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 ϭ 5.7 years). The level of AD pathology was associated with frailty proximate to death ( ϭ 0.252, SE ϭ 0.077, p ϭ 0.001), accounting for 4% of the variance of physical frailty. Neither cerebral infarcts ( ϭ Ϫ0.121, SE ϭ 0.115, p ϭ 0.294) nor Lewy body disease pathology ( ϭ 0.07, SE ϭ 0.156, p ϭ 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. Physical frailty is common in the elderly and associated with adverse health outcomes, but its underlying biology is poorly understood. Although frailty is a heterogeneous syndrome, a number of features, including strength, gait, body composition, and fatigue, are generally accepted as core components of physical frailty.
Conclusion:1,2 Cerebral infarcts and Lewy body disease are known to be associated with impaired physical performance.3,4 Furthermore, recent work by several groups suggests that several core components of frailty, including impaired grip strength, slowed gait, and low body mass index (BMI), predict subsequent development of dementia.5-7 These reports suggest that common brain pathology may contribute to physical frailty in the elderly.We used data from the Rush Memory and Aging Project, 8 a longitudinal epidemiologic clinical-pathologic study of chronic conditions of aging, to examine to what extent common