Inflection Point in Course of Mild Cognitive Impairment: Increased Functional Connectivity of Default Mode Network

Article type: Research Article

Authors: Tao, Wuhai^{a; b; 1} | Li, Xin^{a; b; 1} | Zhang, Junying^{a; b} | Chen, Yaojing^{a; b} | Ma, Chao^{a; b} | Liu, Zhen^{a; b} | Yang, Caishui^{a; b} | Wang, Wenxiao^{a; b} | Chen, Kewei^{a; c} | Wang, Jun^{a; b; *} | Zhang, Zhanjun^{a; b; *}

Affiliations: [a] State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, P. R. China | [b] BABRI Centre, Beijing Normal University, Beijing, P. R. China | [c] Banner Alzheimer’s Institute, Phoenix, AZ, USA

Correspondence: [*] Correspondence to: Zhanjun Zhang, MD, State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, P. R. China. Tel.: +86 1058802005; Fax: +86 1058802005; E-mail: [email protected] and Jun Wang, PhD, State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, P. R. China. Tel.: +86 1058802005; Fax: +86 1058802005; E-mail: WEML [email protected].

Note: [1] These authors contributed to this work equally.

Abstract: The alteration of the default mode network (DMN) functional connectivity (FC) has been reported in patients with amnestic mild cognitive impairment (aMCI) as a predictor of Alzheimer’s disease (AD). However, no studies exist that examined stage-dependent DMN FC changes throughout the course of aMCI. The present study aims to characterize patterns of DMN FC over three aMCI stages as first defined. Utilizing the extreme groups approach on the performance of memory tasks, aMCI subjects were divided into mild, moderate, and severe stages. Independent component analysis was used to assess DMN for individual patients in each of the three cross-sectionally defined stages. Instead of finding that continued monotonic decline was the case for the hippocampus volume, which we also investigated in this study, we observed an increase in DMN functional connectivity from mild aMCI to moderate aMCI and a decrease to severe aMCI, mainly in the left precuneus and superior parietal lobe. Moreover, the FC was significantly associated with cognitive performance. Though a longitudinal study is needed to confirm these results, our cross-sectional finding is that non-linear FC changes in DMN could be a characteristic of prodromal early disease development.

Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, default mode network, functional connectivity, non-monotomic trajectory

DOI: 10.3233/JAD-170252

Journal: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 679-690, 2017