Evidence map›Paper›PMID 34928427›Full record

ArticleActa neuropathologica2022

Perivascular space dilation is associated with vascular amyloid-β accumulation in the overlying cortex.

Valentina Perosa, Jan Oltmer, Leon P Munting, Whitney M Freeze, Corinne A Auger, Ashley A Scherlek, Andre J van der Kouwe, Juan Eugenio Iglesias, Alessia Atzeni, Brian J Bacskai and 4 more

Open access · greenAbstract read
In one paragraph

Article in Acta neuropathologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 2 pooled it
10.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

97 citing papers in PubMed, 2 syntheses or guidelines pooled it, 152 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. The role of glymphatic dysfunction in cerebral small vessel disease and vascular cognitive impairment, and therapeutic implications.International journal of stroke : official journal of the International Stroke Society · 2026
    Review
  9. Review
  10. White matterAlzheimer's research & therapy · 2026
    Article
  11. Article
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  13. Observational
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
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37 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 4 countries.

Valentina PerosaDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, J. Philip Kistler Stroke Research Center, Cambridge Str. 175, Suite 300, Boston, MA, 02114, USA. VPEROSA@mgh.harvard.edu.ORCID 0000-0002-3551-5237
Jan OltmerDepartment of Radiology, Massachusetts General Hospital and Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA.
Leon P MuntingMassachusetts General Hospital, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA, USA.
Whitney M FreezeDepartment of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
Corinne A AugerMassachusetts General Hospital, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA, USA.
Ashley A ScherlekMassachusetts General Hospital, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA, USA.
Andre J van der KouweDepartment of Radiology, Massachusetts General Hospital and Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA.
Juan Eugenio IglesiasDepartment of Radiology, Massachusetts General Hospital and Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA.
Alessia AtzeniCentre for Medical Image Computing, University College London, London, UK.
Brian J BacskaiMassachusetts General Hospital, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA, USA.
Anand ViswanathanDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, J. Philip Kistler Stroke Research Center, Cambridge Str. 175, Suite 300, Boston, MA, 02114, USA.
Matthew P FroschMassachusetts General Hospital, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA, USA.
Steven M GreenbergDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, J. Philip Kistler Stroke Research Center, Cambridge Str. 175, Suite 300, Boston, MA, 02114, USA.
Susanne J van VeluwDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, J. Philip Kistler Stroke Research Center, Cambridge Str. 175, Suite 300, Boston, MA, 02114, USA.
Harvard University · USLeiden University Medical Center · NLMassachusetts General Hospital · USRush University Medical Center · USUniversity College London · GB

Funding

The Harvard Clinical and Translational Science CenterUL1TR002541 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2018 to 2022
$93.0M
THE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 1985 to 2018
$42.1M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Sudeshna Das · 2019 to 2026
$36.5M
Vascular Pathology in Early and Asymptomatic Cerebral Amyloid AngiopathyR01AG047975 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI VISWANATHAN, ANAND · 2014 to 2025
$7.5M
Validation of Small-Vessel Disease Neuroimaging Biomarkers in Cerebral Amyloid Angiopathy-Related Cognitive DeclineR01NS104130 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI VISWANATHAN, ANAND · 2018 to 2022
$3.4M
Cerebral microvascular lesions and vascular and neuronal networksRF1NS110054 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI BACSKAI, BRIAN J · 2018 to 2020
$2.7M
Diagnosing the undiagnosable: studies of Alzheimer disease mimics and confounders via "neuropathometry" of dissection photos with 3D scanningR01AG070988 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI IGLESIAS GONZALEZ, JUAN EUGENIO · 2021 to 2025
$2.7M
Open-source software for multi-scale mapping of the human brainRF1MH123195 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI FISCHL, BRUCE, IGLESIAS GONZALEZ, JUAN EUGENIO · 2020 to 2020
$2.0M
Unraveling the mechanisms of microhemorrhages in cerebral amyloid angiopathyR00AG059893 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI VAN VELUW, SUSANNE JANNEKE · 2020 to 2022
$745k
Unraveling the mechanisms of microhemorrhages in cerebral amyloid angiopathy; from ex vivo MRI in humans to in vivo optics in miceK99AG059893 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI VAN VELUW, SUSANNE JANNEKE · 2018 to 2019
$273k
NCATS NIH HHS UL1 TR002541NIA NIH HHS K99 AG059893NIA NIH HHS P30 AG062421NIA NIH HHS P50 AG005134NIA NIH HHS R00 AG059893NIA NIH HHS R01 AG047975NIA NIH HHS R01 AG070988NIH HHS AG059893NIMH NIH HHS RF1 MH123195NINDS NIH HHS R01 NS104130NINDS NIH HHS RF1 NS110054
6 · The paper itself

Abstract

Perivascular spaces (PVS) are compartments surrounding cerebral blood vessels that become visible on MRI when enlarged. Enlarged PVS (EPVS) are commonly seen in patients with cerebral small vessel disease (CSVD) and have been suggested to reflect dysfunctional perivascular clearance of soluble waste products from the brain. In this study, we investigated histopathological correlates of EPVS and how they relate to vascular amyloid-β (Aβ) in cerebral amyloid angiopathy (CAA), a form of CSVD that commonly co-exists with Alzheimer's disease (AD) pathology. We used ex vivo MRI, semi-automatic segmentation and validated deep-learning-based models to quantify EPVS and associated histopathological abnormalities. Severity of MRI-visible PVS during life was significantly associated with severity of MRI-visible PVS on ex vivo MRI in formalin fixed intact hemispheres and corresponded with PVS enlargement on histopathology in the same areas. EPVS were located mainly around the white matter portion of perforating cortical arterioles and their burden was associated with CAA severity in the overlying cortex. Furthermore, we observed markedly reduced smooth muscle cells and increased vascular Aβ accumulation, extending into the WM, in individually affected vessels with an EPVS. Overall, these findings are consistent with the notion that EPVS reflect impaired outward flow along arterioles and have implications for our understanding of perivascular clearance mechanisms, which play an important role in the pathophysiology of CAA and AD.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesCerebral Amyloid AngiopathyGlymphatic SystemDilatationHumansMagnetic Resonance ImagingAmyloid beta-PeptidesCerebral amyloid angiopathyCerebral small vessel diseaseClearanceEnlarged perivascular spacesEx vivo MRI

Identifiers

PMID34928427
PMCPMC9047512
OpenAlexW4200513940

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.