Abstract
INTRODUCTION: White matter hyperintensities (WMHs) are a biomarker of small vessel cerebrovascular changes that can emerge early in Alzheimer's disease. While global WMHs correlate with cognitive decline, the impact of regional WMHs remains understudied. We examined associations of regional WMH distributions with longitudinal cognition. METHODS: National Alzheimer's Coordinating Center cohort participants (n = 1047; cognitively normal, mild cognitive impairment, dementia) completed neuropsychological and neuroimaging assessments. Hierarchical cluster analysis identified baseline regional WMH patterns, and linear mixed-effects models assessed 2 year change in cognitive domain by cluster. RESULTS: Five WMH clusters emerged. Compared to those with low WMH burden, participants in the mild occipital and high parieto-occipital clusters had faster memory decline; mild fronto-parietal and high parieto-occipital clusters showed faster executive decline; and mild and high fronto-parietal and high parieto-occipital clusters had faster language decline. DISCUSSION: Regional WMH distributions showed distinct trajectories. Posterior WMHs were most associated with memory decline, while even mild WMHs accelerated decline in some domains. HIGHLIGHTS: Hierarchical cluster analysis identified five white matter hyperintensity (WMH) patterns. Posterior WMHs were most related to memory decline. Mild frontal and elevated posterior patterns were associated with executive function decline. Multiple WMH patterns were associated with language decline.