Association of enlarged perivascular spaces (ePVS) and MRI markers of small vessel disease (SVD) and neurodegeneration in the Florida Vascular Imaging Phenotypes (FL‐VIP) Study of AD Risk

Abstract

AbstractBackgroundPVS are fluid filled compartments surrounding small intracerebral vessels. They are conduits for fluid transport, exchange, and waste clearance. ePVS are observed in AD, but their relation to SVD markers and neurodegeneration is unknown. We tested whether ePVS are correlated with markers of SVD but not cortical atrophy.MethodWe analyzed subjects’ brains from the FL‐VIP (comprised of all 1Florida ADRC participants with high quality 3T MRI). ePVS were defined as parenchymal hypo/hyperintensities of <3 mm seen on a single axial T1,T2, or FLAIR section through the basal ganglia (BG) and centrum semiovale (CSO). ePVS were graded as 0 (none), 1 (<10), 2 (11‐20), 3 (21‐40), and 4 (>40). The side with highest ePVS count was graded. BGBG and CSO scores were summed to yield a 0‐8 ePVS total. Generalized linear models were used to estimate ePVS score associations with White‐Matter Hyperintensity Volume (WMHV), silent brain infarcts (SBIs), cerebral microbleeds (CMBs), and mean total cortical thickness. We adjusted for demographics, vascular risk factors and comorbidities, and ApoE4 status.ResultOf 228 non‐demented participants (mean age 72±8 years; 61% women, 60% Hispanic, mean education 15±4 years, 33% ApoE4 carriers), 59% were hypertensive, 21% diabetic, 66% hypercholesteremic, and 30% obese. Mean VASCom score was 2.3±1.6. 73% of subjects had a total ePVS score >1. Scores ranged from 0‐7 total (mean 2.5±1.4), 0‐4 for BG (mean 1.3±0.7) and CSO (1.2 ±0.9). In unadjusted analyses, total ePVS correlated with WMHV (r=0.46, p<0001), SBI (r=0.17, p=0.009), and CMB (r=0.16, p=0.016). BG ePVS correlated with WMHV, SBI and CMB. CSO ePVS correlated only with WMHV (r=0.32, p=0.002). In multivariable analyses, ePVS correlated with WMHV (β=4.97, p<0.001), SBI (OR=1.36, p=0.027), and CMB (OR=1.43, p=0.019). BG ePVS remained associated with WMHV, SBI and CMB; and CSO ePVS only with WMHV (β=4.70, p=0.039). Total, BG, and CSO ePVS were not associated with cortical thickness.ConclusionBG ePVS are highly related to MRI markers of SVD, but not total cortical thickness, and therefore may be considered hallmark features of small vessel disease. CSO ePVS may not have as a prominent role in SVD.