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This study examined gait across 32 months in relation to neuroimaging biomarkers (amyloid beta [A\u03b2], neurofibrillary tangles [NFTs], and hippocampal volume), cognitive decline, and clinical AD status in adults with DS.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Participants were 218 adults with DS who underwent A\u03b2 and NFT positron emission tomography (PET) and magnetic resonance imaging (MRI) scans, cognitive testing, and gait assessments at baseline and 32 months. Residual change regression models were conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Higher baseline A\u03b2 PET and NFT PET and lower MRI hippocampal volume were associated with gait declines across 32 months. Cognitive declines were associated with gait declines. Participants with clinical dementia at 32 months had greater gait decline than those who were cognitively stable.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Gait impairments are a key feature of DS\u2010associated AD (DSAD). Gait assessments could offer a quick, cost\u2010effective, non\u2010invasive screen for DSAD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Those with clinical status of dementia had lower gait performance than those who were cognitively stable.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Higher baseline amyloid beta and neurofibrillary tangle volume was associated with more gait impairments.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Lower baseline hippocampal volume was associated with more gait impairments.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Greater decline in gait performance was associated with cognitive decline.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Greater decline in gait performance was associated with more dementia symptoms.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70211","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T05:08:03Z","timestamp":1745816883000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Longitudinal investigation of gait and Alzheimer's disease in adults with Down syndrome"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7899-711X","authenticated-orcid":false,"given":"Ashlyn","family":"Barry","sequence":"first","affiliation":[{"name":"Waisman Center University of Wisconsin\u2013Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie C.","family":"Peven","sequence":"additional","affiliation":[{"name":"Behavioral Health Service Line VA Pittsburgh Healthcare System  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin L.","family":"Handen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Bolt","sequence":"additional","affiliation":[{"name":"Waisman Center University of Wisconsin\u2013Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J.","family":"Krinsky\u2010McHale","sequence":"additional","affiliation":[{"name":"New York Institute for Basic Research in Developmental Disabilities Department of Psychology  Staten Island New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy L.","family":"Hom","sequence":"additional","affiliation":[{"name":"Deparment of Psychiatry &amp; Human Behavior University of California, Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel C. 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