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

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 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. Funding US National Institutes of Health and American Heart Association.