Neuropathological burden and the degree of frailty in relation to global cognition and dementia.

OBJECTIVE: To test the hypothesis that degree of frailty and neuropathologic burden independently contribute to global cognition and odds of dementia.

METHODS: This was a secondary analysis of a prospective cohort study of older adults living in Illinois, USA. Participants underwent an annual neuropsychological and clinical evaluation. We included 625 participants (mean age 89.7 ± 6.1 years; 67.5% female) who died and had autopsy. We quantified neuropathology using an index measure of 10 neuropathologic features: β-amyloid deposition, hippocampal sclerosis, Lewy bodies, tangle density, TDP-43, cerebral amyloid angiopathy, arteriolosclerosis, atherosclerosis, gross and chronic cerebral infarcts. Clinical consensus determined dementia status, which we coded as no cognitive impairment, mild cognitive impairment, or dementia. A battery of 19 tests spanning multiple domains quantified global cognition. We operationalized frailty using a 41-item frailty index. We employed regression analyses to model relationships between neuropathology, frailty, and dementia.

RESULTS: Both frailty and a neuropathology index were independently associated with global cognition and dementia status. These results held after controlling for traditional pathologic measures in a sample of participants with Alzheimer's clinical syndrome. Frailty improved the fit of the model for dementia status (χ2 (2) = 72.64; p < 0.0001), and explained an additional 11%-12% of the variance in the outcomes.

CONCLUSION: Dementia is a multiply determined condition, to which both general health, as captured by frailty, and neuropathology significantly contribute. This integrative view of dementia and health has implications for prevention and therapy; specifically, future research should evaluate frailty as a means of dementia risk reduction.