Clinical significance of focal ß-amyloid deposition measured by 18F-flutemetamol PET

Abstract

Background Although amyloid PET of typical Alzheimer's disease (AD) shows diffuse ss-amyloid (Ass) deposition, some patients show focal deposition. The clinical significance of this focal Ass is not well understood. We examined the clinical significance of focal Ass deposition in terms of cognition as well as Ass and tau cerebrospinal fluid (CSF) levels. We further evaluated the order of Ass accumulation by visual assessment. Methods We included 310 subjects (125 cognitively unimpaired, 125 mild cognitive impairment, and 60 AD dementia) from 9 referral centers. All patients underwent neuropsychological tests and F-18-flutemetamol (FMM) PET. Seventy-seven patients underwent CSF analysis. Each FMM scan was visually assessed in 10 regions (frontal, precuneus and posterior cingulate, lateral temporal, parietal, and striatum of each hemisphere) and was classified into three groups: No-FMM, Focal-FMM (FMM uptake in 1-9 regions), and Diffuse-FMM (FMM uptake in all 10 regions). Results 53/310 (17.1%) subjects were classified as Focal-FMM. The cognitive level of the Focal-FMM group was better than that of Diffuse-FMM group and worse than that of No-FMM group. Among the Focal-FMM group, those who had FMM uptake to a larger extent or in the striatum had worse cognitive levels. Compared to the Diffuse-FMM group, the Focal-FMM group had a less AD-like CSF profile (increased Ass42 and decreased t-tau, t-tau/Ass42). Among the Focal-FMM group, Ass deposition was most frequently observed in the frontal (62.3%) and least frequently observed in the striatum (43.4%) and temporal (39.6%) regions. Conclusions We suggest that focal Ass deposition is an intermediate stage between no Ass and diffuse Ass deposition. Furthermore, among patients with focal Ass deposition, those who have Ass to a larger extent and striatal involvement show clinical features close to diffuse Ass deposition. Further longitudinal studies are needed to evaluate the disease progression of patients with focal Ass deposition.