The increased effective connectivity from left middle occipital gyrus to right medial septum/diagonal bands in AD patients after donepezil intervention

Ting Yang; Fuquan Wei; Yufei Guo; Mengxiao Zhu; Hongtao Hou; Zhongwei Guo; Xiaozheng Liu

doi:10.3389/fnagi.2024.1362790

The increased effective connectivity from left middle occipital gyrus to right medial septum/diagonal bands in AD patients after donepezil intervention

Front Aging Neurosci. 2024 Apr 10:16:1362790. doi: 10.3389/fnagi.2024.1362790. eCollection 2024.

Authors

Ting Yang¹, Fuquan Wei², Yufei Guo³, Mengxiao Zhu³, Hongtao Hou², Zhongwei Guo², Xiaozheng Liu^{1

4}

Affiliations

¹ The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
² Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
³ The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
⁴ Wenzhou Key Laboratory of Structural and Functional Imaging, Wenzhou, Zhejiang, China.

Abstract

Introduction: Donepezil enhances the function of cholinergic nerves by increasing the concentration of acetylcholine, thereby improving clinical symptoms in patients with Alzheimer's disease (AD). However, the neural mechanisms of how donepezil modulates the effective connectivity (EC) network of cholinergic system in AD patients remain unknown. We speculated that the effective network of the cholinergic system changes in AD patients after donepezil intervention.

Methods: We employed resting-state functional magnetic resonance imaging and Granger causality analysis approach to explore changes in the effective connectivity network of the basal forebrain in AD patients before and after donepezil intervention. This study included 32 participants, including 16 healthy controls (HCs) and 16 AD patients. In a 3T MRI scanner, the 16 AD patients were scanned before and after the donepezil intervention. To compare EC differences between the three groups of participants, ANOVA and post-hoc t-tests analysis were employed.

Results: Compared to baseline status, AD patients after donepezil intervention had an increased EC from left middle occipital gyrus to right medial septum/diagonal bands. Compared to HCs, AD patients after donepezil intervention had an increased EC from right inferior frontal gyrus/orbit part to right medial septum/diagonal bands, AD patients before donepezil intervention had a reduced EC from right precuneus to right medial septum/diagonal bands. A significant positive correlation was found between EC values in right precuneus and Mini-Mental State Examination in pre-intervention AD patients (r = 0.7338, p = 0.0012).

Discussion: Our study showed that effective connectivity of brain regions associated with the default mode network in the cholinergic pathway was enhanced after donepezil intervention. The results of this study will help us to better understand the neural mechanisms of donepezil intervention in AD and to find clinical targets for intervention.

Keywords: Alzheimer’s disease; cholinergic; donepezil; effective connectivity; functional magnetic resonance imaging.

Grants and funding

The authors declare that financial support was received for the research, authorship, and/or publication of this article. This research was supported by the General Project of the Department of Science and Technology of Zhejiang Province (2017KY109 and 2020KY182 to XL) and the General Project of the Department of Science and Technology of Zhejiang Province (2018KY031 and 2024KY873 to ZG).