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Cognitive neurology
Original research
Frailty, lifestyle, genetics and dementia risk
  1. David D Ward1,2,
  2. Janice M Ranson3,
  3. Lindsay M K Wallace1,4,
  4. David J Llewellyn3,5,
  5. Kenneth Rockwood1,6,7,8
  1. 1 Geriatric Medicine Research, Centre for Health Care of the Eldery, Nova Scotia Health Authority, Halifax, Nova Scotia, Canada
  2. 2 Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
  3. 3 College of Medicine and Health, University of Exeter, Exeter, UK
  4. 4 Department of Public Health and Primary Care, Cambridge Institute of Public Health, University of Cambridge, Cambridge, UK
  5. 5 The Alan Turing Institute, London, UK
  6. 6 Division of Geriatric Medicine, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
  7. 7 Division of Neurology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
  8. 8 Institute of Cardiovascular Science, UCL, London, UK
  1. Correspondence to Professor Kenneth Rockwood, Geriatric Medicine Research, Nova Scotia Health Authority, Halifax, Canada; kenneth.rockwood{at}dal.ca

Abstract

Objective To optimise dementia prevention strategies, we must understand the complex relationships between lifestyle behaviours, frailty and genetics.

Methods We explored relationships between frailty index, healthy lifestyle and polygenic risk scores (all assessed at study entry) and incident all-cause dementia as recorded on hospital admission records and death register data.

Results The analytical sample had a mean age of 64.1 years at baseline (SD=2.9) and 53% were women. Incident dementia was detected in 1762 participants (median follow-up time=8.0 years). High frailty was associated with increased dementia risk independently of genetic risk (HR 3.68, 95% CI 3.11 to 4.35). Frailty mediated 44% of the relationship between healthy lifestyle behaviours and dementia risk (indirect effect HR 0.95, 95% CI 0.95 to 0.96). Participants at high genetic risk and with high frailty had 5.8 times greater risk of incident dementia compared with those at low genetic risk and with low frailty (HR 5.81, 95% CI 4.01 to 8.42). Higher genetic risk was most influential in those with low frailty (HR 1.31, 95% CI 1.22 to 1.40) but not influential in those with high frailty (HR 1.09, 95% CI 0.92 to 1.28).

Conclusion Frailty is strongly associated with dementia risk and affects the risk attributable to genetic factors. Frailty should be considered an important modifiable risk factor for dementia and a target for dementia prevention strategies, even among people at high genetic risk.

  • dementia
  • genetics
  • clinical neurology
  • geriatrics

Data availability statement

Data are available on reasonable request. Data may be obtained from a third party and are not publicly available. These data are available for approved researchers from the UK Biobank (https://www.ukbiobank.ac.uk/).

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/jnnp-2021-327396

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    Data availability statement

    Data are available on reasonable request. Data may be obtained from a third party and are not publicly available. These data are available for approved researchers from the UK Biobank (https://www.ukbiobank.ac.uk/).

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    Footnotes

    • DJL and KR are joint senior authors.

    • Twitter @David_D_Ward, @Janice_Ranson, @WallaceLindsay, @DrDJLlewellyn, @Krockdoc

    • Contributors DDW, JMR, LMKW, DJL and KR designed and conceptualised the study; DDW analysed the data, wrote the first draft, and revised all drafts; DDW, JMR, LMKW, DJL and KR interpreted the data; JMR, LMKW, DJL and KR reviewed all drafts; DJL and KR supervised the project. KR accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.

    • Funding This study was funded by a Canadian Institutes of Health Research (CIHR) grant to Kenneth Rockwood PJT-156114, and Team 14 of the Canadian Consortium on Neurodegeneration in Aging (The Canadian Consortium on Neurodegeneration in Aging is supported by a grant from the Canadian Institutes of Health Research with funding from several partners) CIHR grant: CNA-137794.

    • Competing interests DDW, JMR, LMKW and DJL have nothing to report. KR has asserted copyright of the Clinical Frailty Scale through Dalhousie University’s Industry, Liaison and Innovation Office. Use is free for education, research, and not-for-profit health care. Users agree not to change or commercialise the scale. In addition to academic and hospital appointments, KR is cofounder of DGI Clinical, which in the last five years has contracts with pharma and device manufacturers (Biogen, Shire, Hollister, Novartis, Nutricia, Roche, Takeda) on individualiSed outcome measurement. In 2017, he attended an advisory board meeting with Lundbeck on dementia, and in 2020 chaired a Scientific Workshop & Technical Review Panel on frailty for the Singapore National Research Foundation. Otherwise any personal fees are for invited guest lectures, rounds and academic symposia, received directly from event organiSers, for presentations on frailty. He is Associate Director of the Canadian Consortium on Neurodegeneration in Aging, which is funded by the Canadian Institutes for Health Research, the Alzheimer Society of Canada and several other funding partners.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.