An Inverse U-Shaped Curve of Resting-State Networks in Individuals at High Risk of Alzheimer's Disease

• Published in: The journal of clinical psychiatry Vol. 79; no. 2
• Main Authors: Ye, Qing, Chen, Haifeng, Su, Fan, Shu, Hao, Gong, Liang, Xie, Chunming, Zhou, Hong, Bai, Feng
• Format: Journal Article
• Language: English
• Published: United States 01.03.2018
• Subjects: Aged; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - physiopathology; Amnesia - diagnostic imaging; Amnesia - physiopathology; Apolipoprotein E4 - genetics; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - physiopathology; Cognitive Dysfunction - diagnostic imaging; Cognitive Dysfunction - physiopathology; Connectome - methods; Cross-Sectional Studies; Disease Progression; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Net - diagnostic imaging; Nerve Net - physiopathology; Risk
• ISSN: 1555-2101
• DOI: 10.4088/JCP.17m11583

Higher functional connectivity (FC) in resting-state networks has been shown in individuals at risk of Alzheimer's disease (AD) by many studies. However, the longitudinal trajectories of the FC remain unknown. The present 35-month follow-up study aimed to explore longitudinal changes in higher FC in multiple resting-state networks in subjects with the apolipoprotein E ε4 allele (ApoE4) and/or amnestic mild cognitive impairment (aMCI). Fifty-one subjects with aMCI and 64 cognitively normal (CN) subjects underwent neuropsychological tests and resting-state functional magnetic resonance imaging (fMRI) scans twice from April 2011 to June 2015. Subjects were divided into 4 groups according to diagnosis and ApoE4 status. The CN non-ApoE4 group served as a control group, and other groups served as AD risk groups. The cross-sectional and longitudinal patterns of multiple resting-state networks, including default mode network, hippocampus network, executive control network, and salience network, were explored by comparing FC data between groups and between time points, respectively. At baseline, compared with the control group, the AD risk groups showed higher FC with 8 regions in multiple networks. At follow-up, 6 of the regions displayed longitudinally decreased FC in AD risk groups. In contrast, the FC with all of these regions was maintained in the control group. Notably, among the 3 risk groups, most of the higher FC at baseline (5 of the 8 regions) and longitudinally decreased FC at follow-up (4 of the 6 regions) were shown in the aMCI ApoE4 group. Higher resting-state FC is followed by a decline in subjects at AD risk, and this inverse U-shaped trajectory is more notable in subjects with higher risk.