Abstract
The neuropathological features of Alzheimer's disease (AD) are poorly correlated with the clinical presentation of dementia. However, dementia and frailty are closely linked: both are strongly related to advanced age and vulnerability to adverse health outcomes. It is possible that frailty interacts with neuropathological features of AD to increase vulnerability to cognitive impairment. To examine if frailty is related to AD-related dementia, after controlling for neuropathology. This was a cross-sectional analysis of data from the Rush Memory and Aging Project, a clinico-pathological study of older adults living in retirement communities in the USA. Participants were followed with annual clinical and neuropsychological evaluations and at time of death all had an autopsy. AD neuropathology was quantified using established CERAD criteria. Frailty was operationalized using the deficit accumulation approach, with a frailty index constructed from 38 health variables including function, comorbidities, symptoms, and signs. Cognition was operationalized using a clinical cognitive diagnosis of probable or definite AD. Multiple logistic regression was used to test the relationship between frailty and cognition after controlling for age, sex, education, APOE genotype, and neuropathological burden. 412 adults (82.6±5.7 years, 68.2% female) were included in this analysis. At time of death, 11.9% suffered from AD-type dementia, and 68.2% met neuropathological criteria for AD. Participants with dementia were significantly more frail (F=15.08, p<0.001) and were more likely to have high neuropathological burden (F=13.44, p<0.001) than those without dementia. Interestingly, participants with high burden of AD neuropathology were not more frail (F=1.15, p=0.28). Regression analyses demonstrated that frailty was associated with odds of AD-dementia after controlling for relevant risk factors including AD neuropathology. Specifically, for each 0.1 increase in frailty index score, odds of a clinical cognitive diagnosis increased by 15%. Results here suggest that frailty is associated with the clinical presentation of dementia independently from AD neuropathology burden. This needs to be assessed longitudinally to better elucidate this complex relationship.
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