Topographic reference modelling of white matter hyperintensities across the adult lifespan

Voxelwise topographic reference modelling (vTRM) of 42,469 FLAIR WMH masks across 12 adult cohorts maps age- and sex-linked spatial vulnerability and typicality.

• Why it matters: Total WMH volume can miss location-specific differences that may reflect distinct small-vessel, vascular, and neurodegenerative processes tied to cognitive decline and ADRD.
• What they did: vTRM compares individual WMH masks to age- and sex-stratified frequency maps from cognitively unimpaired individuals, then builds paired percentile charts for lesion burden and spatial typicality.
• The result: A quadrant classification using these percentiles shows graded links to ADRD pathophysiology, neurodegeneration, and cognitive impairment, enabling quantification of deviations from normative ageing patterns and WMH phenotype identification.

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