White Matter Connectivity and Gray Matter Volume Changes Following Donepezil Treatment in Patients With Mild Cognitive Impairment: A Preliminary Study Using Probabilistic Tractography.

Gwang-Won Kim,Kwangsung Park,Gwang-Woo Jeong,Shin-Eui Park

doi:10.3389/fnagi.2020.604940

Abstract

The donepezil treatment is associated with improved cognitive performance in patients with mild cognitive impairment (MCI), and its clinical effectiveness is well-known. However, the impact of the donepezil treatment on the enhanced white matter connectivity in MCI is still unclear. The purpose of this study was to evaluate the thalamo-cortical white matter (WM) connectivity and cortical thickness and gray matter (GM) volume changes in the cortical regions following donepezil treatment in patients with MCI using probabilistic tractography and voxel-based morphometry. Patients with MCI underwent magnetic resonance examinations before and after 6-month donepezil treatment. Compared with healthy controls, patients with MCI showed decreased WM connectivity of the thalamo-lateral prefrontal cortex, as well as reduced thickness in the medial/lateral orbitofrontal cortices (p < 0.05). The thalamo-lateral temporal cortex connectivity in patients with MCI was negatively correlated with Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) (r = −0.76, p = 0.01). The average score of the Korean version of the mini-mental state examination (K-MMSE) in patients with MCI was improved by 7.9% after 6-months of donepezil treatment. However, the patterns of WM connectivity and brain volume change in untreated and treated patients were not significantly different from each other, resulting from multiple comparison corrections. These findings will be valuable in understanding the neurophysiopathological mechanism on MCI as a prodromal phase of Alzheimer's disease in connection with brain functional connectivity and morphometric change.

Highlights

Alzheimer’s disease (AD) is a chronic brain disorder that is associated with neurodegeneration and the progressive development of dementia (Fumagalli et al, 2006)
We have previously reported on a study that evaluated the thalamo-cortical White matter (WM) connectivity in patients with mild cognitive impairment (MCI) using probabilistic tractography
Based on the findings of previous studies (Marenco et al, 2012; Cho et al, 2016) that used probabilistic tractography, we identified 9 brain regions of interest (ROIs) in all, individual T1 images using the FreeSurfer v6.0 software (MGH, Boston, MA, USA) with Desikan-Killiany cortical parcellation as following: seed region; thalamus, target regions; orbitofrontal cortex (OFC), medial prefrontal cortex (MPFC), lateral prefrontal cortex (LPFC), sensorimotor cortex (SMC), parietal cortex (PC), medial temporal cortex (MTC), lateral temporal cortex (LTC), and occipital cortex (OC) (Figure 1) (Dale et al, 1999; Fischl et al, 2002, 2004)

Summary

Introduction

Alzheimer’s disease (AD) is a chronic brain disorder that is associated with neurodegeneration and the progressive development of dementia (Fumagalli et al, 2006). MCI is a prodromal stage of AD, which is a relatively broad clinical condition that involves a slight memory deficit, and in many cases, the condition may represent a transitional state between normal cognition and AD (Morris, 2005). Among the neuropathological alterations in AD, relevant neuronal loss, and synaptic pathology have been studied to be most strongly related to dementia severity and cognitive deficits (Hoy et al, 2017). White matter (WM) degeneration occurs early in the development of AD and is useful in evaluating pathologic AD progression before AD becomes clinically evident (Caso et al, 2015). Several postmortem studies have reported that the early neuropathology in AD manifests in the medial temporal lobe (Hyman et al, 1984; Krasuski et al, 1998)

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