Abstract White matter hyperintensities (WMHs) are highly prevalent in Alzheimer's disease (AD) and arise from interacting vascular pathologies (including hypertensive small vessel disease and cerebral amyloid angiopathy) alongside inflammatory and neurodegenerative processes. In the era of anti‐amyloid monoclonal antibodies, this heterogeneity is increasingly relevant for both treatment efficacy and safety. WMHs may signal mixed AD–vascular pathology that dilutes the cognitive benefit of amyloid‐targeting therapies and may also index vulnerability of the neurovascular unit that predisposes to amyloid‐related imaging abnormalities (ARIAs), although direct evidence remains limited. In this perspective, we synthesize current knowledge on the origins of WMHs in AD, review advanced magnetic resonance imaging and biomarker approaches that aim to refine lesion characterization in vivo, and discuss how WMHs should be interpreted in memory clinic practice when considering anti‐amyloid therapies. We conclude with a research roadmap to integrate WMH phenotyping into precision risk–benefit assessment and ARIA prediction .
Garnier‐Crussard et al. (Wed,) studied this question.