Abstract
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. 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. 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 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.
| Original language | English |
|---|---|
| Pages (from-to) | E3269-E3279 |
| Journal | Neurology |
| Volume | 95 |
| Issue number | 24 |
| DOIs | |
| Publication status | Published - 2020 |
Bibliographical note
Funding Information:L.M.K. Wallace is supported by a Doctoral Research Award from the Canadian Institutes of Health Research (CIHR). O. Theou and S. Darvesh report no disclosures relevant to the manuscript. D. Bennett reports grants from the NIH. A.S. Buchman reports no disclosures relevant to the manuscript. M. Andrew reports grants from GSK, Pfizer, Sanofi, and the Canadian Frailty Network unrelated to the current work. S. Kirkland reports no disclosures relevant to the manuscript. J.D. Fisk receives research grant support from the CIHR, the Multiple Sclerosis Society of Canada, Crohn’s and Colitis Canada, and royalty and distribution fees from MAPI Research Trust. K. Rockwood reports personal fees from Lundbeck for attending an advisory board meeting in 2017. K. Rockwood is President and Chief Science Officer of DGI Clinical, which in the last 5 years has contracts with pharma and device manufacturers (Baxter, Baxalta, Shire, Hollister, Nutricia, Roche, Otsuka) on individualized outcome measurement. Otherwise any personal fees are for invited guest lectures and academic symposia, received directly from event organizers, chiefly for presentations on frailty. He is Associate Director of the Canadian Consortium on Neurodegeneration in Aging, which is funded by the CIHR, and with additional funding from the Alzheimer Society of Canada and several other charities, as well as, in its first phase (2013–2018), from Pfizer Canada and Sanofi Canada. He receives career support from the Dalhousie Medical Research Foundation as the Kathryn Allen Weldon Professor of Alzheimer Research and research support from the CIHR, the Nova Scotia Health Research Foundation, the Capital Health Research Fund, and the Fountain Family Innovation Fund of the Nova Scotia Health Authority Foundation. Go to Neurology.org/N for full disclosures.
Funding Information:
L.M.K. Wallace is supported by a doctoral fellowship from the Canadian Institutes of Health Research (CIHR). M.K. Andrew’s work on frailty and dementia is part of a Canadian Consortium on Neurodegeneration in Aging (CCNA) investigation into how multimorbidity modifies the risk of dementia and the patterns of disease expression (Team 14). The CCNA receives funding from the CIHR (CNA-137794) and partner organizations. Kenneth Rockwood’s work on frailty and cognition is supported by CIHR PJT-156114 and by the Dalhousie Medical Research Foundation Kathryn Allen Wel-don Chair of Alzheimer Disease Research. The Rush Memory and Aging Project is supported by NIH grant R01AG17917.
Publisher Copyright:
© 2020 Lippincott Williams and Wilkins. All rights reserved.
ASJC Scopus Subject Areas
- Clinical Neurology
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't