{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:30:06Z","timestamp":1790357406190,"version":"4.1.0"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute on Aging and the National Institute for Child Health and Human Development","award":["U01 AG051406"],"award-info":[{"award-number":["U01 AG051406"]}]},{"name":"National Institute for Child Health and Human Development","award":["T32 HD007489"],"award-info":[{"award-number":["T32 HD007489"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Alzheimer\u2019s Disease Research Centers Program","award":["P50 AG008702"],"award-info":[{"award-number":["P50 AG008702"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"name":"Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program","award":["U54 HD090256"],"award-info":[{"award-number":["U54 HD090256"]}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001873"],"award-info":[{"award-number":["UL1 TR001873"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]},{"name":"National Centralized Repository for Alzheimer Disease and Related Dementias","award":["U24 AG21886"],"award-info":[{"award-number":["U24 AG21886"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurodevelop Disord"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Adults with Down syndrome (DS) have a 90% lifetime risk for Alzheimer\u2019s disease (AD), with neurobiological pathology present decades prior to dementia onset. The profile and timing of cognitive decline in DS is well-documented. However, there is a small body of research on whether Behavioral and Psychological Symptoms of Dementia (BPSD) occur early on in the progression of AD in DS and are associated with early AD pathology (i.e., amyloid-beta [A\u03b2] and neurofibrillary tau tangles [NFT]).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Data were analyzed from 337 adults with DS (<jats:italic>M<\/jats:italic>\u2009=\u200945.13\u00a0years, <jats:italic>SD<\/jats:italic>\u2009=\u20099.53\u00a0years) enrolled in a large cohort study. The Reiss Screen for Maladaptive Behavior (RSMB) measured common behaviors reported in BPSD across up to four study cycles (spaced approximately 16\u00a0months apart). Linear mixed models estimated change in BPSD as predicted by baseline (a) dementia status (i.e., cognitively stable, mild cognitive impairment [MCI], or dementia), (b) A\u03b2 positron emission tomography (PET) tracer [<jats:sup>11<\/jats:sup>C] PiB, and (c) NFT PET tracer [<jats:sup>18<\/jats:sup>F]AV-1451. Models controlled for chronological age, sex, study site, premorbid intellectual disability level, APOE e4 allele carrier status, psychiatric diagnoses, and psychiatric medication use.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Compared to cognitively stable participants, participants whose status was MCI or dementia, had significantly higher baseline RSMB subdomain scores. Increases in RSMB Depression-Behavioral, Depression-Physical, and Psychosis were observed for participants with MCI. Higher baseline A\u03b2 and NFT were associated with higher RSMB Avoidant at baseline, and increases in RSMB Depression-Physical and Psychosis over time.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>BPSD are an important part of AD in DS, particularly during the prodromal stage. Elevated A\u03b2 and NFT predict higher initial avoidance and change in physical depression behaviors and may indicate MCI in adults with DS. Broader increases in BPSD are observed as adults with DS progress from early to late-stage dementia. Clinicians should rule out other possible causes of BPSD when screening for AD, such as stressful life experiences or co-occurring medical conditions. Caregivers of adults with DS should have resources on BPSD management and self-care strategies.