{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:16:04Z","timestamp":1792203364905,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62206165"],"award-info":[{"award-number":["62206165"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62376150"],"award-info":[{"award-number":["62376150"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82020108013"],"award-info":[{"award-number":["82020108013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272039"],"award-info":[{"award-number":["82272039"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82021002"],"award-info":[{"award-number":["82021002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971641"],"award-info":[{"award-number":["81971641"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001773"],"award-info":[{"award-number":["82001773"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82327809"],"award-info":[{"award-number":["82327809"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Subjective cognitive decline (SCD) has been recognized as a potential risk stage for progression to Alzheimer's disease (AD), while glymphatic dysfunction is considered an important characteristic of AD. We hypothesize that glymphatic dysfunction occurs during the SCD stage, aiming to discover potential biomarkers for SCD.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Participants from two independent studies, Sino Longitudinal Study on Cognitive Decline (SILCODE, <jats:italic>n<\/jats:italic>\u00a0=\u00a0654) and the Alzheimer's Disease Neuroimaging Initiative (ADNI, <jats:italic>n<\/jats:italic>\u00a0=\u00a0650), representing different ethnicities and disease stages, were included to assess glymphatic function using diffusion tensor image analysis along the perivascular space (DTI\u2010ALPS).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Abnormal glymphatic function occurs during the SCD stage, with the ALPS index demonstrating excellent classification performance for SCD and normal controls (area under the receiver operating characteristic curve [AUC]<jats:sub>SILCODE<\/jats:sub>\u00a0=\u00a00.816, AUC<jats:sub>ADNI<\/jats:sub>\u00a0=\u00a00.797). Lower ALPS index indicates higher risk of cognitive progression, which is negatively correlated with Subjective Cognitive Decline Questionnaire 9 scores and amyloid positron emission tomography burden.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISSCUSION<\/jats:title><jats:p>Our study suggests the ALPS index has the potential to serve as a biomarker for SCD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Glymphatic function characterized by the analysis along the perivascular space (ALPS) index becomes abnormal in subjective cognitive decline (SCD), the earliest symptomatic manifestation and preclinical stage of Alzheimer's disease (AD).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The ALPS index demonstrates excellent classification performance for SCD and normal controls in the East Asian and Western cohorts.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Participants with a lower ALPS index show a higher risk of clinical progression.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The ALPS index is closely associated with serval cognitive scales and amyloid beta burden.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14149","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T01:25:23Z","timestamp":1722993923000},"page":"6542-6555","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Impaired glymphatic function as a biomarker for subjective cognitive decline: An exploratory dual cohort study"],"prefix":"10.1002","volume":"20","author":[{"given":"Yuxia","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology Tangshan Central Hospital  Tangshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyao","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering School of Life Science Shanghai University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Zhong","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering School of Life Science Shanghai University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanyu","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Communication and Information Engineering Shanghai University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurology Xuanwu Hospital of Capital Medical University  Beijing China"},{"name":"Center of Alzheimer's Disease Beijing Institute for Brain Disorders  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Alzheimer's Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8856-7217","authenticated-orcid":false,"given":"Chuantao","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine &amp; PET Center Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4948-3683","authenticated-orcid":false,"given":"Jiehui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering School of Life Science Shanghai University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Dementia: World Health Organization (WHO).World Health Organization.2021. Accessed January 15 2023.https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/dementi"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010clinpsy\u2010032816\u2010045136"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(19)30368\u20100"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afy193"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1370\/afm.2443"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(20)32205\u20104"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43657\u2010022\u201000068\u20109"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101544"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003748"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.04.003"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa179"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb8739"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26516"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1222857"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010024\u201001407\u2010w"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13789"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000201300"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen\u20102018\u2010028188"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.01.001"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010190501"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010140276"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11604\u2010021\u201001187\u20105"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11604\u2010017\u20100617\u2010z"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2023.0321\u20102"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxj037"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.08.047"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(13)70044\u20109"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.111.090340"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010190446"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.101911"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330\u2010023\u201010122\u20103"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.08.024"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010020\u201000618\u20101"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010220534"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2016.05.015"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010022\u201000999\u20105"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.14149","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T21:06:43Z","timestamp":1759957603000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.14149"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,6]]},"references-count":38,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/alz.14149"],"URL":"https:\/\/doi.org\/10.1002\/alz.14149","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,6]]},"assertion":[{"value":"2024-04-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}