{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:17:06Z","timestamp":1785417426567,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,24]]},"group-title":"Neurology","reference-count":17,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["JP24dk0207068"],"award-info":[{"award-number":["JP24dk0207068"]}],"id":[{"id":"https:\/\/ror.org\/004rtk039","id-type":"ROR","asserted-by":"publisher"}]},{"award":["JP25dk0207075"],"award-info":[{"award-number":["JP25dk0207075"]}],"id":[{"id":"https:\/\/ror.org\/004rtk039","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["JP24K10653"],"award-info":[{"award-number":["JP24K10653"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["JP25K19014"],"award-info":[{"award-number":["JP25K19014"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>INTRODUCTION<\/jats:title>\n                  <jats:p>The Clinical Dementia Rating Sum of Boxes (CDR-SB), a primary outcome in anti-amyloid therapy (AAT) trials, integrates information from participants and study partners. CDR-SB scores may vary by study partner characteristics, but their impact on 18-month change interpretation remains unclear.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>Using the NACC Uniform Data Set, we fitted linear mixed-effects calibration models in an Alzheimer\u2019s disease (AD)-primary early symptomatic cohort and propagated study partner-associated coefficients through Monte Carlo simulations. We estimated components of 18-month CDR-SB change under observed profile changes, simulated follow-up imbalance in a common female living-with profile, and tipping-point scenarios. Analyses were repeated in amyloid-positive and trial-like cohorts.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>The AD-primary cohort included 15,061 participants and 7,683 baseline-to-18-month pairs. Observed profile changes generated a negligible cohort-level component (mean 0.0014 points, 95% simulation interval 0.0006 to 0.0022). Simulated follow-up imbalance generated differences of 0.014 to 0.071 points across 10% to 50% reassignment. Under the primary calibration model, generating a 0.45-point difference, equal to the reported Clarity AD CDR-SB group difference, required median net imbalance &gt;100% and was feasible in 48% of iterations. Amyloid-positive and trial-like cohorts had lower median tipping points but wider intervals, reflecting coefficient imprecision.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DISCUSSION<\/jats:title>\n                  <jats:p>In the large AD-primary cohort, observed study partner profile changes and simulated follow-up imbalance generated CDR-SB differences that were small relative to the 0.45-point Clarity AD benchmark. Biomarker-confirmed estimates were less stable because of coefficient imprecision. These findings suggest limited impact under typical AD-primary conditions but support systematic study partner profile collection and sensitivity analyses in observational and external-comparator CDR-SB studies for AAT evaluation.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.22.26356066","type":"posted-content","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T03:15:19Z","timestamp":1782357319000},"source":"Crossref","is-referenced-by-count":0,"title":["Study partner profile effects on CDR-SB change in anti-amyloid therapy evaluation"],"prefix":"10.64898","author":[{"given":"Ambre","family":"Mouni\u00e9","sequence":"first","affiliation":[{"name":"Dementia Inclusion and Therapeutics, The University of Tokyo Hospital, Tokyo, Japan"},{"name":"Cognitive Sciences, Universit\u00e9 C\u00f4te d\u2019Azur, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichiro","family":"Sato","sequence":"additional","affiliation":[{"name":"Dementia Inclusion and Therapeutics, The University of Tokyo Hospital, Tokyo, Japan"},{"name":"Unit for Early and Exploratory Clinical Development, The University of Tokyo Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Dementia Inclusion and Therapeutics, The University of Tokyo Hospital, Tokyo, Japan"},{"name":"Unit for Early and Exploratory Clinical Development, The University of Tokyo Hospital, Tokyo, Japan"},{"name":"Department of Neurology, The University of Tokyo Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Niimi","sequence":"additional","affiliation":[{"name":"Dementia Inclusion and Therapeutics, The University of Tokyo Hospital, Tokyo, Japan"},{"name":"Unit for Early and Exploratory Clinical Development, The University of Tokyo Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Iwatsubo","sequence":"additional","affiliation":[{"name":"Dementia Inclusion and Therapeutics, The University of Tokyo Hospital, Tokyo, Japan"},{"name":"Unit for Early and Exploratory Clinical Development, The University of Tokyo Hospital, Tokyo, Japan"},{"name":"National Center of Neurology and Psychiatry, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026062608330859000_2026.06.22.26356066v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2026.101609"},{"key":"2026062608330859000_2026.06.22.26356066v1.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"2026062608330859000_2026.06.22.26356066v1.3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"2026062608330859000_2026.06.22.26356066v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.11.002"},{"key":"2026062608330859000_2026.06.22.26356066v1.5","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.11.2412-a"},{"key":"2026062608330859000_2026.06.22.26356066v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.01.005"},{"key":"2026062608330859000_2026.06.22.26356066v1.7","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12439"},{"key":"2026062608330859000_2026.06.22.26356066v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00732-x"},{"key":"2026062608330859000_2026.06.22.26356066v1.9","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-131052"},{"key":"2026062608330859000_2026.06.22.26356066v1.10","unstructured":"Alzheimer\u2019s Network for Treatment and Diagnostics (ALZ-NET). 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