Year: 2026
Type: review
Abstract: Perivascular spaces (PVSs) facilitate cerebrospinal fluid flow and waste clearance, which are critical for maintaining brain homeostasis. Enlarged PVSs (ePVSs) are an emerging marker of cerebral small vessel disease and are implicated in protein accumulation, neurodegeneration, and cognitive decline. While prior reviews have described the anatomy and correlates of ePVSs, the vascular mechanisms that drive perivascular fluid dynamics, and how their dysfunction might lead to ePVSs, have not been reviewed. This review examines how vascular mechanisms drive perivascular fluid dynamics and discusses how their impairment may contribute to ePVS formation and their impact on cognition. We propose an integrated vascular-ePVS hypothesis in which early vascular dysfunction may contribute to impaired waste clearance and ePVS burden, potentially linking early-life vascular health with later proteinopathy and cognitive decline. Elucidating the vascular contributions to ePVSs is imperative to identify therapeutic targets to preserve cognition in Alzheimer's disease and related dementias.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.71927
Institutions: Vanderbilt University, Vanderbilt University Medical Center
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
Awards: High-Performance Computer Cluster for Biomedical Research, White matter and small vessel disease in older adults, G1633318100, Risk factors and prevention targets for abnormal cognitive aging, G173529985, G2477791649, G3109139487, Replacement and Upgrade of a 3T MR Scanner for Research, G4425699080, G5162680913, Left Ventricular Function and Mild Cognitive Impairment, Cardiovascular predictors of cerebrovascular health in older adults, Vanderbilt Alzheimer's Disease Research Center, The Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt Interdisciplinary Training Program in Alzheimer's Disease, Vanderbilt Memory & Aging Project, Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt Alzheimer's Disease Research Center
OpenAlex ID: W7223574576
