MRI-Visible Perivascular Spaces and Risk of Incident Dementia

Background and objectivesPerivascular spaces (PVS) visible on magnetic resonance imaging (MRI) scans may represent key aspects in the pathophysiology of stroke and dementia, including cerebral small vessel disease and glymphatic dysfunction. This study aimed to determine the association between MRI-visible PVS burden and the risk of incident dementia.MethodsThe study included community-dwelling Framingham Heart Study Original and Offspring cohort participants with available brain MRI-PVS ratings, free of stroke and dementia. Multivariable Cox proportional hazards regression was used to obtain hazard ratios (HR) and 95% confidence intervals (CI) of the association between MRI-visible PVS and incident dementia. PVS were rated using validated methods in the basal ganglia (BG) and centrum semiovale (CSO). The outcomes included all-cause dementia, Alzheimer's dementia (AD), and vascular dementia.Results1449 participants 50 years of age or older (46% male) were included. Over a median follow-up period of 8.3 years, the incidence of all-cause dementia, AD, and vascular dementia was 15.8%, 12.5% and 2.5%, respectively. In models that adjusted for vascular risk factors and cardiovascular disease, the hazard for dementia increased steadily as PVS burden increased, rising two-fold for those with grade II PVS (HR 2.44, 95% CI 1.51 - 3.93) to five-fold in participants with grade IV (HR 5.05, 95% CI 2.75 - 9.26) compared to grade I PVS in CSO. In the BG, hazards increased 1.6-fold (HR 1.62, 95% CI 1.15 - 2.27) for grade II to 2.6-fold (HR 2.67, 95% CI 1.04 - 6.88) for grade IV compared to grade I PVS. The association remained significant for CSO but not for BG, after adjustment for white matter hyperintensity volume, covert infarcts and total brain volume. Similar findings were observed for AD, but vascular dementia, limited by small number of events, was not statistically significant.DiscussionHigher burden of PVS in CSO was associated with increased risk of developing dementia, independent of vascular risk factors, Total brain and white matter hyperintensity volumes and covert infarcts. This finding supports a role for PVS as a subclinical MRI marker to identify individuals in subclinical stages at high risk of developing dementia who may benefit from early intervention