Vascular drivers of cerebrospinal fluid movement and enlarged perivascular spaces
5 affiliations
- 1Vanderbilt Memory and Alzheimer's Center Vanderbilt University School of Medicine Nashville Tennessee USA
- 2Vanderbilt Alzheimer's Disease Research Center Nashville Tennessee USA
- 3Vanderbilt Brain Institute Vanderbilt University Nashville Tennessee USA
- 4Department of Neurology Vanderbilt University Medical Center Nashville Tennessee USA
- 5Department of Medicine Vanderbilt University Medical Center Nashville Tennessee USA
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.
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BibTeX
@article{lefevre2026vascular,
title = {{Vascular drivers of cerebrospinal fluid movement and enlarged perivascular spaces}},
author = {James D. LeFevre and Yukti Vyas and Angela L. Jefferson},
journal = {Alzheimer's \& Dementia},
year = {2026},
month = oct,
doi = {10.1002/alz.71927},
url = {https://doi.org/10.1002/alz.71927},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Vascular drivers of cerebrospinal fluid movement and enlarged perivascular spaces
AU - James D. LeFevre
AU - Yukti Vyas
AU - Angela L. Jefferson
PY - 2026
DA - 2026/10/01
JO - Alzheimer's & Dementia
DO - 10.1002/alz.71927
UR - https://doi.org/10.1002/alz.71927
AB - 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.
SN - 1552-5260
SN - 1552-5279
ER -