

The long-term objective of the Rush Memory and Aging Project is to identify the postmortem indices linking genetic and environmental risk factors to the development of Alzheimer’s disease (AD). The overall study design involves a detailed assessment of risk factors for AD in older persons without known dementia who agree to annual clinical evaluation and organ donation at the time of death. In contrast to other clinical-pathologic studies which are conducted on special populations, the Rush Memory and Aging Project enrolled a cohort with much greater diversity in terms of educational attainment, in addition to gender, race, and ethnicity. From September of 1997 through April of 2005, more than 1,000 older persons without known dementia from more than 30 residential facilities across the Chicago metropolitan area agreed to participate. Their mean age was 81 years, about a third had 12 or fewer years of education, a third were men, and about 10% were members of a racial or ethnic minority group. More than 950 already have completed their baseline clinical evaluation.

Frailty is Associated With Incident Alzheimer’s Disease and Cognitive Decline in the Elderly

Objective: To assess the association between frailty and incident Alzheimer’s disease (AD) and cognitive decline. Frailty is common in older persons and associated with adverse health outcomes. Methods: Study subjects included 823 older persons without dementia who participated in the Rush Memory and Aging Project, a longitudinal study of aging, and underwent annual assessments of frailty, cognition, and diagnostic evaluation for AD. Results: During a 3-year follow-up, 89 of 823 participants developed AD. In a proportional hazards model, both baseline level of frailty and annual rate of change in frailty were associated with an increased risk of incident AD. Each additional one tenth of a unit increase on the frailty scale at baseline was associated with >9% increased risk of AD (hazard ratio: 2.44; 95% confidence interval (CI): 1.49, 3.37); each one tenth of a unit increase in annual rate of change in frailty was associated with a 12% increased risk of AD (hazard ratio: 3.30; 95% CI: 1.52, 7.13). These results were unchanged in analyses controlling for vascular risk factors and vascular diseases. Results were similar with a categorical measure of frailty instead of a continuous measure. Further, linear mixed-effects models showed that the level of and rate of change in frailty were also associated with the rate of cognitive decline. Conclusion: Increasing frailty is associated with incident AD and the rate of cognitive decline in older persons. These findings suggest that frailty and AD may share similar etiologies. AD = Alzheimer’s disease; PD = Parkinson’s disease; CI = confidence interval; BMI = body mass index; SD = standard deviation.

Physical frailty is associated with incident mild cognitive impairment in community-based older persons.

OBJECTIVES: To test the hypothesis that physical frailty is associated with risk of mild cognitive impairment (MCI).

Purpose in Life Is Associated With Mortality Among Community-Dwelling Older Persons

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.

Effect of a purpose in life on risk of incident Alzheimer disease and mild cognitive impairment in community-dwelling older persons.

CONTEXT Emerging data suggest that psychological and experiential factors are associated with risk of Alzheimer disease (AD), but the association of purpose in life with incident AD is unknown. OBJECTIVE To test the hypothesis that greater purpose in life is associated with a reduced risk of AD. DESIGN Prospective, longitudinal epidemiologic study of aging. SETTING Senior housing facilities and residences across the greater Chicago metropolitan area. PARTICIPANTS More than 900 community-dwelling older persons without dementia from the Rush Memory and Aging Project. MAIN OUTCOME MEASURES Participants underwent baseline evaluations of purpose in life and up to 7 years of detailed annual follow-up clinical evaluations to document incident AD. In subsequent analyses, we examined the association of purpose in life with the precursor to AD, mild cognitive impairment (MCI), and the rate of change in cognitive function. RESULTS During up to 7 years of follow-up (mean, 4.0 years), 155 of 951 persons (16.3%) developed AD. In a proportional hazards model adjusted for age, sex, and education, greater purpose in life was associated with a substantially reduced risk of AD (hazard ratio, 0.48; 95% confidence interval, 0.33-0.69; P < .001). Thus, a person with a high score on the purpose in life measure (score = 4.2, 90th percentile) was approximately 2.4 times more likely to remain free of AD than was a person with a low score (score = 3.0, 10th percentile). This association did not vary along demographic lines and persisted after the addition of terms for depressive symptoms, neuroticism, social network size, and number of chronic medical conditions. In subsequent models, purpose in life also was associated with a reduced risk of MCI (hazard ratio, 0.71; 95% confidence interval, 0.53-0.95; P = .02) and a slower rate of cognitive decline (mean [SE] global cognition estimate, 0.03 [0.01], P < .01). CONCLUSION Greater purpose in life is associated with a reduced risk of AD and MCI in community-dwelling older persons.

