{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:28:56Z","timestamp":1791919736959,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No.82471926"],"award-info":[{"award-number":["No.82471926"]}],"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":["No.81901706"],"award-info":[{"award-number":["No.81901706"]}],"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":["No.82171271"],"award-info":[{"award-number":["No.82171271"]}],"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":["A&amp;amp;D Transl Res &amp;amp; Clin Interv"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      Chronic cerebral hypoperfusion (CCH)\u2010induced white matter hyperintensities (WMHs) are a well\u2010established risk factor for cognitive impairment and dementia. While animal and\n                      <jats:italic>post mortem<\/jats:italic>\n                      studies suggest that myelin loss in normal\u2010appearing white matter (NAWM) precedes WMHs, in vivo evidence in human brain remains limited. We aimed to investigate the associations between myelin changes in NAWM, CCH, and cognitive function in patients with moyamoya disease (MMD, a human model of CCH).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We included 58 patients with MMD and 36 healthy controls, and all participants underwent 3.0T magnetic resonance imaging (MRI) with T1\u2010weighted, T2\u2010weighted, and arterial spin labeling (ASL) sequences. Myelin was assessed by the T1\u2010weighted\/T2\u2010weighted ratio (rT1\/T2), and cerebral blood flow (CBF) in each arterial region was measured by ASL. Cognitive function was evaluated using the Mini\u2010Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Patients exhibited decreased rT1\/T2 at lower percentiles (P5 and P10) and increased rT1\/T2 at higher percentiles (P75, P90, and P95) in NAWM (false discovery rate [FDR]\u2010corrected\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.005), along with reduced CBF in the region of anterior circulation (FDR\u2010corrected\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). Voxel\u2010based analysis of NAWM showed region\u2010specific decreases and increases in rT1\/T2 in MMD. The percentile ranges (P90\u2010P10 and P95\u2010P5) of rT1\/T2 showed high accuracy in differentiating patients from controls (accuracy: 88% to 90%). Multivariate analysis further revealed that in patients, both P5 and P10 of rT1\/T2 were significantly associated with reduced CBF in the anterior circulation region (standardized\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 0.318,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.016 and standardized\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a00.267,\u00a0\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.043), and P5 of rT1\/T2 significantly correlated with MMSE and MoCA (standardized\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 0.332,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.004 and standardized\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a00.260,\u00a0\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.011).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our study provides in vivo evidence that CCH induces both myelin loss and potential plastic adaptations in NAWM, with severe myelin loss being associated with cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>MMD features CCH and cognitive decline.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Decreased rT1\/T2 (myelin loss) in NAWM was detected in MMD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The lower percentage of rT1\/T2 correlated with CCH.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The lowest percentage of rT1\/T2 correlated with cognitive decline.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The rT1\/T2 showed high accuracy in differentiating patients from controls.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70164","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T01:24:29Z","timestamp":1760405069000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Chronic cerebral hypoperfusion\u2010induced myelin loss in normal\u2010appearing white matter correlates with cognitive decline: insights from moyamoya disease"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6024-8591","authenticated-orcid":false,"given":"Xinfeng","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Radiology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwen","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0145-7558","authenticated-orcid":false,"given":"Minming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second 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