Longitudinal trajectories of basal forebrain volume in normal aging and Alzheimer's disease

Dysfunction of the cholinergic basal forebrain (BF) system and amyloid-beta (A beta) deposition are early pathological features in Alzheimer's disease (AD). However, their association in early AD is not well-established. This study investigated the nature and magnitude of volume loss in the BF, over an extended period, in 516 older adults who completed A beta-PET and serial magnetic resonance imaging scans. Individuals were grouped at baseline according to the presence of cognitive impairment (CU, CI) and A beta status (A beta-, A beta+). Longitudinal volumetric changes in the BF and hippocampus were assessed across groups. The results indicated that high A beta levels correlated with faster volume loss in the BF and hippocampus, and the effect of A beta varied within BF subregions. Compared to CU A beta+ individuals, A beta-related loss among CI A beta+ adults was much greater in the predominantly cholinergic subregion of Ch4p, whereas no difference was observed for the Ch1/Ch2 region. The findings support early and substantial vulnerability of the BF and further reveal distinctive degeneration of BF subregions during early AD.(c) 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

Automated summary

Dysfunction of the cholinergic basal forebrain system and amyloid-beta deposition are early pathological features in Alzheimer's disease. This study found that Aβ is associated with volume loss in the BF and hippocampus, and the effect varies within BF subregions. The degeneration of BF subregions during early AD also shows distinctive characteristics.