Robust, fully-automated assessment of cerebral perivascular spaces and white matter lesions: a multicentre MRI longitudinal study of their evolution and association with risk of dementia and accelerated brain atrophyResearch in context

• Published in: EBioMedicine 2025-01, Vol.111, p.105523
• Main Authors: Giuseppe Barisano, Michael Iv, Jeiran Choupan, Melanie Hayden-Gephart, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Enchi Liu, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCarli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, Nigel J. Cairns, Erin Householder, Lisa Taylor Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Faber Kelley, Sungeun Kim, Kwangsik Nho, Zaven Kachaturian, Richard Frank, Peter J. Snyder, Susan Molchan, Jeffrey Kaye, Joseph Quinn, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva Meyer, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, John C. Morris, Maria Carroll, Sue Leon, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, Randall Griffith, David Clark, David Geld-macher, John Brockington
• Format: Article
• Language: English
• Subjects: Alzheimer’s disease; Dementia; Glymphatic system; Perivascular spaces; Small vessel disease; White matter lesions
• ISSN: 2352-3964

Background: Perivascular spaces (PVS) on brain MRI are surrogates for small parenchymal blood vessels and their perivascular compartment, and may relate to brain health. However, it is unknown whether PVS can predict dementia risk and brain atrophy trajectories in participants without dementia, as longitudinal studies on PVS are scarce and current methods for PVS assessment lack robustness and inter-scanner reproducibility. Methods: We developed a robust algorithm to automatically assess PVS count and size on clinical MRI, and investigated 1) their relationship with dementia risk and brain atrophy in participants without dementia, 2) their longitudinal evolution, and 3) their potential use as a screening tool in simulated clinical trials. We analysed 46,478 clinical measurements of cognitive functioning and 20,845 brain MRI scans from 10,004 participants (71.1 ± 9.7 years-old, 56.6% women) from three publicly available observational studies on ageing and dementia (the Alzheimer’s Disease Neuroimaging Initiative, the National Alzheimer’s Coordinating Centre database, and the Open Access Series of Imaging Studies). Clinical and MRI data collected between 2004 and 2022 were analysed with consistent methods, controlling for confounding factors, and combined using mixed-effects models. Findings: Our fully-automated method for PVS assessment showed excellent inter-scanner reproducibility (intraclass correlation coefficients >0.8). Fewer PVS and larger PVS diameter at baseline predicted higher dementia risk and accelerated brain atrophy. Longitudinal trajectories of PVS markers differed significantly in participants without dementia who converted to dementia compared with non-converters. In simulated placebo-controlled trials for treatments targeting cognitive decline, screening out participants at low risk of dementia based on our PVS markers enhanced the power of the trial independently of Alzheimer’s disease biomarkers. Interpretation: These robust cerebrovascular markers predict dementia risk and brain atrophy and may improve risk-stratification of patients, potentially reducing cost and increasing throughput of clinical trials to combat dementia. Funding: US National Institutes of Health.