Determinants of Perivascular Spaces in the General Population: A Pooled Cohort Analysis of Individual Participant Data

Tavia E. Evans, Maria J. Knol, Petra Schwingenschuh, Katharina Wittfeld, Saima Hilal, M. Arfan Ikram, Florian Dubost, Kimberlin M.H. Van Wijnen, Petra Katschnig, Pinar Yilmaz, Marleen De Bruijne, Mohamad Habes, Christopher Chen, Sönke Langer, Henry Völzke, M. Kamran Ikram, Hans J. Grabe, Reinhold Schmidt, Hieab H.H. Adams, Meike W. Vernooij

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Background and ObjectivesPerivascular spaces (PVS) are emerging markers of cerebral small vessel disease (CSVD), but research on their determinants has been hampered by conflicting results from small single studies using heterogeneous rating methods. In this study, we therefore aimed to identify determinants of PVS burden in a pooled analysis of multiple cohort studies using 1 harmonized PVS rating method.MethodsIndividuals from 10 population-based cohort studies with adult participants from the Uniform Neuro-Imaging of Virchow-Robin Spaces Enlargement consortium and the UK Biobank were included. On MRI scans, we counted PVS in 4 brain regions (mesencephalon, hippocampus, basal ganglia, and centrum semiovale) according to a uniform and validated rating protocol, both manually and automated using a deep learning algorithm. As potential determinants, we considered demographics, cardiovascular risk factors, APOE genotypes, and other imaging markers of CSVD. Negative binomial regression models were used to examine the association between these determinants and PVS counts.ResultsIn total, 39,976 individuals were included (age range 20-96 years). The average count of PVS in the 4 regions increased from the age 20 years (0-1 PVS) to 90 years (2-7 PVS). Men had more mesencephalic PVS (OR [95% CI] = 1.13 [1.08-1.18] compared with women), but less hippocampal PVS (0.82 [0.81-0.83]). Higher blood pressure, particularly diastolic pressure, was associated with more PVS in all regions (ORs between 1.04-1.05). Hippocampal PVS showed higher counts with higher high-density lipoprotein cholesterol levels (1.02 [1.01-1.02]), glucose levels (1.02 [1.01-1.03]), and APOE ϵ4-alleles (1.02 [1.01-1.04]). Furthermore, white matter hyperintensity volume and presence of lacunes were associated with PVS in multiple regions, but most strongly with the basal ganglia (1.13 [1.12-1.14] and 1.10 [1.09-1.12], respectively).DiscussionVarious factors are associated with the burden of PVS, in part regionally specific, which points toward a multifactorial origin beyond what can be expected from PVS-related risk factor profiles. This study highlights the power of collaborative efforts in population neuroimaging research.

Original languageEnglish
Pages (from-to)E107-E122
JournalNeurology
Volume100
Issue number2
DOIs
StatePublished - 10 Jan 2023
Externally publishedYes

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