Modifiable Risk Factors for Stroke, Dementia, and Late-Life Depression: A Systematic Review and DALY Weighted Risk Factors for a Composite Outcome

Background: At least 60% of stroke, 40% of dementia, and 35% of late-life depression (LLD) are attributable to modifiable risk factors, with great overlap due to a shared underlying pathophysiology. This study aims to systematically identify overlapping risk factors for these diseases and calculate their relative impact on a composite outcome. Methods: A systematic literature review was performed in Pubmed, Embase, and PsycInfo, between January 2000 and September 2023. We included meta-analyses reporting effect sizes of modifiable risk factors on the incidence of stroke, dementia, and/or LLD. The most relevant meta-analyses were selected, and Disability Adjusted Life Year (DALY) weighted beta-coefficients were calculated for a composite outcome. The beta-coefficients were then normalized to assess relative impact. Results: Our search yielded 182 meta-analyses meeting the inclusion criteria, of which 59 were selected to calculate DALY-weighted risk factors for a composite outcome. Identified risk factors included alcohol use (normalized beta-coefficient highest category: -20), blood pressure (87), BMI (42), fasting plasma glucose (57), total cholesterol (14), leisure time cognitive activity (-54), depressive symptoms (34), diet (27), hearing loss (35), kidney function (60), pain (25), physical activity (-34), purpose in life (-30), sleep (44), smoking (58), social engagement (32), and stress (32). Discussion: This study identified overlapping modifiable risk factors and calculated the relative impact of these factors on the risk of a composite outcome of stroke, dementia, and LLD. These findings could guide preventative strategies and serve as an empirical foundation for future development of tools that can empower people to reduce their risk of these diseases. ### Competing Interest Statement C.D.A. receives sponsored research support from the US National Institutes of Health, the American Heart Association, and Bayer AG, and has consulted for ApoPharma. M.C. is supported by the Wellcome Trust [grant number 205339/Z/16/Z]. JR receives sponsored research support from the US National Institutes of Health and the American Heart Association, receives payments for consulting and expert testimony from the National Football League, consulting for Eli Lilly, and has a leadership or fiduciary role at Columbia University and Lancet Neurology. G.F. receives sponsored research support from the National Institute of Mental Health Clinical Global Mental Health Research T32 Fellowship, receives royalties or licenses from Johns Hopkins University Press, University of Chicago Press, Belvoir Press, and the American Psychiatric Press, is on a Data Safety Monitoring Board or Advisory Board of Healthy Hearts Healthy Minds DSMB, is a Board of Directors member at the Rosalynn Carter Institute, and has stock or stock options from Revival Therapeutics Consultant. ### Clinical Protocols ### Funding Statement Funding: US National Institutes of Health and American Heart Association. ### 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: This manuscript only utilized previously published data. All data employed in this study, including the intermediate calculations, are comprehensively presented in the supplementary tables accompanying this manuscript. 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 This manuscript only utilized previously published data. All data employed in this study, including the intermediate calculations, are comprehensively presented in the supplementary tables accompanying this manuscript. Should there be any inquiries or requests for further clarification regarding the data, please contact the corresponding author.