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However, it is unknown whether their coexistence is associated with poorer cognitive performance and its underlying mechanism in neurodegenerative diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Gait speed, <jats:italic>APOE<\/jats:italic> E4, cognition, and neuroimaging were assessed in 480 older adults with neurodegeneration. Participants were grouped by <jats:italic>APOE<\/jats:italic> E4 presence and slow gait. Mediation analyses were conducted to determine if brain structures could explain the link between these factors and cognitive performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p><jats:italic>APOE<\/jats:italic> E4 carriers with slow gait had the lowest global cognitive performance and smaller gray matter volumes compared to non\u2010<jats:italic>APOE<\/jats:italic> E4 carriers with normal gait. Coexistence of <jats:italic>APOE<\/jats:italic> E4 and slow gait best predicted global and domain\u2010specific poorer cognitive performances, mediated by smaller gray matter volume.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Gait slowness in <jats:italic>APOE<\/jats:italic> E4 carriers with neurodegenerative diseases may indicate extensive gray matter changes associated with poor cognition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:italic>APOE<\/jats:italic> E4 and slow gait are risk factors for cognitive decline in neurodegenerative diseases.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Slow gait and smaller gray matter volumes are associated, independently of <jats:italic>APOE<\/jats:italic> E4.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Worse cognition in <jats:italic>APOE<\/jats:italic> E4 carriers with slow gait is explained by smaller GM volume.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Gait slowness in <jats:italic>APOE<\/jats:italic> E4 carriers indicates poorer cognition\u2010related brain changes.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13740","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T07:04:59Z","timestamp":1710227099000},"page":"2968-2979","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Link among <i>apolipoprotein E<\/i> E4, gait, and cognition in neurodegenerative diseases: ONDRI study"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3475-9686","authenticated-orcid":false,"given":"Ryota","family":"Sakurai","sequence":"first","affiliation":[{"name":"Research Team for Social Participation and Healthy Aging Tokyo Metropolitan Institute for Geriatrics and Gerontology  Itabashi\u2010ku Tokyo Japan"},{"name":"Gait &amp; Brain Lab, St. Joseph' Health Care London, Lawson Health Research, Western University, Division of Geriatric Medicine London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7659-4285","authenticated-orcid":false,"given":"Frederico","family":"Pieruccini\u2010Faria","sequence":"additional","affiliation":[{"name":"Gait &amp; Brain Lab, St. Joseph' Health Care London, Lawson Health Research, Western University, Division of Geriatric Medicine London Ontario Canada"},{"name":"Department of Medicine Division of Geriatric Medicine Parkwood Hospital Western University, Parkwood Institute  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0367-0654","authenticated-orcid":false,"given":"Benjamin","family":"Cornish","sequence":"additional","affiliation":[{"name":"Neuroscience, Mobility and Balance Lab, Department of Kinesiology and Health Sciences University of Waterloo  Waterloo Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Fraser","sequence":"additional","affiliation":[{"name":"Neuroscience, Mobility and Balance Lab, Department of Kinesiology and Health Sciences University of Waterloo  Waterloo Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9998-6612","authenticated-orcid":false,"given":"Malcolm A.","family":"Binns","sequence":"additional","affiliation":[{"name":"Rotman Research Institute, Baycrest Health Sciences  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6118-4366","authenticated-orcid":false,"given":"Derek","family":"Beaton","sequence":"additional","affiliation":[{"name":"Data Science and Advanced Analytics, St. Michael's Hospital, Unity Health Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3863-9304","authenticated-orcid":false,"given":"Allison Ann","family":"Dilliott","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Montreal Neurological Institute, McGill University  Montr\u00e9al Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5161-203X","authenticated-orcid":false,"given":"Donna","family":"Kwan","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience Studies, Queen's University  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5582-1776","authenticated-orcid":false,"given":"Joel","family":"Ramirez","sequence":"additional","affiliation":[{"name":"L.C. 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