title: 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.
  
  
  CONCLUSIONS
  Physical frailty in old age is associated with Alzheimer disease pathology in older persons with and without dementia.
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Armour Academic Facility, Suite 1038, 600 S Paulina St, Chicago, IL 60612, USA. aron_s_buchman@rush.edu
authors.forename: Aron S
authors.initials: AS
authors.lastname: Buchman
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schneider
authors.forename: Sue
authors.initials: S
authors.lastname: Leurgans
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D002544:Cerebral Infarction / Q000150:complications; D005221:Fatigue / Q000150:complications; D005260:Female; D016330:Frail Elderly; D018737:Hand Strength; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology; D008297:Male; D018908:Muscle Weakness / Q000150:complications; D012307:Risk Factors; D016138:Walking