International Perivascular Spaces Meta-analysis Collaboration

About the Project

We are investigating the prognostic value of perivascular spaces (PVS) in Alzheimer's disease, vascular, and mixed dementias, and other neurodegenerative diseases. Using diverse and well-characterised cohorts from Europe, Asia Pacific, and North America, we aim to understand how PVS relates to neurodegenerative and small vessel disease pathologies through advanced imaging and fluid markers. 

Our goal is to determine the independent predictive value of PVS and its role in vascular lesion progression, cognitive decline, white matter integrity, and brain fluid drainage.

Aims

Establish the diagnostic and prognostic value of PVS in patient cohorts with​ Alzheimer’s (AD), vascular, mixed dementias, other neurodegenerative diseases, ​using large, geographically diverse, extensively phenotyped prospective cohorts, ​with collaborators from Europe, Asia Pacific countries, North America and beyond​

Evaluate PVS in the context of:​

• neurodegenerative pathologies including imaging (MRI/PET) and fluid (CSF, plasma) markers; including ATN AD classification ​

• SVD pathologies (MRI markers)​

​Determine pathophysiological PVS implications, in particular in relation to:​

• vascular lesion progression and cognitive decline​

• possible impact of PVS on commonly-used white matter structural integrity MRI measures (diffusion-tensor imaging)

• involvement of PVS in brain interstitial fluid and lymphatic drainage.​

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Previous Weston Collaboration: 

In the previous Weston PVS project, we made significant improvements to our computational PVS pipeline and developed a Docker container to enhance reproducibility. Additionally, we implemented a parallel version of the pipeline to efficiently process large datasets. These enhancements have allowed us to apply our method in large-scale studies, processing some 60,340 scans across 13 different datasets—each with varying protocols, scanners, and locations.

Our method measures PVS count, PVS volume, and PVS morphology, which includes individual length, diameter, and volume. PVS volume is normalised with the brain region volume. The results from analysing both individual and combined datasets indicate that a larger PVS volume is associated with poorer cognitive function after adjusting for key covariates in cross-sectional analyses.

Longitudinally, larger normalised PVS volumes tend to predict a higher likelihood of any cognitive impairment. This association mirrors the cross-sectional findings but can be attenuated across a range of studies, possibly due to variations in participant populations, other long-term changes, or differences in follow-up durations. The relationship between PVS morphology and cognition is less clear, which could be attributed to the measurement methods used.

Collaborators

• The University of Edinburgh (UK)
• Alzheimer Center Amsterdam
• The University Medical Center Utrecht
• Otto von Guericke University Magdeburg
• The German Center for Neurodegenerative Diseases DZNE
• Karolinska Institutet
• Shandong University
• The University of Pennsylvania
• Hospital Clinic Barcelona
• Medical Image Analysis Center Basel
• Taipei Medical University
• University Medical Center Hamburg
• Jules Verne University of Picardy
• Washington University School of Medicine in St. Louis
• The University of Cambridge (UK)

University of Edinburgh team

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• Principal Investigator: Professor Joanna Wardlaw
• Image Analysis: Dr Maria Valdés Hernández​ & Dr Roberto Duarte Coello​
• Statistical Analysis: Dr Francesca Chappell​ & Dr John McFadden
• Research Communication and Science Communication: Ms Jean Balchin, Ms Gillian Joyce & Dr Rosalind Brown