Association between topographic distribution of dilated perivascular spaces and Alzheimer’s disease pathologies measured by 18F‐florbetaben and PI‐2620 PET

Abstract

AbstractBackgroundDilated perivascular spaces (DPVS) has been hypothesized to be implicated in the development and/or progression Alzheimer’s disease (AD). However, evidence of a relationship between its topographic distribution and burden of AD pathologies has not been well‐established. We thus aimed to evaluate whether beta‐amyloid (Aβ) and tau burdens measured in positron emission tomography (PET) are associated with topographic distribution of DPVS.MethodFifty‐one patients with amnestic mild cognitive impairment or mild dementia due to possible AD were recruited. Aβ burden was measured as Centiloid (CL) scale from 18F‐florbetaben PET. Burden of tau on regions comprising Braak stage III‐IV of neurofibrillary pathology (Braak H, et al. 2006) was measured as standardized uptake value ratio (SUVR) from tau tracer PI‐2620 PET. DPVS were assessed in the basal ganglia (BG‐DPVS) and in the subcortical white matter (WM‐DPVS) in T1‐sequences of brain MRI. DPVS severities were rated by an established 4‐point semiquantitative score and were then classified as high degree (score>2) or low degree (score≤2) (Martinez‐Ramirez, et al. 2013). The patients were further categorized into 3 groups including patients with higher, equal, and lower score of BG‐DPVS compared to WM‐DPVS (BG>WM, BG = WM, and BG<WM, respectively) (Thanprasertsuk, et al. 2014). Multivariate analyses controlling for age, sex, and MoCA score were applied to ensure independent relationships of DPVS to Aβ‐CL and tau‐SUVR.ResultPatients with high degree of WM‐DPVS (n = 18), compared to ones with the low degree (n = 33), had higher burdens of both Aβ‐CL (median[IQR], 74.29[55.90‐102.02] versus 35.06[11.34‐57.57], p<0.001) and tau‐SUVR (1.46[1.24‐2.15] versus 1.16[1.07‐1.49], p = 0.001). Based on DPVS category, there were differences in both Aβ‐CL (p = 0.001) and tau‐SUVR (p = 0.009) among the BG>WM (n = 20), BG = WM (n = 13), and BG<WM (n = 18) groups, with apparently high disease‐specific pathologies of AD in the BG<WM group (Aβ‐CL = 74.29[46.60‐105.20], and tau‐SUVR = 1.50[1.24‐2.14]). There were no differences in Aβ‐CL and tau‐SUVR between patients with low and high degree of BG‐DPVS.ConclusionOur results suggest that WM‐DPVS is associated with the deposition of Aβ and tau in AD patients, while BG‐DPVS appears to have less substantial association.