Abstract DP003: Life Stage-Specific Associations Between Vascular Risk Factor Trajectories and Cerebral Small Vessel Disease

Introduction: Cerebral small vessel disease (CSVD) is strongly related to increased risk of stroke and dementia. Long-term exposure to uncontrolled vascular risk factors (VRF), such as systolic and diastolic blood pressure, cigarette smoking, and elevated triglycerides are associated with higher CSVD burden. However, it is unclear whether life stage influences these relationships as the cumulative impact of exposure to VRF may differ depending on the age at which CSVD burden is assessed. Hypothesis: The association between longitudinal VRF trajectories and CSVD burden differs by life stage, with older life stages showing stronger relationships. Methods: Framingham Heart Study participants with six or more repeated VRF measurements during their lifetime and available subsequent brain MRI were included. A multi-marker score quantified CSVD burden by assigning one point to each of the following present MRI markers: cerebral microbleeds, covert infarcts, extensive white matter hyperintensities, cortical superficial siderosis and high burden of perivascular spaces. The score was categorized as 0, 1, 2+ for analysis. Functional principal components analysis was used to summarize VRF trajectories from baseline to MRI assessment. Participants were then grouped by age at MRI (<60, 60–75, >75 years). Within each group, multivariable ordinal logistic regression models were used to assess the association of VRF trajectories and total CSVD score. Results: In 1,614 participants (mean baseline age 33±9 years, 45% male), 134 were younger than 60 years, 840 were between 60-75, and 640 were 75 or older at MRI assessment. After adjusting for age, sex, and cohort, there were no significant associations between VRF trajectories and CSVD score in participants younger than 60. In participants between age 60-75, significant associations were observed with trajectories of systolic and diastolic blood pressure and pulse pressure (p < 0.05), while only trajectories for systolic blood pressure were associated with higher CSVD score in participants older than 75. Conclusions: These findings suggest that the relationship between VRF trajectories and CSVD burden is age-dependent and that the cumulative effects of blood pressure may play a more prominent role in CSVD burden during later life stages. Future research should evaluate whether continuous monitoring of blood pressure and its impact on CSVD burden from mid to late life improves stroke and dementia prevention.