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. 2025 May 14;96(6):515-527.
doi: 10.1136/jnnp-2024-334925.

Modifiable risk factors for stroke, dementia and late-life depression: a systematic review and DALY-weighted risk factors for a composite outcome

Jasper Senff  1   2   3   4   5 , Reinier Willem Pieter Tack  1   2   3   4   5 , Akashleena Mallick  1   2   3   4 , Leidys Gutierrez-Martinez  1   2   3   4 , Jonathan Duskin  1   2   3   4 , Tamara N Kimball  1   2   3   4   6 , Benjamin Y Q Tan  1   2   3   4   7 , Zeina N Chemali  1   2   8 , Amy Newhouse  1   9 , Christina Kourkoulis  1   2   3   4 , Cyprien Rivier  10   11 , Guido J Falcone  10   11 , Kevin N Sheth  10   11 , Ronald M Lazar  12 , Sarah Ibrahim  13   14   15   16   17 , Aleksandra Pikula  14   15   16   17 , Rudolph E Tanzi  1 , Gregory L Fricchione  8 , Hens Bart Brouwers  5 , Gabriel J E Rinkel  5 , Nirupama Yechoor  1   2   3   4 , Jonathan Rosand  1   2   3   4 , Christopher D Anderson  1   2   3   4   6 , Sanjula D Singh  18   2   3   4
Affiliations

Modifiable risk factors for stroke, dementia and late-life depression: a systematic review and DALY-weighted risk factors for a composite outcome

Jasper Senff et al. J Neurol Neurosurg Psychiatry. .

Abstract

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 shared 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 (β)-coefficients were calculated for a composite outcome. The β-coefficients were normalised 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 (normalised β-coefficient highest category: -34), blood pressure (130), body mass index (70), fasting plasma glucose (94), total cholesterol (22), leisure time cognitive activity (-91), depressive symptoms (57), diet (51), hearing loss (60), kidney function (101), pain (42), physical activity (-56), purpose in life (-50), sleep (76), smoking (91), social engagement (53) and stress (55).

Conclusions: 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.

Prospero registration number: CRD42023476939.

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Conflict of interest statement

Competing interests: AP receives support from the Canadian Institute of Health Research and the Jay and Sari Sonshine Chair in Stroke Prevention and Cerebrovascular Brain Health at the UHN/KBI. CDA receives grants or contracts from the National Institues of Health (Institution), the American Heart Association (Institution) and Bayer AG (Institution). CDA has a leadership or fiduciary role in other boards: Editorial Board Neurology (Journal). BYQT receives grants or contracts from National Medical Research Council, Singapore (Institution) and received payment or honoraria for lectures: International Conference Stroke Updates (ICSU) 2024, Korean Stroke Society (Personal). JR receives support for this present manuscript from the National Institue of Health (Institution) and the American Heart Association (Institution). JR receives grants or contracts from One Mind (Institution). JR receives consulting fees from National Football League (Personal) and Eli Lilly (Personal). JR has a leadership or fiduciary role in: Lancet Neurology (Editorial Board), European Stroke Organisation Journal (Editorial Board), Columbia University (Board of Trustees). JD receives grants or contracts from National Institue of Health (Award No. R25 NS065743). KNS receives grants or contracts from National Institutes of Health (Institution), the American Heart Association (Institution) and Hyperfine (Institution). KNS receives consulting fees for Astrocyte (Personal). Bexorg (Personal), BrainQ (Personal), Rhaeos (Personal), and CereVasc (Personal). KNS has patents planned, issued or pending for real time stroke detection. KNS is on a Data Safety Monitoring Board or Advisory Board: DSMB for Zoll, Sense and Philips. KNS has a leadership or fiduciary role in other boards: Editorial board Annals of Neurology. GLF received frants or contracts from the Psychiatric Clinical Research Training Programme NIHM (1T32MH116140-01). GLF received royalties or licences from: Johns Hopkins University, Belvoir Press, University of Chicago Press, American Psychiatric Press and Adya Health IP license fee. GLF receives consulting fees from Being Health/Mindset LLC (Personal). GLF received payment or honoraria from lectures from Harvard CMEs. GLF participates on a Data Safety Monitoring Board or Advisory Board: Promoting Resilience and Mental Health Among Health Professional Workforce Grant; Advisory Board and The Carter Center Mental Health Task Force. GLF has a leadership or fiduciary role in: Rosalynn Carter Institute for Caregiving Board (unpaid). GLF has stock or stock options in Revival Therapeutics. GLF received grants or contracts from American Heart Association (Award No. 817874 and No. 23BFHSCP1178409) and the National Institute of Health (Award No. U01NS106513 and R01NS093870). RML receives support for the present manuscript and receives grants or contract from the McKnight Brain Research Foundation (Institution). LG-M received grants or contracts from American Heart Association (Award No. 93719). AM, AN, CR, HBB, GJER, JS, RET, SI, SDS, RWPT, TNK, ZNC have nothing to disclose.

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