Location patterns of WMH in a multi-cohort study — generalisability and evaluation

Motivation: The location distribution of white matter hyperintensities (WMH) may reflect different pathological processes but consistent characterisation across cohorts is challenging. Goal(s): To develop and validate a framework for identifying WMH distribution patterns across multiple cohorts. Approach: We employed unsupervised clustering to analyse WMH distribution in over 31,000 participants from ADNI3, Insight46, SABRE and UK Biobank, assessed its reproducibility, clinical relevance and predictive potential for progression. Results: Two robust WMH location patterns with distinct clinical profiles were identified. They demonstrated utility in WMH progression prediction. Impact: This framework provides a reproducible solution for identifying WMH patterns in over 31,000 participants across 4 cohorts. By characterising WMH distribution and progression, it informs future research into ageing and neurological disease pathways, and enhances the foundation for personalised care.