MRI-Visible Perivascular Spaces and Risk of Incident Dementia: The Framingham Heart Study
Jose Rafael Romero1, Adlin Pinheiro2, Hugo J Aparicio2
1From the Department of Neurology (J.R.R., H.J.A.), Boston University School of Medicine, MA; Department of Biostatistics (A.P. S.D.), Boston University School of Public Health, MA; Department of Neurology (C.S.D.), University of California at Davis, CA; The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio, TX; and NHLBI's Framingham Heart Study (J.R.R., A.P., H.J.A., S.D., S.S.), MA. joromero@bu.edu.
Background And Objectives:
Perivascular spaces (PVS) visible on 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.
Methods:
This 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 hazard regression was used to obtain hazard ratios (HRs) and 95% CIs 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 dementia (AD), and vascular dementia (VaD).
Results:
One thousand four hundred forty-nine participants 50 years or older (46% male) were included. Over a median follow-up period of 8.3 years, the incidence of all-cause dementia, AD, and VaD 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 2-fold for those with grade II PVS (HR 2.44, 95% CI 1.51-3.93) to 5-fold in participants with grade IV (HR 5.05, 95% CI 2.75-9.26) compared with 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 with grade I PVS. The association remained significant for CSO but not for BG, after adjustment for white matter hyperintensity volume (WMHV), covert infarcts, and total brain volume. Similar findings were observed for AD, but VaD, limited by a small number of events, was not statistically significant.
Discussion:
Higher burden of PVS in CSO was associated with increased risk of developing dementia, independent of vascular risk factors, total brain volume, WMHVs, 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.
Insights
Increased perivascular spaces (PVS) burden on MRI scans, particularly in the centrum semiovale (CSO), is linked to a higher risk of developing dementia. This finding highlights PVS as a potential early marker for dementia risk.
Area of Science:
- Neuroimaging
- Neurology
- Gerontology
Background:
- Perivascular spaces (PVS) on MRI are implicated in stroke and dementia pathophysiology, including cerebral small vessel disease and glymphatic dysfunction.
- Understanding the association between PVS burden and dementia risk is crucial for early identification and intervention.
Purpose of the Study:
- To determine the association between the burden of MRI-visible perivascular spaces (PVS) and the risk of incident dementia.
- To investigate this association in different brain regions, specifically the basal ganglia (BG) and centrum semiovale (CSO).
Main Methods:
- The study analyzed community-dwelling participants from the Framingham Heart Study cohort with available brain MRI-PVS ratings, excluding those with prior stroke or dementia.
- Multivariable Cox proportional hazard regression was employed to assess the relationship between PVS burden and incident dementia (all-cause, Alzheimer's, and vascular dementia).
- PVS were rated in the BG and CSO, and analyses were adjusted for vascular risk factors, cardiovascular disease, white matter hyperintensity volume (WMHV), covert infarcts, and total brain volume.
Main Results:
- A higher burden of PVS in the centrum semiovale (CSO) was significantly associated with an increased risk of all-cause dementia and Alzheimer's dementia.
- Participants with grade II PVS in CSO had a 2-fold increased hazard (HR 2.44), while those with grade IV had a 5-fold increased hazard (HR 5.05) compared to grade I.
- While PVS in the basal ganglia (BG) showed an association, it was not significant after adjusting for WMHV, covert infarcts, and total brain volume.
Conclusions:
- Increased perivascular space burden in the centrum semiovale is an independent predictor of dementia risk.
- MRI-visible PVS, especially in CSO, may serve as a valuable subclinical marker for identifying individuals at high risk for developing dementia.
- These findings support the potential for early intervention in individuals identified with high PVS burden.
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