Increased hippocampal-inferior temporal cortex white matter connectivity following donepezil treatment in patients with mild cognitive impairment: A diffusion tensor probabilistic tractography study

Abstract The incidence of Alzheimer’s disease (AD) has been increasing each year; however, few methods are available to identify the effects of treatment for AD. Defective hippocampus has been associated with mild cognitive impairment (MCI), an early stage of AD. However, the effect of donepezil treatment on hippocampus-related networks is unknown. The purpose of this study was to evaluate the hippocampal white matter (WM) connectivity following donepezil treatment in patients with MCI using probabilistic tractography, and to further determine the WM integrity and changes in brain volume. Magnetic resonance imaging and diffusion tensor imaging (DTI) data of patients with MCI before and after 6-month donepezil treatment were acquired. Volumes and DTI scalars of 11 regions of interest comprising the frontal and temporal cortices and subcortical regions were measured. Seed-based structural connectivity analyses were focused on the hippocampus. Compared with healthy controls, patients with MCI showed significantly decreased hippocampal volume and WM connectivity with the superior frontal gyrus, as well as increased mean diffusivity (MD) and radial diffusivity (RD) in the amygdala ( p < 0.05, Bonferroni-corrected). After six months of donepezil treatment, patients with MCI showed increased hippocampal-inferior temporal gyrus (ITG) WM connectivity ( p < 0.05, Bonferroni-corrected), which was normalized to the healthy control. These findings will be useful in developing theories to describe the etiology of MCI and the therapeutic role of anticholinesterases.