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 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

Increased Left Ventricular Mass Index Is Associated With Compromised White Matter Microstructure Among Older Adults

“…Left ventricular (LV) hypertrophy (LVH), a pathologic increase in LV mass, is associated with cerebrovascular disease,1 white matter hyperintensities,2 and cognitive decline3 in aging individuals, particularly elders with hypertension 4, 5. Increased LV mass index (LV mass/body surface area) is an imaging marker that precedes LVH6 and reflects subclinical pathologic remodeling of the ventricular wall.…”

“…Given prior research linking overt LVH to cognitive impairment3 and white matter lesions,2 we hypothesized that higher LV mass index would correlate with compromised white matter microstructure on DTI and worse neuropsychological performance (especially memory) 10. Secondarily, we tested whether associations differed by cognitive diagnosis.…”

Apolipoprotein E ε4 and Later-Life Decline in Cognitive Function and Grip Strength

“…The present analysis, therefore, used all four waves of the Canberra Longitudinal Study spanning 12 years, examined a broader range of cognitive measures that were not investigated in that earlier study individually, and adjusted for potential neuropathology over the entire 12-year period. We also investigated grip strength because decreased grip strength has been identified as a strong predictor of cognitive aging (14,15) and is associated with Alzheimer pathology and disease progression (16).…”

Frailty syndrome and all-cause mortality in demented patients: the Italian Longitudinal Study on Aging

“…Furthermore, several studies have reported that physical frailty is associated with low cognitive performance (Gill et al 1996;Strawbridge et al 1998, Avila-Funes et al 2009), incidence of Alzheimer's disease (AD; Buchman et al 2007), and mild cognitive impairment (Boyle et al 2010) and AD pathology in older persons with and without dementia (Buchman et al 2008). At present, there is no population-based study in which frailty syndrome has been investigated as possible determinant of short-and long-term all-cause mortality in demented patients.…”