Abstract A111: Driving as a Window to Brain Health: White Matter Hyperintensities, Functional Decline, and Hypertension Treatment

Background: Vascular contributions to cognitive impairment and dementia (VCID) are the most common and preventable cause of late-life cognitive decline, often overlapping with Alzheimer’s disease (AD). Cerebral small vessel disease (CSVD), reflected by white matter hyperintensities (WMH), is a key driver of VCID. Yet the impact of WMH on everyday function remains unclear. Driving, a complex task integrating executive, visuospatial, and motor skills, may serve as a sensitive marker of brain health. We related WMH burden to longitudinal real-world driving behavior, and assessed whether blood pressure control and antihypertensive therapy, key CSVD modifiers, affect these associations. Methods: We studied 220 community-dwelling adults ≥65 years without dementia at baseline. Driving metrics were recorded continuously with in-vehicle dataloggers over 14,781 weeks (mean follow-up 5.6 years). WMH burden was quantified globally and regionally using deep learning-based MRI segmentation. Longitudinal associations with driving outcomes were tested using linear mixed-effects models controlling for demographics, socioeconomic status, and vascular risk. Models included blood pressure control, antihypertensive use, and AD biomarkers (amyloid and tau PET). Results: Greater WMH burden was linked to reduced driving frequency, trip diversity, and adaptability at baseline and with faster decline in these outcomes over time (all P