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Participants underwent magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET), deriving volumetric and amyloid burden, respectively. Nonlinear associations between regional volumes and estimated years to clinical symptom onset (EYO) were evaluated using generalized additive mixed\u2010models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Longitudinal data from 267 controls, 341 participants with DS, and 358 participants with ADAD were included, totaling 1908 scans. DS volumes were lower than ADAD and controls initially and dropped linearly. ADAD had similar volumes to controls until diverging, beginning at EYO \u20107. Amyloid was negatively associated with volume, with similar slopes in DS and ADAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>ADAD and DS demonstrate distinct patterns of brain volume decline prior to symptom onset despite being similarly affected by amyloid.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71103","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T05:13:02Z","timestamp":1768799582000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Brain volume trajectories in Down syndrome and autosomal dominant Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"James T.","family":"Kennedy","sequence":"first","affiliation":[{"name":"Department of Neurology Washington University School of Medicine in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie K.","family":"Wisch","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna H.","family":"Boerwinkle","sequence":"additional","affiliation":[{"name":"McGovern Medical School University of Texas in Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Millar","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole S.","family":"McKay","sequence":"additional","affiliation":[{"name":"Department of Radiology Washington University School of Medicine in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Brickman","sequence":"additional","affiliation":[{"name":"Department of Neurology Columbia University  New York New York USA"},{"name":"Gertrude H. 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