Long-Term Effect of Acetylcholinesterase Inhibitors on the Dorsal Attention Network of Alzheimer's Disease Patients: A Pilot Study Using Resting-State Functional Magnetic Resonance Imaging

Ken-Ichiro Yamashita; Taira Uehara; Yoshihide Taniwaki; Shozo Tobimatsu; Jun-Ichi Kira

doi:10.3389/fnagi.2022.810206

Long-Term Effect of Acetylcholinesterase Inhibitors on the Dorsal Attention Network of Alzheimer's Disease Patients: A Pilot Study Using Resting-State Functional Magnetic Resonance Imaging

Front Aging Neurosci. 2022 Apr 5:14:810206. doi: 10.3389/fnagi.2022.810206. eCollection 2022.

Authors

Ken-Ichiro Yamashita^{1

2}, Taira Uehara³, Yoshihide Taniwaki⁴, Shozo Tobimatsu⁵, Jun-Ichi Kira^{1

2}

Affiliations

¹ Translational Neuroscience Center, Graduate School of Medicine, International University of Health and Welfare, Otawara, Japan.
² Department of Neurology, Brain and Nerve Center, Fukuoka Central Hospital, Fukuoka, Japan.
³ Department of Neurology, International University of Health and Welfare Narita Hospital, Chiba, Japan.
⁴ Department of Neurology, Fukuoka Sanno Hospital, Fukuoka, Japan.
⁵ Department of Orthoptics, Faculty of Medicine, Fukuoka International University of Health and Welfare, Fukuoka, Japan.

Abstract

Background: Alzheimer's disease (AD) is the most common condition of all neurodegenerative diseases and is characterized by various cognitive dysfunctions. Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have revealed the physiological dynamics of functionally connected brain networks, which are called resting-state networks (RSNs). Associations between impairments of RSNs and various neuropsychiatric diseases, such as AD, have been reported. Acetylcholinesterase inhibitors (AChEIs) have been used as a pharmacological treatment for mild-to-moderate moderate AD, and short-term improvements in cognitive functions and RSNs in restricted areas have been reported.

Objective: We aimed to characterize AChEI-related RSN changes by acquiring two sets of rs-fMRI data separated by approximately 3 to 6 months.

Methods: Seventeen patients with AD and nine healthy subjects participated in this study. Independent component analysis was performed on the rs-fMRI data of AChEI-responsive and non-responsive AD patients, stratified according to change in Mini-Mental State Examination (MMSE) scores after 3 to 6 months of AChEI therapy. In addition, a region of interest-based analysis of the rs-fMRI data before therapy was performed to explore the functional connectivity (FC) changes associated with AchEI therapy.

Results: Responders showed a significantly greater increase in MMSE scores, especially for orientation for time, than that of non-responders following AChEI therapy. A subtraction map of MMSE score differences (responders minus non-responders) in the independent component analysis revealed higher FC of the dorsal attention network in responders compared with that in non-responders. Moreover, in the region of interest analysis of untreated status data, the dorsal attention network showed significant negative FC with the right planum temporale, which belongs to the ventral attention network, proportional to MMSE score change.

Conclusion: The negative correlation of the FC of the dorsal attention network and right planum temporale before AChEI therapy and MMSE score change may be a biomarker of the therapeutic effect of AChEIs for AD.

Keywords: Alzheimer’s disease; acetylcholinesterase inhibitors; dorsal attention network; resting-state fMRI; resting-state networks.