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January 18, 2022; 98 (3) Reviews

Physiology and Clinical Relevance of Enlarged Perivascular Spaces in the Aging Brain

Corey W. Bown, View ORCID ProfileRoxana O. Carare, View ORCID ProfileMatthew S. Schrag, View ORCID ProfileAngela L. Jefferson
First published November 22, 2021, DOI: https://doi.org/10.1212/WNL.0000000000013077
Corey W. Bown
From Vanderbilt Memory and Alzheimer's Center (C.W.B., M.S.S., A.L.J.) and Department of Neurology (C.W.B., M.S.S., A.L.J.), Vanderbilt University Medical Center; Vanderbilt Brain Institute (C.W.B., M.S.S., A.L.J.), Vanderbilt University, Nashville, TN; and Department of Medicine (R.O.C.), University of Southampton, Hampshire, UK
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Roxana O. Carare
From Vanderbilt Memory and Alzheimer's Center (C.W.B., M.S.S., A.L.J.) and Department of Neurology (C.W.B., M.S.S., A.L.J.), Vanderbilt University Medical Center; Vanderbilt Brain Institute (C.W.B., M.S.S., A.L.J.), Vanderbilt University, Nashville, TN; and Department of Medicine (R.O.C.), University of Southampton, Hampshire, UK
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  • ORCID record for Roxana O. Carare
Matthew S. Schrag
From Vanderbilt Memory and Alzheimer's Center (C.W.B., M.S.S., A.L.J.) and Department of Neurology (C.W.B., M.S.S., A.L.J.), Vanderbilt University Medical Center; Vanderbilt Brain Institute (C.W.B., M.S.S., A.L.J.), Vanderbilt University, Nashville, TN; and Department of Medicine (R.O.C.), University of Southampton, Hampshire, UK
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Angela L. Jefferson
From Vanderbilt Memory and Alzheimer's Center (C.W.B., M.S.S., A.L.J.) and Department of Neurology (C.W.B., M.S.S., A.L.J.), Vanderbilt University Medical Center; Vanderbilt Brain Institute (C.W.B., M.S.S., A.L.J.), Vanderbilt University, Nashville, TN; and Department of Medicine (R.O.C.), University of Southampton, Hampshire, UK
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Citation
Physiology and Clinical Relevance of Enlarged Perivascular Spaces in the Aging Brain
Corey W. Bown, Roxana O. Carare, Matthew S. Schrag, Angela L. Jefferson
Neurology Jan 2022, 98 (3) 107-117; DOI: 10.1212/WNL.0000000000013077

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Abstract

Perivascular spaces (PVS) are fluid-filled compartments that are part of the cerebral blood vessel wall and represent the conduit for fluid transport in and out of the brain. PVS are considered pathologic when sufficiently enlarged to be visible on MRI. Recent studies have demonstrated that enlarged PVS (ePVS) may have clinical consequences related to cognition. Emerging literature points to arterial stiffening and abnormal protein aggregation in vessel walls as 2 possible mechanisms that drive ePVS formation. We describe the clinical consequences, anatomy, fluid dynamics, physiology, risk factors, and in vivo quantification methods of ePVS. Given competing views of PVS physiology, we detail the 2 most prominent theoretical views and review ePVS associations with other common small vessel disease markers. Because ePVS are a marker of small vessel disease and ePVS burden is higher in Alzheimer disease, a comprehensive understanding about ePVS is essential in developing prevention and treatment strategies.

Glossary

AD=
Alzheimer disease;
CAA=
cerebral amyloid angiopathy;
ePVS=
enlarged perivascular spaces;
IPAD=
intramural periarterial drainage;
ISF=
interstitial fluid;
PVS=
perivascular spaces;
SMC=
smooth muscle cell;
STRIVE=
Standards for Reporting Vascular Changes on Neuroimaging;
WMH=
white matter hyperintensity

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 95

  • Received April 20, 2021.
  • Accepted in final form October 29, 2021.
  • © 2021 American Academy of Neurology
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