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

• Published in: Neurology Vol. 95; no. 24; p. e3269
• Main Authors: Wallace, Lindsay M K, Theou, Olga, Darvesh, Sultan, Bennett, David A, Buchman, Aron S, Andrew, Melissa K, Kirkland, Susan A, Fisk, John D, Rockwood, Kenneth
• Format: Journal Article
• Language: English
• Published: United States 15.12.2020
• Subjects: Aged; Aged, 80 and over; Cognition Disorders - epidemiology; Cognition Disorders - physiopathology; Comorbidity; Dementia - epidemiology; Dementia - pathology; Dementia - physiopathology; Female; Frailty - epidemiology; Frailty - physiopathology; Humans; Illinois - epidemiology; Male; Prospective Studies; Regression Analysis; Illinois
• ISSN: 1526-632X
• DOI: 10.1212/wnl.0000000000010944

To test the hypothesis that degree of frailty and neuropathologic burden independently contribute to global cognition and odds of dementia. This was a secondary analysis of a prospective cohort study of older adults living in Illinois. 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 underwent 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, and 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. 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 clinical syndrome. Frailty improved the fit of the model for dementia status (χ [2] 72.64; < 0.0001) and explained an additional 11%-12% of the variance in the outcomes. 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.