Abstract
Objective: To examine the relative contributions of frailty and neuropathology to dementia expression in a population-based cohort study. Design: Cross-sectional analysis of observational data. Setting: Population-representative clinicopathological cohort study. Participants: Adults aged 75+ recruited from general practice registries in Cambridge, UK, in 1985. Measurements: A 39-item frailty index and 15-item neuropathological index were used to operationalize frailty and neuropathology, respectively. Dementia status was ascertained by clinical consensus at time of death. Relationships were evaluated using logistic regression models in participants with autopsy records (n = 183). Model fit was assessed using change in deviance. Population attributable fraction for frailty was evaluated in relation to dementia incidence in a representative sample of the survey participants (n = 542). Results: Participants with autopsy were 92.3 ± 4.6 years at time of death, and mostly women (70%). Average frailty index value at last survey before death was 0.34 ± 0.16. People with dementia (63% of the sample) were frailer, had lower MMSE scores, and a higher burden of neuropathology. Frailty and neuropathological burden were significantly and independently associated with dementia status, without interaction; frailty explained an additional 3% of the variance in the model. Assuming a causal relationship and based on population-attributable fraction analyses, preventing severe frailty (Frailty Index ≥ 0.40) could have avoided 14.2% of dementia cases in this population-based cohort. Conclusions: In the very old, frailty contributes to the risk for dementia beyond its relationship with the burden of traditional dementia neuropathologies. Reducing frailty could have important implications for controlling the burden of dementia. Future research on frailty interventions should include dementia risk as a key outcome, public health interventions and policy decisions should consider frailty as a key risk factor for dementia, and biomedical research should focus on elucidating shared mechanisms of frailty and dementia development.
| Original language | English |
|---|---|
| Pages (from-to) | 1035-1043 |
| Number of pages | 9 |
| Journal | International Psychogeriatrics |
| Volume | 33 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 15 2021 |
Bibliographical note
Funding Information:KR is President and Chief Science Officer of DGI Clinical, which in the last 5 years has contracts with pharma and device manufacturers (Baxter, Baxalta, Biogen, Shire, Hollister, Nutricia, Roche, Otsuka) on individualized outcome measurement. In 2017 he attended an advisory board meeting with Lundbeck. Otherwise any personal fees are for invited guest lectures, rounds and academic symposia, received directly from event organizers, for presentations on frailty. He is Associate Director of the Canadian Consortium on Neurodegeneration in Aging, which is funded by the Canadian Institutes of Health Research (CAN-137,794), with additional funding from the Alzheimer Society of Canada and several other charities, as well as from Pfizer Canada and Sanofi Canada (in Phase 1, 2014-2019). The remaining authors have no conflicts of interest to declare.
Funding Information:
We thank all the past CC75C sponsors for financial support spanning two decades (see http://www.cc75c .group.cam.ac.uk/pages/grant/default.htm for full list of project grants) from the Medical Research Council’s funding the survey in this analysis to most recently the Abbeyfield Research Foundation, British Medical Association Foundation for Medical Research and General Nursing Council Trust. SH is currently supported by an ARUK Network Support Grant. The funders had no role in the study design, analysis or writing this paper.
Funding Information:
The authors wish to thank particularly the study respondents, their families, friends and the staff in many care homes and collaborating general practices without whose help none of this research would be possible. The current research team gratefully acknowledge the contributions of previous investigators, past research team members, Addenbrooke’s Hospital mortuary staff and the helpful comments on earlier drafts of this paper from current collaborators (see full list on CC75C study website: www.cc75c.group.cam.ac.uk/pages/ studypersonnel/default.htm). All neuropathology data was generated by Consultant Neuropathologists at Addenbrooke’s Hospital, Cambridge, UK. All slides were prepared by the Cambridge Brain Bank. The Cambridge Brain Bank is supported by the NIHR Cambridge Biomedical Research Centre. LW was generously supported by a Mitacs Globalink fellowship which facilitated this collaboration. The authors would also like to thank Emily Zhao for her assistance in data preparation and management.
Publisher Copyright:
© 2021 International Psychogeriatric Association.
ASJC Scopus Subject Areas
- Clinical Psychology
- Gerontology
- Geriatrics and Gerontology
- Psychiatry and Mental health
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
