Characterizing spatiotemporal white matter hyperintensity pathophysiology in vivo to disentangle vascular and neurodegenerative contributions

作者：Olivier Parent, Zaki Alasmar, Sophia Osborne, Aurélie Bussy, Manuela Costantino, Jérémie P. Fouquet, Daniela Quesada, Adeline Bernier, Alfonso Fajardo-Valdez, Alexa Pichet-Binette, Ann McQuarrie, Josefina Maranzano, Gabriel A. Devenyi, Christopher J. Steele, Sylvia Villeneuve, the Alzheimer’s Disease Neuroimaging Initiative (ADNI), Mahsa Dadar, M. Mallar Chakravarty · 发表于：Nature Communications · 年份：2026 · DOI：10.1038/s41467-026-70832-2 · 被引用次数：5 · 研究领域：Dementia and Cognitive Impairment Research、Advanced MRI Techniques and Applications、Advanced Neuroimaging Techniques and Applications

White matter hyperintensities (WMHs) are neuroimaging markers widely interpreted as caused by cerebral small vessel disease, yet emerging evidence suggests that a subset may have a neurodegenerative etiology. Current imaging methods have lacked the specificity to disentangle biological processes underlying WMHs in vivo. Here, we used voxel-level normative modeling and seven microstructural MRI markers with complementary biophysical sensitivities to generate single-subject high-resolution WMH pathophysiology maps in a large cohort (n = 32,526). We calculated data-driven spatial patterns of similar WMHs, revealing distinct periventricular, posterior, and anterior clusters. We identified a reproducible WMH signature linked to dementia and Alzheimer's disease, characterized by a posterior predominance and a pathophysiological pattern indicative of selective fiber degeneration. Posterior WMHs connected cortical regions vulnerable to tau pathology. Our framework helps parsing vascular and neurodegenerative contributions of WMHs in vivo, which could alter the course of treatment strategies and provide nuanced interpretations of research findings.