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Four Distinct Subtypes of Alzheimer's Disease Based on Resting-State Connectivity Biomarkers
Chen, Pindong1,2; Yao, Hongxiang3; Tijms, Betty M.4; Wang, Pan5; Wang, Dawei6; Song, Chengyuan7; Yang, Hongwei8; Zhang, Zengqiang9; Zhao, Kun10; Qu, Yida1,2; Kang, Xiaopeng1,2; Du, Kai1,2; Fan, Lingzhong1; Han, Tong11; Yu, Chunshui12; Zhang, Xi13; Jiang, Tianzi1,2; Zhou, Yuying5; Lu, Jie8; Han, Ying14,15,16; Liu, Bing17; Zhou, Bo13; Liu, Yong1,2,18
发表期刊BIOLOGICAL PSYCHIATRY
ISSN0006-3223
2023-05-01
卷号93期号:9页码:759-769
摘要

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder with significant heterogeneity. Different AD phenotypes may be associated with specific brain network changes. Uncovering disease heterogeneity by using functional networks could provide insights into precise diagnoses. METHODS: We investigated the subtypes of AD using nonnegative matrix factorization clustering on the previously identified 216 resting-state functional connectivities that differed between AD and normal control subjects. We conducted the analysis using a discovery dataset (n = 809) and a validated dataset (n = 291). Next, we grouped individuals with mild cognitive impairment according to the model obtained in the AD groups. Finally, the clinical measures and brain structural characteristics were compared among the subtypes to assess their relationship with differences in the functional network. RESULTS: Individuals with AD were clustered into 4 subtypes reproducibly, which included those with 1) diffuse and mild functional connectivity disruption (subtype 1), 2) predominantly decreased connectivity in the default mode network accompanied by an increase in the prefrontal circuit (subtype 2), 3) predominantly decreased connectivity in the anterior cingulate cortex accompanied by an increase in prefrontal cortex connectivity (subtype 3), and 4) pre-dominantly decreased connectivity in the basal ganglia accompanied by an increase in prefrontal cortex connectivity (subtype 4). In addition to these differences in functional connectivity, differences between the AD subtypes were found in cognition, structural measures, and cognitive decline patterns. CONCLUSIONS: These comprehensive results offer new insights that may advance precision medicine for AD and facilitate strategies for future clinical trials.

DOI10.1016/j.biopsych.2022.06.019
关键词[WOS]TAU PET PATTERNS ; FUNCTIONAL CONNECTIVITY ; CORTICAL THICKNESS ; DEFINED SUBTYPES ; CLINICAL CHARACTERISTICS ; ASSOCIATION WORKGROUPS ; DIAGNOSTIC GUIDELINES ; CEREBROSPINAL-FLUID ; NATIONAL INSTITUTE ; BRAIN ATROPHY
收录类别SCI
语种英语
资助项目Fundamental Research Funds for the Central Universities[2021XD-A03-1] ; Beijing Natural Science Funds for Distinguished Young Scholars[JQ20036] ; National Natural Science Foundation of China[81571062] ; National Natural Science Foundation of China[81400890] ; National Natural Science Foundation of China[81471120] ; National Natural Science Foundation of China[W81XWH-12-2-0012] ; Special Fund for Military Health committee[81901101] ; ADNI (National Institutes of Health)[61633018] ; DOD ADNI~ (Department of Defense) ; National Institute on Aging ; National Institute of Biomedical Imaging and Bioengineering ; DNI clinical sites in Canada
项目资助者Fundamental Research Funds for the Central Universities ; Beijing Natural Science Funds for Distinguished Young Scholars ; National Natural Science Foundation of China ; Special Fund for Military Health committee ; ADNI (National Institutes of Health) ; DOD ADNI~ (Department of Defense) ; National Institute on Aging ; National Institute of Biomedical Imaging and Bioengineering ; DNI clinical sites in Canada
WOS研究方向Neurosciences & Neurology ; Psychiatry
WOS类目Neurosciences ; Psychiatry
WOS记录号WOS:000982090400001
出版者ELSEVIER SCIENCE INC
七大方向——子方向分类脑网络分析
国重实验室规划方向分类其他
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被引频次:22[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ia.ac.cn/handle/173211/53427
专题脑图谱与类脑智能实验室_脑网络组研究
通讯作者Zhou, Bo; Liu, Yong
作者单位1.Brainnetome Center & National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China
2.School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, China
3.Department of Radiology, the Second Medical Centre, National Clinical Research Centre for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
4.Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC - Location VUmc, The Netherlands
5.Department of Neurology, Tianjin Huanhu Hospital Tianjin University, Tianjin, China
6.Department of Radiology, Qilu Hospital of Shandong University, Ji'nan, China
7.Department of Neurology, Qilu Hospital of Shandong University, Ji'nan, China
8.Department of Radiology, Xuanwu Hospital of Capital Medical University, Beijing, China
9.Branch of Chinese PLA General Hospital, Sanya, China
10.Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science & Medical Engineering, Beihang University, Beijing, China
11.Department of Radiology, Tianjin Huanhu Hospital, Tianjin, China
12.Department of Radiology, Tianjin Medical University General Hospital, Tianjin, China
13.Department of Neurology, the Second Medical Centre, National Clinical Research Centre for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
14.Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China
15.Beijing Institute of Geriatrics, Beijing, China
16.National Clinical Research Center for Geriatric Disorders, Beijing, China
17.State Key Laboratory of Cognition Neuroscience & Learning, Beijing Normal University, Beijing, China
18.School of Artificial Intelligence, Beijing University of Posts and Telecommunications, Beijing, China
19.Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Amsterdam Neurosci, Amsterdam UMC,Locat VUmc,Dept Neurol, Amsterdam, Netherlands
第一作者单位模式识别国家重点实验室
通讯作者单位模式识别国家重点实验室
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Chen, Pindong,Yao, Hongxiang,Tijms, Betty M.,et al. Four Distinct Subtypes of Alzheimer's Disease Based on Resting-State Connectivity Biomarkers[J]. BIOLOGICAL PSYCHIATRY,2023,93(9):759-769.
APA Chen, Pindong.,Yao, Hongxiang.,Tijms, Betty M..,Wang, Pan.,Wang, Dawei.,...&Liu, Yong.(2023).Four Distinct Subtypes of Alzheimer's Disease Based on Resting-State Connectivity Biomarkers.BIOLOGICAL PSYCHIATRY,93(9),759-769.
MLA Chen, Pindong,et al."Four Distinct Subtypes of Alzheimer's Disease Based on Resting-State Connectivity Biomarkers".BIOLOGICAL PSYCHIATRY 93.9(2023):759-769.
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