Brainstem atrophy in the early stage of Alzheimer’s disease: a voxel-based morphometry study

Postmortem studies on patients with Alzheimer’s disease (AD) have confirmed that the dorsal raphe nucleus (DRN) in the brainstem is the first brain structure affected in the earliest stage of AD. The present study examined the brainstem in the early stage of AD using magnetic resonance (MR) imaging. T1-weighted MR images of the brains of 81 subjects were obtained from the publicly available Open Access Series of Imaging Studies (OASIS) database, including 27 normal control (NC) subjects, 27 patients with very mild AD (AD-VM) and 27 patients with mild AD (AD-M). The brainstem was interactively segmented from the MR images using ITK-SNAP. The present voxel-based morphometry (VBM) study was designed to investigate the brainstem differences between the AD-VM/AD-M groups and the NC group. The results showed bilateral loss in the pons and the left part of the midbrain in the AD-M group compared to the NC group. The AD-M group showed greater loss in the left midbrain than the AD-VM group (P_FWEcorrected < 0.05). The results revealed that brainstem atrophy occurs in the early stages of AD (Clinical Dementia Rating = 0.5 and 1.0). Most of these findings were also investigated in a multicenter dataset. This is the first VBM study that provides evidence of brainstem alterations in the early stage of AD.