Four Distinct Subtypes of Alzheimer?s Disease Based on Resting-State Connectivity Biomarkers

doi:10.1016/j.biopsych.2022.06.019

	Four Distinct Subtypes of Alzheimer?s Disease Based on Resting-State Connectivity Biomarkers
	Chen, Pindong 17,18,19; Yao, Hongxiang 16; Tijms, Betty M.2; Wang, Pan 8; Wang, Dawei 5; Song, Chengyuan 4; Yang, Hongwei 1; Zhang, Zengqiang 3; Zhao, Kun 13; Qu, Yida 17,18,19
刊名	BIOLOGICAL PSYCHIATRY
	2023-05-01
卷号	93 期号:9 页码:759-769
ISSN号	0006-3223
DOI	10.1016/j.biopsych.2022.06.019
通讯作者	Zhou, Bo(zhoubo@301hospital.com.cn) ; Liu, Yong(yongliu@bupt.edu.cn)
英文摘要	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.
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
WOS关键词	TAU PET PATTERNS ; FUNCTIONAL CONNECTIVITY ; CORTICAL THICKNESS ; DEFINED SUBTYPES ; CLINICAL CHARACTERISTICS ; ASSOCIATION WORKGROUPS ; DIAGNOSTIC GUIDELINES ; CEREBROSPINAL-FLUID ; NATIONAL INSTITUTE ; BRAIN ATROPHY
WOS研究方向	Neurosciences & Neurology ; Psychiatry
语种	英语
出版者	ELSEVIER SCIENCE INC
WOS记录号	WOS:000982090400001
资助机构	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
内容类型	期刊论文
源URL	[http://ir.ia.ac.cn/handle/173211/53426]
专题	自动化研究所_脑网络组研究中心
通讯作者	Zhou, Bo; Liu, Yong
作者单位	1.Capital Med Univ, Xuanwu Hosp, Dept Radiol, Beijing, Peoples R China 2.Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Amsterdam Neurosci, Amsterdam UMC,Locat VUmc,Dept Neurol, Amsterdam, Netherlands 3.Branch Chinese PLA Gen Hosp, Sanya, Peoples R China 4.Shandong Univ, Qilu Hosp, Dept Neurol, Jinan, Peoples R China 5.Shandong Univ, Dept Radiol, Qilu Hosp, Jinan, Peoples R China 6.Tianjin Med Univ Gen Hosp, Dept Radiol, Tianjin, Peoples R China 7.Tianjin Univ, Tianjin Huanhu Hosp, Dept Radiol, Tianjin, Peoples R China 8.Tianjin Univ, Tianjin Huanhu Hosp, Dept Neurol, Tianjin, Peoples R China 9.Beijing Univ Posts & Telecommun, Sch Artificial Intelligence, Beijing, Peoples R China 10.Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China
推荐引用方式 GB/T 7714	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.