Potentially Modifiable Dementia Risk Factors in Canada: An Analysis of Canadian Longitudinal Study on Aging with a Multi-Country Comparison

INTRODUCTION Previous estimates suggested that 40% of dementia cases worldwide are associated with modifiable risk factors, however, these estimates are not known in Canada. We aimed to estimate the population impact of 12 risk factors in Canada, addressing potential differences by sex and age groups, and to compare with other countries. METHODS Prevalence and Population Attributable Fraction (PAF) of 12 modifiable risk factors were estimated using the Canadian Longitudinal Study on Aging baseline dataset (N=26,777). RESULTS Risk factors with the largest PAF were physical inactivity (11.3%), hearing loss (6.9%), and obesity (6.9%). Combined PAF of all risk factors was 49%, and it increased with age. The prevention potential was greater in men (54.1%) than in women (50.5%). CONCLUSIONS Nearly 50% of dementia cases in Canada could be prevented by modifying 12 risk factors across the lifespan and Canadian risk reduction strategies should prioritize targeting physical inactivity, hearing loss, and obesity. ### Competing Interest Statement Son was awarded Alzheimer Society London and Middlesex Doctoral scholarship, Ontario Scholarship Award, and CCNA Trainee Synapse Challenge Funding. Dr. Montero-Odasso reports grants from the CIHR including the Institute of Aging, the CCNA, and Weston Foundation (Weston Brain Institute). Prof. Kivipelto and Dr. Mangialasche are supported by FORTE grant 2023-01125, and are both part of the WW-FINGERS Network Global Scientific Coordinating Center, which is supported by the Alzheimer Disease Data Initiative. Dr. Feldman reports grant funding from CIHR to the CCNA (CNA-163902) and Annovis (QR Pharma), Vivoryon (Probiodrug), AC Immune, and LuMind; service agreements for consulting activities with LuMind, Genentech (DSMB), Roche/Banner (DMC), Tau Consortium (SAB), Samus Therapeutics, Biosplice Therapeutics, Axon Neurosciences, Novo Nordisk Inc., Janssen Research & Development LLC; and travel funding from World Events Forum (ADDF) with no personal funds received and all payments to UCSD. He also reports a philanthropic donation from the Epstein Family Alzheimer's Disease Collaboration for therapeutic research in Alzheimer's Disease with no personal funds received and all payments to UCSD. Dr. Belleville reports grant funding to CCNA from CIHR and ASC. She also reports consulting fees and participation on an advisory board for Lucilab. Dr. Nygaard reports consulting fees from Hoffman-La Roche and Biogen. AL reports a Centre for Aging Brain Health Innovation Grant (CCNA-1-00295). As Scientific Director of CCNA, Dr. Chertkow reports grants from CIHR, Baycrest Health Sciences Foundation, Women's Brain Health Initiative, Alzheimer Society of Canada, Brain Canada, Saskatchewan Health Research Foundation, Alberta Innovates, and Weston Foundation (Weston Brain Institute). As a site investigator for clinical trials, he also receives support from Roche, Lilly, Anavex, and Alector. Dr. Hachinski reports grant from the Weston Foundation (Weston Brain Institute). ### Funding Statement This study was funded by Gait and Brain Health program via fundings of the Canadian Institute of Health and Research (MOP 211220, PJT 153100). This research was made possible using the data/biospecimens collected by the Canadian Longitudinal Study on Aging (CLSA). Funding for the CLSA is provided by the Government of Canada through the Canadian Institutes of Health Research (CIHR) under grant reference: LSA 94473 and the Canadian Foundation for Innovation as well as the following provinces, Newfoundland, Nova Scotia, Quebec, Ontario, Manitoba, Alberta, and British Columbia. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Research Ethics Board of Western University gave ethical approval for this work under application number 120669. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data are available from the Canadian Longitudinal Study on Aging ([www.clsa-elcv.ca][1]) for researchers who meet the criteria for access to de-identified CLSA data. [1]: http://www.clsa-elcv.ca