Long-Term Association of Cardiovascular Risk Burden With Dementia Risk: The Role of Life-Course Confounders in an Analysis of Cumulative and Specific Factors

Abstract

Background Preventing dementia through risk factor modification is a global health priority. Although individual cardiovascular risk factors (CVRFs) have been linked to dementia, the cumulative burden of CVRFs, their changes over time, and the role of life-course confounders, especially early-life and psychological factors, remain poorly understood. This study aimed to estimate the longitudinal association between changes in CVRF burden and dementia risk under different hypothetical scenarios.Methods We analyzed 6051 participants from the ARIC (Atherosclerosis Risk in Communities) study, with a median follow-up of 21.9 years. We used the doubly robust g-formula method to estimate the 20-year risk difference for dementia under hypothetical strategies that maintain CVRF burden at different levels over time, explicitly accounting for competing mortality and time-varying confounding.Results At baseline, 23.1 had >= 3 CVRFs. During follow-up, 1008 participants (17) developed dementia. Low birth weight, midlife depression, and poor oral health emerged as important confounders. Maintaining a low CVRF burden was associated with a lower estimated risk of dementia compared with the natural course (risk difference, -4.31 95% compatibility interval, -7.75% to -0.80%), whereas maintaining a high CVRF burden was associated with a higher estimated risk (risk difference, 10.5% 95% compatibility interval, 5.8%-15.7%). Under model assumptions, 41.3% of dementia cases were estimated to be associated with the presence of CVRFs.Conclusions Higher CVRF burden over time was associated with greater dementia risk. Findings suggest that early and sustained management of CVRFs, along with consideration of early-life and psychological factors, may play an important role in dementia prevention strategies.