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s11689-025-09604-w","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T05:43:51Z","timestamp":1744350231000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Behavioral and psychological symptoms of dementia and Alzheimer\u2019s disease progression in Down syndrome"],"prefix":"10.1186","volume":"17","author":[{"given":"Melissa R.","family":"Jenkins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie C.","family":"Peven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Kubic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin L.","family":"Handen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J.","family":"Krinsky-McHale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy L.","family":"Hom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana L.","family":"Tudorascu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"McLachlan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Zammit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davneet","family":"Minhas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiquan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Laymon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph H.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Lott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beau M.","family":"Ances","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Diana","family":"Rosas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahid H.","family":"Zaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Head","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Mapstone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley T.","family":"Christian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigan L.","family":"Hartley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Alzheimer Biomarker Consortium - Down syndrome","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"issue":"5","key":"9604_CR1","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.jalz.2015.07.490","volume":"12","author":"T Annus","year":"2016","unstructured":"Annus T, Wilson LR, Hong YT, Acosta-Cabronero J, Fryer TD, Cardenas-Blanco A, Smith R, Boros I, Coles JP, Aigbirhio FI, Menon DK, Zaman SH, Nestor PJ, Holland AJ. The pattern of amyloid accumulation in the brains of adults with Down syndrome. Alzheimers Dement. 2016;12(5):538\u201345. https:\/\/doi.org\/10.1016\/j.jalz.2015.07.490.","journal-title":"Alzheimers Dement"},{"issue":"4","key":"9604_CR2","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.jalz.2015.05.013","volume":"12","author":"PJ Lao","year":"2016","unstructured":"Lao PJ, Betthauser TJ, Hillmer AT, Price JC, Klunk WE, Mihaila I, Higgins AT, Bulova PD, Hartley SL, Hardison R, Tumuluru RV, Murali D, Mathis CA, Cohen AD, Barnhart TE, Devenny DA, Mailick MR, Johnson SC, Handen BL, Christian BT. The effects of normal aging on amyloid-\u03b2 deposition in nondemented adults with Down syndrome as imaged by carbon 11-labeled Pittsburgh compound B. Alzheimers Dement. 2016;12(4):380\u201390. https:\/\/doi.org\/10.1016\/j.jalz.2015.05.013.","journal-title":"Alzheimers Dement"},{"issue":"3","key":"9604_CR3","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41582-018-0132-6","volume":"15","author":"IT Lott","year":"2019","unstructured":"Lott IT, Head E. Dementia in Down syndrome: unique insights for Alzheimer disease research. Nat Rev Neurol. 2019;15(3):135\u201347. https:\/\/doi.org\/10.1038\/s41582-018-0132-6.","journal-title":"Nat Rev Neurol"},{"issue":"11","key":"9604_CR4","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1016\/s1474-4422(21)00245-3","volume":"20","author":"J Fortea","year":"2021","unstructured":"Fortea J, Zaman SH, Hartley S, Rafii MS, Head E, Carmona-Iragui M. Alzheimer\u2019s disease associated with Down syndrome: a genetic form of dementia. Lancet Neurol. 2021;20(11):930\u201342. https:\/\/doi.org\/10.1016\/s1474-4422(21)00245-3.","journal-title":"Lancet Neurol"},{"issue":"1","key":"9604_CR5","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1006\/nbdi.1996.0003","volume":"3","author":"CA Lemere","year":"1996","unstructured":"Lemere CA, Blusztajn JK, Yamaguchi H, Wisniewski T, Saido TC, Selkoe D. Sequence of deposition of heterogeneous amyloid \u03b2-peptides and APOE in Down syndrome: Implications for initial events in amyloid plaque formation. Neurobiol Dis. 1996;3(1):16\u201332. https:\/\/doi.org\/10.1006\/nbdi.1996.0003.","journal-title":"Neurobiol Dis"},{"issue":"17","key":"9604_CR6","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.nicl.2017.10.022","volume":"1","author":"N Neale","year":"2018","unstructured":"Neale N, Padilla C, Fonseca LM, Holland T, Zaman S. Neuroimaging and other