Affiliations: [a] Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China
| [b] Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China
| [c] Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China
| [d] Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing, China
| [e] Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China
Correspondence:
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Correspondence to: Jianping Jia, Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University. 45 Changchun Street, Xicheng District, Beijing, 100053 China. Tel.: +86 10 83199449. E-mails: [email protected]; [email protected].
Note: [1] These authors contributed equally to this work.
Abstract: Background:The default mode network (DMN) could be divided into subsystems, the functional connectivity of which are different across the Alzheimer’s disease (AD) spectrum. However, the functional connectivity patterns within the subsystems are unknown in presymptomatic autosomal dominant AD (ADAD). Objective:To investigate functional connectivity patterns within the subsystems of the DMN in presymptomatic subjects carrying PSEN1, PSEN2, or APP gene mutations. Methods:Twenty-six presymptomatic mutation carriers (PMC) and twenty-nine cognitively normal non-carriers as normal controls (NC) from the same families underwent resting state functional MRI and structural MRI. Seed-based analyses were done to obtain functional connectivity of posterior and anterior DMN. For the regions that showed significant connectivity difference between PMC and NC, volumes were extracted and compared between the two groups. Connectivity measures were then correlated with cognitive tests scores. Results:The posterior DMN showed connectivity decrease in the PMC group as compared with the NC group, which was primarily the connectivity of left precuneus with right precuneus and superior frontal gyrus; the anterior DMN showed significant connectivity decrease in the PMC group, which was the connectivity of medial frontal gyrus with middle frontal gyrus. In the brain regions showing connectivity changes in the PMC group, there was no group difference in volume. A positive correlation was observed between the precuneus connectivity value and Mini-Mental State Examination total score. Conclusion:Functional connectivity within both posterior and anterior DMN were disrupted in the presymptomatic stage of ADAD. Connectivity disruption within the posterior DMN may be useful for early identification of general cognitive decline and a potential imaging biomarker for early diagnosis.
