{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T13:48:51Z","timestamp":1770299331828,"version":"3.49.0"},"posted":{"date-parts":[[2025,5,2]]},"group-title":"Geriatric Medicine","reference-count":62,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>INTRODUCTION<\/jats:title>\n                  <jats:p>This study uses longitudinal amyloid biomarker and cognitive data to generate sample size estimates for two-armed, pre-clinical amyloid clearance clinical trials.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>PET PiB DVR ranges defined three amyloid groups (positive, \u201cA+\u201d; sub threshold\/low positive, \u201csubA+\u201d; and negative, \u201cA-\u201d) in cognitively unimpaired Wisconsin Registry for Alzheimer\u2019s Prevention participants. Amyloid group trajectories estimated from mixed effects models informed per-treatment-arm sample size estimates to detect plausible treatment effects over 3-year (biomarker) or 6-year (cognition) study windows (80% power).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>To detect \u226560% slowing in PiB accumulation, \u226440 may be needed per arm for both SubA+ and A+; to detect the same effect sizes in plasma p-tau217 trajectories, \u223c50-1700 are needed, depending on assay and amyloid subgroup. Among cognitive outcomes, Digit Symbol Substitution and a 5-test Preclinical Alzheimer\u2019s Cognitive Composite consistently required fewest (&lt;2000) per arm.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DISCUSSION<\/jats:title>\n                  <jats:p>Early intervention study planning will benefit from selection of outcomes that are most sensitive to AD biomarker-related preclinical change.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.05.01.25326668","type":"posted-content","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T17:55:17Z","timestamp":1746208517000},"source":"Crossref","is-referenced-by-count":1,"title":["Use of preclinical Alzheimer\u2019s disease trajectories for clinical trial design"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0025-744X","authenticated-orcid":false,"given":"Rebecca E.","family":"Langhough","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek L.","family":"Norton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karly A.","family":"Cody","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lianlian","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin M.","family":"Jonaitis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachael","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramiro Eduardo","family":"Rea Reyes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce P.","family":"Hermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sterling C.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"1","key":"2025050511151065000_2025.05.01.25326668v1.1","doi-asserted-by":"crossref","first-page":"e12360","DOI":"10.1002\/dad2.12360","article-title":"Trajectory of clinical symptoms in relation to amyloid chronicity","volume":"14","year":"2022","journal-title":"Alzheimers Dement (Amst)"},{"key":"2025050511151065000_2025.05.01.25326668v1.2","doi-asserted-by":"crossref","unstructured":"Caselli RJ , Langlais BT , Dueck AC , Chen Y , Su Y , Locke DEC , et al. 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