18F-AV1451 PET IMAGING IN SUBCORTICAL VASCULAR COGNITIVE IMPAIRMENT

Abstract

Subcortical vascular cognitive impairment (SVCI) is characterized by extensive small vessel disease (SVD) and 30% of these patients have significant amyloid burden. Abnormally hyperphosphorylated tau exist in various types of dementia, yet, the distribution or clinical significance of tau in SVCI patients is not well known. We aimed to evaluate (1) the distribution and spreading pattern of tau in SVCI patients; (2) the effects of amyloid and SVD on tau in SVCI patients; and (3) the effects of tau on cognition. We recruited 61 SVCI, 8 Alzheimer's disease (AD) patients and 20 normal controls (NCs). We calculated SVD score based on the volume of white matter hyperintensities, number of lacunes, and microbleeds. The presence of amyloid-ß was assessed by 18F-florbetaben PET. Paired helical filament tau was measured by 18F-AV1451 PET. We acquired spreading order of tau by sorting the regional frequencies of involvement. Using conditional inference tree method, we classified each patient into in-vivo Braak stages based on mean AV1451 SUVR in the regions of anatomical Braak stages. SVCI patients showed higher AV1451 uptake in the inferior temporal areas compared to NCs, and lower AV1451 uptake in the entire cortical regions except primary sensorimotor and visual cortices compared to AD. Spreading order of tau in SVCI patients showed earlier involvement of entorhinal cortex followed by fusiform gyrus, inferior temporal gyrus, precuneus, and parahippocampal gyrus. In SVCI patients, amyloid positivity was associated with increased AV1451 uptake in the medial-temporal regions, regardless of SVD score. Increased SVD score was associated with increased AV1451 uptake in the inferior temporal regions, regardless of amyloid positivity. AV1451 uptake was associated with poor performance in language, frontal-executive, and general cognitive function.