Association of Basal Forebrain Volume with Amyloid, Tau, and Cognition in Alzheimer's Disease

Abstract

Background: Degeneration of cholinergic basal forebrain (BF) neurons characterizes Alzheimer's disease (AD). However, what role the BF plays in the dynamics of AD pathophysiology has not been investigated precisely. Objective: To investigate the baseline and longitudinal roles of BF along with core neuropathologies in AD. Methods: In this retrospective cohort study, we enrolled 113 subjects (38 amyloid [A beta]-negative cognitively unimpaired, 6 A beta-positive cognitively unimpaired, 39 with prodromal AD, and 30 with AD dementia) who performed brain MRI for BF volume and cortical thickness, F-18-florbetaben PET for A beta, F-18-flortaucipir PET for tau, and detailed cognitive testing longitudinally. We investigated the baseline and longitudinal association of BF volume with A beta and tau standardized uptake value ratio and cognition. Results: Cross-sectionally, lower BF volume was not independently associated with higher cortical A beta, but it was associated with tau burden. Tau burden in the orbitofrontal, insular, lateral temporal, inferior temporo-occipital, and anterior cingulate cortices were associated with progressive BF atrophy. Lower BF volume was associated with faster A beta accumulation, mainly in the prefrontal, anterior temporal, cingulate, and medial occipital cortices. BF volume was associated with progressive decline in language and memory functions regardless of baseline A beta and tau burden. Conclusions: Tau deposition affected progressive BF atrophy, which in turn accelerated amyloid deposition, leading to a vicious cycle. Also, lower baseline BF volume independently predicted deterioration in cognitive function.