{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:58:21Z","timestamp":1790675901119,"version":"4.1.0"},"reference-count":33,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K07720"],"award-info":[{"award-number":["21K07720"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K10805"],"award-info":[{"award-number":["24K10805"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Anti-amyloid-\u03b2 (anti-A\u03b2) therapy slows cognitive decline but paradoxically accelerates whole-brain gray matter atrophy, complicating outcome prediction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To identify early imaging markers that predict long-term prognoses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This longitudinal cohort study prospectively enrolled participants with early Alzheimer's disease, initiating anti-A\u03b2 therapy. We performed automated T1-weighted MRI volumetric analysis of the whole-brain gray matter, hippocampus, and white matter hyperintensities (WMH). Temporal dynamics were characterized using piecewise linear regression, and predictive utility was assessed using multivariate linear regression analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-two participants (74\u2009\u00b1\u200911 years; 14 women) were followed for 376\u2009\u00b1\u2009146 days. Significant volume changes occurred in all regions (p\u2009&lt;\u20090.01). No overt amyloid-related edema was detected, and hemorrhagic events were mild to moderate. Piecewise regression revealed an initial WMH surge that decelerated after 60 days (\u03b2=-0.19 [95%CI: \u22120.33, \u22120.042], p\u2009=\u20090.01), whereas gray matter regions showed linear volume decline. Early subthreshold WMH expansion predicted long-term atrophy independent of baseline covariates (age, sex, amyloid burden, mini\u2013mental state examination score, drug, and hemorrhagic events) in the hippocampus (\u03b2=-0.058 [95%CI: \u22120.092, \u22120.025], p\u2009=\u20090.003), and whole-brain gray matter (\u03b2=-0.033 [95%CI: \u22120.065, \u22120.002], p\u2009=\u20090.04). Early whole-brain gray matter atrophy correlated with the WMH surge (\u03b2=-0.53 [95%CI: \u22120.69, \u22120.38], p\u2009&lt;\u20090.001) and predicted long-term hippocampal atrophy (\u03b2=0.098 [95%CI: 0.038, 0.16], p\u2009=\u20090.004).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A transient WMH surge within the first 60 days of therapy mirrors the known time course of amyloid-related imaging abnormalities. Along with concurrent early whole-brain volume loss, this surge independently predicts accelerated long-term hippocampal and whole-brain atrophy, highlighting its potential as an early prognostic imaging marker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261475336","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T17:45:33Z","timestamp":1786211133000},"page":"1099-1109","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Subthreshold early white-matter hyperintensity increase predicts accelerated hippocampal and whole-brain atrophy in anti-amyloid-\u03b2 immunotherapy"],"prefix":"10.1177","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2132-1642","authenticated-orcid":false,"given":"Shiori","family":"Amemiya","sequence":"first","affiliation":[{"name":"The University of Tokyo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7570-924X","authenticated-orcid":false,"given":"Hidemasa","family":"Takao","sequence":"additional","affiliation":[{"name":"The University of Tokyo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoya","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"The University of Tokyo"},{"name":"The University of Tokyo Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Umeda-Kameyama","sequence":"additional","affiliation":[{"name":"The University of Tokyo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Niimi","sequence":"additional","affiliation":[{"name":"The University of Tokyo Hospital"},{"name":"The University of Tokyo Hospital"},{"name":"The University of Tokyo Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1147-9454","authenticated-orcid":false,"given":"Toshiyuki","family":"Kakumoto","sequence":"additional","affiliation":[{"name":"The University of Tokyo Hospital"},{"name":"The University of Tokyo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Satake","sequence":"additional","affiliation":[{"name":"The University of Tokyo Hospital"},{"name":"The University of Tokyo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Mitsui","sequence":"additional","affiliation":[{"name":"The University of Tokyo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumito","family":"Ogawa","sequence":"additional","affiliation":[{"name":"The University of Tokyo"},{"name":"The University of Tokyo Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1180-2629","authenticated-orcid":false,"given":"Osamu","family":"Abe","sequence":"additional","affiliation":[{"name":"The University of Tokyo"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207156"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2022.30"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2100708"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-150448"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.1992.tb01992.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.8.1559"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001219"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2010.03.018"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giae049"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.07.020"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.02.076"},{"key":"e_1_3_3_15_2","first-page":"197","article-title":"Symmetric diffeomorphic modeling of longitudinal structural MRI","volume":"6","author":"Ashburner J","year":"2012","unstructured":"Ashburner J, Ridgway GR. 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