Determinants of Perivascular Spaces in the General Population: A Pooled Cohort Analysis of Individual Participant Data
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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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Neurology |
| Vol/bind | 100 |
| Udgave nummer | 2 |
| Sider (fra-til) | E107-E122 |
| ISSN | 0028-3878 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
This study was funded by the Austrian Science Fund (projects 13180, 15158, and 12889) and by the Austrian National Bank Jubileumsfond (projects 3905, 4484, and 7776). The sponsors of this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. This work is supported by Bright Focus foundation, Reference No (A2018165F, A-0002043-00-00) and MOE Tier 1 Grant (A-0006106-00-00). The Rotterdam Study ( epib.nl/research/ergo.htm ) is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. This study was further financially supported by the Netherlands Organization for Scientific Research (NWO) Grants No. 948-00-010 and 918-46-615. None of the funding organizations or sponsors were involved in the design and conduct of this study; collection, management analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. We would also like to thank the participants of the Rotterdam Study. SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (Grants No. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs, and the Social Ministry of the Federal State of Mecklenburg-West Pomerania. The study was additionally supported in part by the National Institutes of Health (NIH) grant numbers 1R01AG080821, P30AG066546 and 1U24AG074855. MRI scans in SHIP and SHIP-Trend have been supported by a joint grant from Siemens Healthineers, Erlangen, Germany, and the Federal State of Mecklenburg-West Pomerania. This study was performed using UKB Application Number 23509, and we thank the participants in the UKB imaging study ( ukbiobank.ac.uk/ ). The processing and analysis were performed on the Rekentijd Nationale Computersystemen NWO Grant (2019.014).
Funding Information:
The article processing charge was funded by the authors.
Funding Information:
This study was funded by the Austrian Science Fund (projects 13180, 15158, and 12889) and by the Austrian National Bank Jubileumsfond (projects 3905, 4484, and 7776). The sponsors of this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. This work is supported by Bright Focus foundation, Reference No (A2018165F, A-0002043-00-00) and MOE Tier 1 Grant (A- 0006106-00-00). The Rotterdam Study (epib.nl/research/ ergo.htm) is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education,Culture, and Science; theMinistry ofHealth, Welfare, and Sports; the European Commission (DGXII); and the Municipality of Rotterdam. This study was further financially supported by the Netherlands Organization for Scientific Research (NWO) Grants No. 948-00-010 and 918-46-615. None of the funding organizations or sponsorswere involved in the design and conduct of this study; collection, management analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. We would also like to thank the participants of the Rotterdam Study. SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (GrantsNo. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs, and the Social Ministry of the Federal State ofMecklenburg-West Pomerania. The study was additionally supported in part by the National Institutes of Health (NIH) grant numbers 1R01AG080821, P30AG066546 and 1U24AG074855. MRI scans in SHIP and SHIP-Trend have been supported by a joint grant from Siemens Healthineers, Erlangen, Germany, and the Federal State of Mecklenburg-West Pomerania. This study was performed using UKB Application Number 23509, and we thank the participants in the UKB imaging study (ukbiobank.ac.uk/). The processing and analysis were performed on the Rekentijd Nationale Computersystemen NWO Grant (2019.014).
Publisher Copyright:
© American Academy of Neurology.
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