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Physical frailty in older persons is associated with Alzheimer disease pathology

From Rush Alzheimer's Disease Center (A.S.B., J.A.S., S.L., D.A.B.), Department of Neurological Sciences (A.S.B., J.A.S., S.L., D.A.B.), and Department of Pathology (Neuropathology) (J.A.S.), Rush University Medical Center, Chicago, IL.

Address correspondence and reprint requests to Dr. Aron S. Buchman, Rush Alzheimer's Disease Center, Rush University Medical Center, Armour Academic Facility, Suite 1038, 600 S. Paulina St., Chicago, IL 60612 aron_s_buchman{at}rush.edu.

Objective: We examined the extent to which physical frailty in older persons is associated with common age-related brain pathology, including cerebral infarcts, Lewy body pathology, and Alzheimer disease (AD) pathology.

Methods: We studied brain autopsies from 165 deceased participants from the Rush Memory and Aging Project, a longitudinal clinical–pathologic study of aging. Physical frailty, based on four components, including grip strength, time to walk 8 feet, body composition, and fatigue, was assessed at annual clinical evaluations. Multiple regression analyses were used to examine the relation of postmortem neuropathologic findings to frailty proximate to death, controlling for age, sex, and education.

Results: The mean age at death was 88.1 years (SD = 5.7 years). The level of AD pathology was associated with frailty proximate to death ( = 0.252, SE = 0.077, p = 0.001), accounting for 4% of the variance of physical frailty. Neither cerebral infarcts ( = –0.121, SE = 0.115, p = 0.294) nor Lewy body disease pathology ( = 0.07, SE = 0.156, p = 0.678) was associated with frailty. These associations were unchanged after controlling for the time interval from last clinical evaluation to autopsy. The association of AD pathology with frailty did not differ by the presence of dementia, and this association was unchanged even after considering potential confounders, including physical activity; parkinsonian signs; pulmonary function; or history of chronic diseases, including vascular risk factors, vascular disease burden, falls, joint pain, or use of antipsychotic or antihypertensive medications.

Conclusion: Physical frailty in old age is associated with Alzheimer disease pathology in older persons with and without dementia.

Abbreviations: AD = Alzheimer disease; BMI = body mass index; FEV₁ = forced expiratory volume in 1 second; PEF = peak expiratory flow; VC = vital capacity.

Supported by National Institute on Aging grants R01AG17917 and R01AG24480, the Illinois Department of Public Health, and the Robert C. Borwell Endowment Fund.

Disclosure: The authors report no disclosures.

Received December 3, 2007. Accepted in final form May 5, 2008.