{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:55:29Z","timestamp":1780433729763,"version":"3.54.1"},"reference-count":17,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"am","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG024904"],"award-info":[{"award-number":["U01 AG024904"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH\u201012\u20102\u20100012"],"award-info":[{"award-number":["W81XWH\u201012\u20102\u20100012"]}],"id":[{"id":"10.13039\/100000005","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":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Clinical Dementia Rating Sum of Boxes (CDR\u2010SB) is a reliable and clinically meaningful composite for assessing treatment effects in Alzheimer's disease (AD) clinical trials. Small CDR\u2010SB differences at the end of a trial often lead to controversy in deriving clinically meaningful interpretations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We estimated progression\u2010free time (PFT) participants remained at each 0.5 unit CDR\u2010SB increment in dominantly inherited AD (DIAD) and sporadic AD populations, evaluating its potential as an alternative measure of treatment effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>PFT is longer at CDR\u2010SB \u2264 2.0 (1\u20132 years) and shorter at CDR\u2010SB \u2265 5 (\u2264 0.33) in the Alzheimer's Disease Neuroimaging Initiative cohort. The DIAD cohort showed similar but shorter times. Using PFT, continuous lecanemab treatment for 3 years is estimated to delay disease progression by 0.62 years in the sporadic population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>PFT provides a benchmark for expressing clinical progression and treatment effects and can be applied particularly during open\u2010label extensions and single\u2010arm trials without placebo comparisons.<\/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>We estimated the progression\u2010free time at each 0.5 unit Clinical Dementia Rating Sum of Boxes increment in dominantly inherited Alzheimer's disease (AD) and sporadic AD populations.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We proposed using progression\u2010free time to estimate treatment effects in open\u2010label extension or single\u2010arm studies.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>If further validated, progression\u2010free time could serve as a benchmark for assessing clinical progression and treatment effects.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70643","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T18:11:24Z","timestamp":1757095884000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical progression on CDR\u2010SB\u00a9: Progression\u2010free time at each 0.5 unit level in dominantly inherited and sporadic Alzheimer's disease populations"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6808-8737","authenticated-orcid":false,"given":"Guoqiao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology Washington University, School of Medicine  St. Louis Missouri USA"},{"name":"Division of Biostatistics Washington University School of Medicine in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University, School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"McDade","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University, School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjie","family":"Xiong","sequence":"additional","affiliation":[{"name":"Division of Biostatistics Washington University School of Medicine in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Hartz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall J.","family":"Bateman","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University, School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University, School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lon S.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and The Behavioral Sciences, Department of Neurology Keck School of Medicine University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer's Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2022.30"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01369-8"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410230509"},{"issue":"1","key":"e_1_2_8_7_1","first-page":"S45","article-title":"Rationale for use of the Clinical Dementia Rating Sum of Boxes as a primary outcome measure for Alzheimer's disease clinical trials","volume":"9","author":"Cedarbaum JM","year":"2013","journal-title":"Alzheimers 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