Patricia A. Boyle

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.

Prediction of functional status from neuropsychological tests in community-dwelling elderly individuals.

Age-related dysfunction of frontal systems can result in deficits in planning, organization, self-control, and awareness of problems, which are likely to affect the ability to care for ones self. The purpose of this study was to determine the relationship between age-related frontal/executive deficits and impairment in instrumental activities of daily living (IADLs) in elderly individuals. Twenty-seven community-dwelling individuals were administered a comprehensive battery of neuropsychological tests and a performance-based evaluation of IADLs. Multiple regression analyses indicated that executive function and depression severity accounted for a significant proportion of variance in IADLs, with executive function making the greatest contribution. Tests measuring other cognitive functions, such as memory, language, and spatial skills, did not contribute significantly to the prediction of functional status. Furthermore, executive measures accounted for more variance than other demographic characteristics such as general health status, age, and educational level. The results of this study indicate that executive dysfunction in normal aging may be the best predictor of functional decline. A better understanding of the mechanisms that underlie IADL skills will ultimately aid in the development of compensatory and intervention strategies designed to delay the onset of assisted living and nursing home placement.

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).

Tests of Executive Function Predict Instrumental Activities of Daily Living in Community-Dwelling Older Individuals

The purpose of this study was to examine the utility of specific tests of executive functioning for predicting instrumental activities of daily living (IADLs) in community-dwelling older individuals (n = 30). In addition to tests of frontal and executive functioning, performance based and caregiver-rated evaluations of IADLs were obtained. Results indicated that different tests of executive functioning were associated with outcomes on performance-based versus caregiver-rated assessments of IADLs. Specifically, the Trail Making Test (Part B) made a significant and unique contribution to the prediction of performance-based IADLs. In contrast, verbal fluency performance and Trail Making Test performance made significant independent contributions to the prediction of IADLs as reported by a caregiver. These findings suggest that different aspects of frontal and executive functions may be related to IADLs, depending on the type of assessment instrument used.

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.

Subcortical infarcts, Alzheimer's disease pathology, and memory function in older persons

Examine the effects of subcortical infarcts with Alzheimers disease (AD) pathology on dementia, episodic memory, and other cognitive abilities in older persons.

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.

The Neuropathology of Older Persons with and Without Dementia from Community versus Clinic Cohorts

Community-based cohorts of older persons may differ neuropathologically from clinic-based cohorts. This study investigated age-related pathologies in persons with and without dementia and included autopsied participants from two community-based cohorts, the Rush Religious Orders Study (n=386) and the Memory and Aging Project (n=195), and one clinic-based cohort, the Clinical Core of the Rush Alzheimers Disease Center (n=392). Final clinical diagnoses included no cognitive impairment (n=202), mild cognitive impairment (MCI) (n=150), probable Alzheimers disease (AD) (n=474), possible AD (n=88), and other dementias (n=59). Postmortem diagnoses included pathologic AD, cerebral infarcts, and Lewy body disease. Community-based persons with clinical AD had less severe AD pathology (p<0.001) and had more cerebral infarcts (p<0.001) compared to clinic-based persons. Additionally, community-based persons with MCI had more infarcts compared to clinic-based persons. Overall, there was a higher proportion of Lewy bodies and atypical pathologies in the clinic-based compared to the community-based cohorts (p<0.001). Community-based persons with probable AD show less severe AD pathology and more often have infarcts and mixed pathologies; those with MCI more often have infarcts and mixed pathologies. Overall, clinic-based persons have more Lewy bodies and atypical pathologies. The spectrum of pathologies underlying cognitive impairment in clinic-based cohorts differs from community-based cohorts.