White Matter Hyperintensities in Alzheimer’s disease: Pathophysiology, Biomarkers, and Therapeutic Opportunities

White matter hyperintensities (WMHs) are common MRI markers of brain injury in aging and are frequently observed in Alzheimer’s disease (AD) and related dementias. Their presence and progression are associated with cognitive decline, executive dysfunction, memory impairment, reduced attention, slower processing speed, and diminished functional independence, although WMHs represent a heterogeneous set of pathological processes. Vascular dysfunction, cerebral small-vessel disease, blood–brain barrier disruption, inflammation, impaired proteostasis, demyelination, and neurodegeneration may all contribute to their development. Key gaps remain in understanding how WMHs interact with amyloid and tau pathology, how regional WMH patterns influence neuropsychological outcomes, and whether WMHs independently contribute to AD progression. Advances in MRI, PET, and other biomarker technologies are enabling more precise assessment of WMH burden, distribution, and longitudinal change. However, variation in imaging protocols, quantification methods, neuropsychological measures, and clinical definitions continues to limit comparability and integration into routine AD research and care. Further investigation is needed to establish the biological significance, diagnostic value, cognitive relevance, and therapeutic potential of WMHs.This Research Topic aims to advance understanding of the etiology, regional manifestations, neuropsychological and clinical impact, and treatment potential of WMHs in AD and Alzheimer’s disease-related dementias. It will examine the molecular and cellular pathways through which vascular injury, inflammation, impaired proteostasis, neurodegeneration, and related mechanisms contribute to WMH formation and progression. It will also explore the utility of WMHs as biomarkers for early AD detection, prognosis, disease monitoring, and treatment response. Particular emphasis will be placed on relationships between WMHs, cognitive decline, memory, executive function, attention, processing speed, functional independence, amyloid and tau pathology, and other neurodegenerative conditions. The Research Topic will also consider how neuropsychological profiles and longitudinal cognitive assessments can improve patient stratification, disease monitoring, and clinical management.To gather further insights into the complex interplay between WMHs, cognition, and Alzheimer’s disease-related dementias, this Research Topic will encompass molecular, imaging, biomarker, neuropsychological, clinical, and therapeutic research. We welcome articles addressing, but not limited to, the following themes:• Vascular dysfunction, cerebral small-vessel disease, and WMH severity• Molecular and cellular mechanisms underlying WMHs in AD• Neuroinflammation, impaired proteostasis, demyelination, and neurodegeneration• Advances in MRI methods for WMH quantification, segmentation, and visualization• PET, diffusion imaging, perfusion imaging, and other multimodal approaches• WMHs as biomarkers for early AD detection, prognosis, and disease monitoring• Associations between WMHs and memory, executive function, attention, and processing speed• Neuropsychological profiles, functional independence, and cognitive trajectories associated with WMHs• Regional specificity, spatial distribution, and longitudinal WMH progression• Associations among WMHs, cognitive decline, amyloid, tau, and other neurodegenerative pathologies• Clinical significance of WMHs across AD and related dementias• Development of targeted therapeutic strategies to mitigate WMH-related injury• Standardization of imaging, neuropsychological, and clinical assessment• Clinical translation of WMH assessment for diagnosis, prognosis, and treatment monitoring Topic editors: Yin Allison Liu, Shivangi Jain, Lotfi Hacein-Bey, Felipe Godinez Source: https://www.frontiersin.org/research-topics/85982/white-matter-hyperintensities-in-alzheimers-disease-pathophysiology-biomarkers-and-therapeutic-opportunities