title: Association of brain pathology with the progression of frailty in older adults.
abstract: OBJECTIVE
  We tested the hypothesis that brain pathology is associated with the rate of progression of physical frailty in older adults.
  
  
  METHODS
  A total of 791 older adults participating in the Religious Orders Study and Memory and Aging Project had annual clinical evaluations from which a previously established composite measure of physical frailty was derived and brain autopsy after death. A uniform neuropathologic examination included the assessment of macroinfarcts, microinfarcts, atherosclerosis, arteriolosclerosis, Alzheimer disease and Lewy body pathology, and nigral neuronal loss.
  
  
  RESULTS
  Mean follow-up before death was 6.4 years and age at death was 88.5 years. More than 95% of cases had evidence of one or more brain pathologies. In a linear mixed-effect model controlling for age, sex, and education, frailty increased at approximately 0.12 unit/year (estimate 0.117, SE 0.035, p < 0.001). The rate of progression of frailty was accelerated with increasing age (estimate 0.002, SE 0.001, p = 0.012). In separate models, the presence of macroinfarcts, Alzheimer disease and Lewy body pathology, and nigral neuronal loss was associated with a more rapid progression of frailty (all p values ≤0.010). When these 4 brain pathologies were considered together in a single model, Alzheimer disease pathology, macroinfarcts, and nigral neuronal loss showed independent associations with the rate of progression of frailty and accounted for more than 8% of the variance unexplained by demographic variables alone.
  
  
  CONCLUSIONS
  The accumulation of common brain pathologies contributes to progressive physical frailty in old age.
authors: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA. Aron_S_Buchman@rush.edu
authors: Aron S
authors: AS
authors: Buchman
authors: Lei
authors: L
authors: Yu
authors: Robert S
authors: RS
authors: Wilson
authors: Julie A
authors: JA
authors: Schneider
authors: David A
authors: DA
authors: Bennett
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology* / Q000502:physiology; D001927:Brain Diseases / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D016330:Frail Elderly; D006306:Health Surveys; D006801:Humans; D008297:Male; D015233:Models, Statistical; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D013997:Time Factors
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