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 5 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. Conclusion:The accumulation of common brain pathologies contributes to progressive physical frailty in old age. Physical frailty in older adults is common and associated with a wide range of adverse health outcomes including mortality, disability, cognitive decline, mild cognitive impairment, and Alzheimer disease (AD). [1][2][3][4][5] Frailty may occur in up to 50% or more of adults by the age of 85, making it essential to understand its underlying biology. 6,7 We used data from 791 persons participating in 1 of 2 cohort studies of common chronic conditions of aging that include brain donation at death: the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). 8,9 Prior work in one of these cohorts showed that the level of frailty proximate to death was associated with postmortem indices of AD pathology even in individuals without dementia, suggesting that brain pathology may contribute to frailty.10 This study extends our prior work in 3 important ways. First, we increased the sample size to nearly 800 by including more than 300 persons from a second cohort study. Second, we investigated 6 neuropathologies in addition to AD pathology to assess a broad range of common diseases. Third, we linked pathology to progression of physical frailty in up to 14 annual assessments before death rather than relying on cross-sectional findings with frailty proximate to death.METHODS Participants. Participants were from 2 ongoing studies of chronic conditions of aging. Both studies use common antemortem ...

Relationship of regional brain β-amyloid to gait speed

“…38 In the present work, we focused on the specific contribution of amyloid pathology to gait performance, without taking into account other pathways known to also independently contribute to frailty such as macroinfarcts or nigral neuronal loss. 1 This study showed an association between brain Ab amyloid and slow gait speed in a population of elderly participants with high risk for dementia ranging from healthy to MCI. We provide several possible interpretations of this association, including a neural network perspective of how the neurotoxic effects of regional Ab may be involved in the pathogenesis of motor dysfunction.…”

“…Our findings are consistent with previous neuropathologic evidence showing a relationship between postmortem AD pathology and rate of decline in gait speed prior to death. 1 The brain region showing the strongest association (i.e., greatest regression coefficient) with gait speed was the dorsal posterior putamen. This region was also emphasized by the multivariate analysis with all regions of interest included.…”

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Hypoglycemia in Older People - A Less Well Recognized Risk Factor for Frailty

“…This scale can also be used to help formulate a management plan for persons with frailty. The rate of progression of frailty increases with age and is likely due to diminishing physiologic reserve with ageing however the presence of brain pathologies including cerebrovascular, Alzheimer's and Parkinson's diseases accelerates the rate of progression [51]. The biological processes that underlie frailty are still unclear and likely to be complex and multifactorial.…”