{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T05:15:42Z","timestamp":1783314942701,"version":"3.54.6"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NHRI\u2010EX115\u201011531NI"],"award-info":[{"award-number":["NHRI\u2010EX115\u201011531NI"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["MOST 107\u20102314\u2010B\u2010075\u2010014\u2010MY3"],"award-info":[{"award-number":["MOST 107\u20102314\u2010B\u2010075\u2010014\u2010MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 112\u20102314\u2010B\u2010075\u2010034\u2010MY3"],"award-info":[{"award-number":["NSTC 112\u20102314\u2010B\u2010075\u2010034\u2010MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 114\u20102314\u2010B\u2010075\u2010002"],"award-info":[{"award-number":["NSTC 114\u20102314\u2010B\u2010075\u2010002"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 114\u20102314\u2010B\u2010A49\u2010041\u2010MY3"],"award-info":[{"award-number":["NSTC 114\u20102314\u2010B\u2010A49\u2010041\u2010MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011912","name":"Taipei Veterans General Hospital","doi-asserted-by":"publisher","award":["V112C\u2010001"],"award-info":[{"award-number":["V112C\u2010001"]}],"id":[{"id":"10.13039\/501100011912","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011912","name":"Taipei Veterans General Hospital","doi-asserted-by":"publisher","award":["V114C\u2010063"],"award-info":[{"award-number":["V114C\u2010063"]}],"id":[{"id":"10.13039\/501100011912","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":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by cysteine\u2010altering\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      variants. We examined whether neuroimaging\u2010defined brain age is altered in CADASIL and its association with disease severity and outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      A brain\u2010age prediction model was constructed using magnetic resonance imaging from 1482 healthy individuals and applied to 153 individuals with\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      variants and 30 controls. Brain age gap (BAG) was calculated as predicted minus chronological age. Associations between BAG, imaging markers, and clinical outcomes were analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Individuals with\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      variants exhibited significantly higher BAG than controls. Higher BAG was associated with greater disease severity, neuroimaging markers \u2013 most prominently peak width of skeletonized mean diffusivity \u2013 and poorer clinical performance. In addition, BAG showed a partial mediation effect in the association between disease stage and cognitive performance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Accelerated brain aging is evident in CADASIL, and the BAG reflects the cumulative microvascular injury burden and may be involved in the pathophysiological pathway linking disease progression to cognitive impairment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71535","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T03:06:08Z","timestamp":1780455968000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of imaging\u2010defined brain age with disease severity and adverse outcomes in CADASIL"],"prefix":"10.1002","volume":"22","author":[{"given":"Shao\u2010Lun","family":"Hsu","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"Department of Neurology Fu Jen Catholic University Hospital  New Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei\u2010Lin","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun\u2010Hsien","family":"Chou","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"Brain Research Center National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen\u2010Yuan","family":"Kuo","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"Brain Research Center National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching\u2010Po","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"Brain Research Center National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"Department of Education and Research Taipei City Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Chu","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Neurology Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Department of Neurology National Yang Ming Chiao Tung University School of Medicine  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9419-9070","authenticated-orcid":false,"given":"Chih\u2010Ping","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Neurology Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Department of Neurology National Yang Ming Chiao Tung University School of Medicine  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Chung","family":"Lee","sequence":"additional","affiliation":[{"name":"Brain Research Center National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"Department of Neurology Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Department of Neurology National Yang Ming Chiao Tung University School of Medicine  Taipei Taiwan"},{"name":"Center for Intelligent Drug Systems and Smart Bio\u2010devices (IDS2B) National Yang Ming Chiao Tung University  Hsinchu Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70127-9"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2015.17.1.7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00131-X"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209310"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2024.4487"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2025.1573052"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.876437"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X221126280"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200744"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.122.039325"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.05.039"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2017.10.001"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.626677"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.11.005"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43856-025-01100-5"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.patter.2023.100712"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaf109"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.30109"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.70048"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcac233"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.70094"},{"key":"e_1_2_8_23_1","first-page":"676","article-title":"Factor structure and explanatory variables of the Mini\u2010Mental State Examination (MMSE) for elderly persons in Taiwan","volume":"100","author":"Shyu YI","year":"2001","journal-title":"J Formos Med Assoc"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.15135"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12165170"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000258355.23810.c6"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.06.017"},{"key":"e_1_2_8_28_1","first-page":"7867","article-title":"Ordinal classification with distance regularization for robust brain age prediction","volume":"2024","author":"Shah J","year":"2024","journal-title":"IEEE Winter Conf Appl Comput Vis"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-020-00260-3"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004150050189"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcab107"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.104135"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70013-4"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11604-017-0617-z"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24758"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2020.102229"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac486"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcae382"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0446-9"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000216271.96364.50"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10194-012-0418-9"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2020.135388"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0014-y"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001502"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2005.068726"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200805"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-022-00219-7"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-025-01232-4"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2022.10.007"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103600"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.03.014"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18037-z"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.71535","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.71535","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.71535","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T04:41:47Z","timestamp":1783312907000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.71535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":51,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/alz.71535"],"URL":"https:\/\/doi.org\/10.1002\/alz.71535","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2026-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71535"}}