Kidney function is associated with the rate of cognitive decline in the elderly

Objective: We tested the hypothesis that impaired kidney function in the elderly is associated with a more rapid rate of cognitive decline. Methods: Baseline serum was used to calculate estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease formula, for 886 elderly without dementia participating in the Rush Memory and Aging Project, a prospective, observational cohort study. Kidney function was also dichotomized into impairment or no impairment based on eGFR < or ≥60 mL/min/1.73 m2. Structured cognitive testing was performed at baseline and at annual evaluations, using a battery of 19 cognitive tests summarized into global cognition and 5 cognitive domains. Results: In mixed-effects models adjusted for age, sex, and education, a lower eGFR at baseline was associated with a more rapid rate of cognitive decline (estimate 0.0008, SE <0.001, p = 0.017). The increased rate of cognitive decline associated with a 15-mL/min/1.73 m2 lower eGFR at baseline (approximately 1 SD) was similar to the effect of being 3 years older at baseline. Impaired kidney function at baseline was associated with a more rapid rate of cognitive decline (estimate −0.028, SE <0.009, p = 0.003). The increased rate of cognitive decline associated with impaired kidney function at baseline was approximately 75% the effect of ApoE4 allele on the rate of cognitive decline. Baseline kidney function was associated with declines in semantic memory, episodic memory, and working memory but not visuospatial abilities or perceptual speed. Conclusion: Impaired kidney function is associated with a more rapid rate of cognitive decline in old age.

Association of Muscle Strength With the Risk of Alzheimer Disease and the Rate of Cognitive Decline in Community-Dwelling Older Persons

BACKGROUND Loss of muscle strength is common and is associated with various adverse health outcomes in old age, but few studies have examined the association of muscle strength with the risk of Alzheimer disease (AD) or mild cognitive impairment (MCI). OBJECTIVE To test the hypothesis that muscle strength is associated with incident AD and MCI. DESIGN Prospective observational cohort study. SETTING Retirement communities across the Chicago, Illinois, metropolitan area. PARTICIPANTS More than 900 community-based older persons without dementia at the baseline evaluation and in whom strength was measured in 9 muscle groups in arms and legs, and in the axial muscles and summarized into a composite measure of muscle strength. MAIN OUTCOME MEASURES Incident AD and MCI and the rate of change in global cognitive function. RESULTS During a mean follow-up of 3.6 years, 138 persons developed AD. In a proportional hazards model adjusted for age, sex, and education status, each 1-U increase in muscle strength at baseline was associated with about a 43% decrease in the risk of AD (hazard ratio, 0.57; 95% confidence interval, 0.41-0.79). The association of muscle strength with AD persisted after adjustment for several covariates, including body mass index, physical activity, pulmonary function, vascular risk factors, vascular diseases, and apolipoprotein E4 status. In a mixed-effects model adjusted for age, sex, education status, and baseline level of global cognition, increased muscle strength was associated with a slower rate of decline in global cognitive function (P < .001). Muscle strength was associated with a decreased risk of MCI, the precursor to AD (hazard ratio, 0.67; 95% confidence interval, 0.54-0.84). CONCLUSION These findings suggest a link between muscle strength, AD, and cognitive decline in older persons.