ABSTRACT NUMBER: ESOC2026A1084 STRATEGIC WHITE MATTER HYPERINTENSITY LOCATIONS ASSOCIATED WITH TRAIL-MAKING AND STROOP TEST PERFORMANCE: A LESION-SYMPTOM MAPPING STUDY IN 8 POPULATION-BASED COHORTS COMPRISING 11.200 INDIVIDUALS

Abstract Background and aims Lesion location likely affects the impact of white matter hyperintensities (WMH) on cognition. Yet, for most cognitive tests, strategic WMH locations are largely unknown. We aimed to identify strategic locations for the Stroop and Trail Making tests (TMT) — tests known to be affected by small vessel disease (SVD) — in a large pooled analysis of population-based studies. Methods Individual participant data (n=11.200) from eight population-based cohorts were harmonized. We applied region-of-interest–based multivariable regression models across 20 preselected white matter tracts to assess whether tract-specific WMH volume was independently associated with TMT-A, TMT-B, TMT-difference, and Stroop interference ratio (Stroop-IR) after adjustment for total WMH volume. Tracts showing independent associations were defined as “strategic” for that outcome. Results WMH in 12 of the 20 preselected tracts were strategic for cognitive outcomes. Four tracts were strategic for all TMT scores: bilateral corticospinal tracts and superior longitudinal fasciculi (SLF), with the left SLF also strategic for Stroop-IR scores. All additional tracts strategic to TMT-A (left inferior longitudinal fasciculus (ILF) and left temporal segment of the SLF (SLFt)) or to TMT-difference (left anterior thalamic radiation, left cingulum-cingulate gyrus, and right SLFt) were also strategic to TMT-B. In contrast, TMT-B (forceps minor and the right ILF) and Stroop-IR (the left inferior fronto-occipital fasciculus) exhibited unique strategic tract associations (Figure 1). Conclusions TMT subscores and Stroop-IR scores are linked to both shared and distinct strategic WMH locations, reflecting partly overlapping and unique underlying substrates. These findings may help interpret convergent and divergent cognitive test results in SVD. Conflict of interest Floor de Kort: nothing to disclose. Matthijs Biesbroek: nothing to disclose Figure 1 - belongs to Results