Physical frailty in older persons is associated with Alzheimer disease pathology

Abstract

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.

Figure Alzheimer disease pathology and frailty The x-axis shows the summary measure of global Alzheimer disease (AD) pathology (quantified standard units), and the y-axis shows composite physical frailty (z score) proximate to death. The scatterplot shows the individual values for physical frailty and AD pathology for participants with dementia (solid circle) and without dementia (triangle) before death. Superimposed are the regression line and 95% CI showing the estimated physical frailty against global AD pathology, from a linear regression model adjusting for age, sex, education, and AD pathology. This model accounts for approximately 22% of the variation in the physical frailty.