ABSTRACT NUMBER: ESOC2026A650 LOCATION MATTERS: DIAGNOSTIC RELEVANCE OF WHITE MATTER HYPERINTENSITIES IN 3481 MEMORY CLINIC PATIENTS

Abstract Background and aims White matter hyperintensities (WMHs) are the most common MRI manifestation of small vessel disease and contribute to 50% of dementias. Yet, in the diagnostic evaluation of individual patients it remains challenging to attribute cognitive deficits to WMHs. Here, we quantified the diagnostic relevance of WMHs, by measuring their explained variance in cognitive function, considering, beyond total WMH volume, WMH location in specific tracts and normative WMH values. Methods We used pooled and harmonized individual patient data (n=3,481, 71±9 years, 50% females) from 11 international memory clinic cohorts through the Meta-VCI-Map consortium. Cognitive function was assessed in 4 domains: attention and executive function, information processing speed, verbal memory and language. WMH volumes were measured in 20 white matter tracts and were norm-adjusted for age and sex, using normative values from 14,876 community-dwelling individuals. Explained variance in cognitive function was measured for demographics (age, sex and education), total WMH volume, and tract-specific volumes and norm-adjusted z-scores. Results Beyond demographics, total and tract-specific WMH volumes explained significantly more variance in attention and executive functioning (9% vs. 12% vs. 15%) and verbal memory (7% vs. 10% vs. 13%). In processing speed, tract-specific volumes, but not total volume, explained significantly more variance than demographics (5% vs. 6% vs. 7%). Norm-adjusting tract-specific volumes did not explain additional variance. Conclusions Considering location doubled diagnostic relevance of WMHs, compared to total volume, explaining more variance in attention and executive function, processing speed and verbal memory. This advocates considering WMH location beyond total volume, although the explained variance by WMHs remains modest. Conflict of interest This study is part of the TAP-dementia consortium: Timely, Accurate and Personalised diagnosis of Dementia (www.tap-dementia.nl). TAP-dementia receives funding from ZonMw (#10510032120003). Van der Lelij: nothing to disclose; Biessels: nothing to disclose. Figure 1 - belongs to Background and aims Figure 2 - belongs to Results