Cardiovascular disease as a mediator in the relationship between lifestyle risk factors and cognitive outcomes: a...

Dementia is a major global health challenge and lifestyle modification is a key prevention strategy. Cardiovascular disease (CVD) is hypothesized to mediate lifestyle-dementia relationships, but empirical evidence is unclear. Mediation analysis offers insight into causal mechanisms beyond traditional associations. This scoping review synthesizes the limited available studies applying mediation analysis to examine whether CVD mediates associations between lifestyle factors (smoking, alcohol use, diet, physical activity) and cognitive outcomes in adults aged 45 and older. Of 1309 records screened, five studies met the inclusion criteria, reflecting a small, heterogeneous evidence base. Most examined physical activity (n = 4), with two reporting partial mediation by composite CVD risk scores. Evidence for diet (n = 2) and alcohol (n = 1) was inconclusive, and no studies assessed smoking. Overall, evidence for CVD as a mediator remains tentative, sparse, and inconsistent, highlighting major methodological gaps and an urgent need for robust studies to clarify whether cardiovascular health underpins lifestyle-related dementia risk. HIGHLIGHTS: Five studies were identified that used mediation analysis to explore the role of cardiovascular disease in the relationship between lifestyle risk factors and dementia. Cardiovascular disease may partially mediate the impact of physical activity on brain health. Diet and alcohol consumption showed no clear mediation effects by cardiovascular disease on cognition. Longitudinal, well-powered studies with robust mediation frameworks are urgently needed to evaluate vascular pathways and optimize dementia prevention strategies targeting modifiable lifestyle factors.