Aging, prevalence and risk factors of MRI-visible enlarged perivascular spaces

Abstract

Background and purpose: Cerebral small vessel disease (CSVD) increases with age and is associated with stroke and cognitive decline. Enlarged Perivascular Spaces (ePVS) is an emerging marker of CSVD, but its prevalence over the life span remain unclear. We characterized the age and sex-specific prevalence of ePVS and relation to age-specific risk factors, in a large community-based sample. Methods: We included 3,710 Framingham Heart Study participants with available brain MRI (average age 61.4±14.6, 46% men). ePVS burden was rated in the centrum semiovale (CSO) and basal ganglia (BG) regions. Individual vascular risk factors were related to ePVS burden in the CSO, BG, and mixed CSO-BG regions using multivariable adjusted ordinal logistic regression analysis. Results: Severe ePVS prevalence increased with age in men and women, and paralleled increase in vascular risk factors, and prevention treatment use. Older age, hypertension (and resulting higher treatment use), higher systolic and diastolic blood pressure, and smoking were associated with higher burden of ePVS in the CSO, BG and mixed regions. Conclusions: Our observations reinforce the hypothesis that ePVS may be a marker of aging-driven brain vascular pathologies, and its association with vascular risk factors support their role as CSVD imaging biomarker.

Enlarged Perivascular Spaces in Relation to Cumulative Blood Pressure Exposure and Cognitive Impairment

“…Previous research has also found that BP is associated with EPVS. A finding from the Framingham Heart Study 15 suggested that higher SBP and DBP values are associated with the severity of EPVS. Compared with individuals with normal BP, individuals with high SBP and DBP showed a 21% and 13% higher risk of having a CS-EPVS score ≥3 points, respectively, and a 26% and 11% higher risk of having a BG-EPVS score ≥3 points, respectively.…”

“…cBP was calculated at 8 time points (2006, 2008, 2010, 2012, 2014, 2016, 2018, and 2021) in the present study. The cumulative systolic BP (cSBP) was calculated as follows: (1) The average SBP of 2 consecutive follow-ups was calculated and multiplied by the number of years between the 2 follow-ups; (2) The calculation process in step (1) was repeated for 7 pairs of consecutive follow-ups, and the 7 values were summed to obtain the cSBP over 15 ). Cumulative diastolic BP (cDBP) and cumulative pulse pressure (cPP) were calculated using the same method.…”

The etiology and evolution of magnetic resonance imaging-visible perivascular spaces: Systematic review and meta-analysis

“…This vascular maladaptation could stem from continued pulsatile barotrauma of affected blood vessels ( Gutierrez et al, 2015 ). However, the association between hypertension and centrum semiovale MVPVS is ambiguous: whereas some studies suggest an increased MVPVS burden in hypertension ( Hurford et al, 2014 ; Zhang et al, 2016 ; Arba et al, 2018 ; Lara et al, 2022 ), some studies do not confirm such a relation ( Potter et al, 2015b ; Riba-Llena et al, 2016 ) or show a decreased MVPVS burden in hypertension ( Charidimou et al, 2014 ). In fact, accumulating evidence indicates that vascular risk factors such as hypertension are rather associated with basal ganglia MVPVS ( Klarenbeek et al, 2013 ), which was corroborated by a recent meta-analysis ( Francis et al, 2019 ).…”

“…In aging, which has consistently been associated with increased MVPVS burden ( Zong et al, 2020 ; Barisano et al, 2021 ; Kim H. G. et al, 2022 ; Lara et al, 2022 ), ex vacuo brain atrophy ( Wardlaw et al, 2020 ), and vascular tortuosity ( Spangler et al, 1994 ; Brown et al, 2002 ; Thore et al, 2007 ) could be more prominent drivers for MVPVS emergence. In addition, increasing exposure to vascular risk factors could also contribute to enlargement of MVPVS in aging ( Lara et al, 2022 ). Of note, however, in our meta-analysis, there was no significant correlation between MVPVS and brain volumes.…”

Genetic considerations in cerebral small vessel diseases

“…PVS visible on brain MRI are detected in most individuals, thus it is not their presence but the burden of PVS that seems to be clinically relevant. In European descendants the prevalence of moderate and severe PVS in the centrum semiovale was 15 and 3%, respectively, while in the basal ganglia was 9 and 1%, respectively ( 20 ). The overall prevalence of PVS in Asian populations seems higher, reported previously between 17–72% ( 13 , 21 ).…”