modalities to assess Alzheimer\u2019s disease in Down syndrome. Neuroimage Clin. 2018;1(17):263\u201371. https:\/\/doi.org\/10.1016\/j.nicl.2017.10.022.","journal-title":"Neuroimage Clin"},{"issue":"19","key":"9604_CR7","doi-asserted-by":"publisher","first-page":"4582","DOI":"10.3390\/jcm10194582","volume":"10","author":"T Rujeedawa","year":"2021","unstructured":"Rujeedawa T, Carrillo F\u00e9lez E, Clare IC, Fortea J, Strydom A, Rebillat AS, Coppus A, Levin J, Zaman SH. The clinical and neuropathological features of sporadic (Late-onset) and genetic forms of alzheimer\u2019s disease. J Clin Med. 2021;10(19):4582. https:\/\/doi.org\/10.3390\/jcm10194582.","journal-title":"J Clin Med"},{"issue":"4","key":"9604_CR8","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack Jr","year":"2018","unstructured":"Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E. NIA-AA research framework: toward a biological definition of Alzheimer\u2019s disease. Alzheimers Dement. 2018;14(4):535\u201362. https:\/\/doi.org\/10.1016\/j.jalz.2018.02.018.","journal-title":"Alzheimers Dement"},{"issue":"1","key":"9604_CR9","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1002\/alz.13444","volume":"20","author":"MD Zammit","year":"2024","unstructured":"Zammit MD, Betthauser TJ, McVea AK, Laymon CM, Tudorascu DL, Johnson SC, Hartley SL, Converse AK, Minhas DS, Zaman SH, Ances BM. Characterizing the emergence of amyloid and tau burden in Down syndrome. Alzheimers Dement. 2024;20(1):388\u201398. https:\/\/doi.org\/10.1002\/alz.13444.","journal-title":"Alzheimers Dement"},{"key":"9604_CR10","doi-asserted-by":"publisher","unstructured":"Iulita MF, Chavez DG, Christensen MK, Tamayo NV, Plana-Ripoll O, Rasmussen SA, Figuls MR, Alcolea D, Videla L, Barroeta I, Benejam B. Association of Alzheimer disease with life expectancy in people with Down syndrome. JAMA Netw Open. 2022;5(5):e2212910- https:\/\/doi.org\/10.1001\/jamanetworkopen.2022.12910.","DOI":"10.1001\/jamanetworkopen.2022.12910"},{"key":"9604_CR11","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13779","author":"FK Larsen","year":"2024","unstructured":"Larsen FK, Baksh RA, McGlinchey E, Langballe EM, Benejam B, Beresford-Webb J, McCarron M, Coppus A, Falquero S, Fortea J, Levin J. Age of Alzheimer\u2019s disease diagnosis in people with Down syndrome and associated factors: Results from the Horizon 21 European Down syndrome consortium. Alzheimers Dement. 2024. https:\/\/doi.org\/10.1002\/alz.13779.","journal-title":"Alzheimers Dement"},{"issue":"1","key":"9604_CR12","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12184","volume":"13","author":"AJ Aschenbrenner","year":"2021","unstructured":"Aschenbrenner AJ, Baksh RA, Benejam B, Beresford-Webb JA, Coppus A, Fortea J, Handen BL, Hartley S, Head E, Jaeger J, Levin J. Markers of early changes in cognition across cohorts of adults with Down syndrome at risk of Alzheimer\u2019s disease. Alzheimers Dement. 2021;13(1): e12184. https:\/\/doi.org\/10.1002\/dad2.12184.","journal-title":"Alzheimers Dement"},{"issue":"1","key":"9604_CR13","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12096","volume":"12","author":"SL Hartley","year":"2020","unstructured":"Hartley SL, Handen BL, Devenny D, Tudorascu D, Piro-Gambetti B, Zammit MD, Laymon CM, Klunk WE, Zaman S, Cohen A, Christian BT. Cognitive indicators of transition to preclinical and prodromal stages of Alzheimer\u2019s disease in Down syndrome. Alzheimers Dement. 2020;12(1): e12096. https:\/\/doi.org\/10.1002\/dad2.12096.","journal-title":"Alzheimers Dement"},{"issue":"3","key":"9604_CR14","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1352\/2008.46:215-228","volume":"46","author":"SJ Krinsky-McHale","year":"2008","unstructured":"Krinsky-McHale SJ, Devenny DA, Gu H, Jenkins EC, Kittler P, Murty VV, Schupf N, Scotto L, Tycko B, Urv TK, Ye L. Successful aging in a 70-year-old man with down syndrome: a case study. Intellect Dev Disabil. 2008;46(3):215\u201328. https:\/\/doi.org\/10.1352\/2008.46:215-228.","journal-title":"Intellect Dev Disabil"},{"issue":"1","key":"9604_CR15","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12256","volume":"14","author":"SL Hartley","year":"2022","unstructured":"Hartley SL, Handen BL, Tudorascu D, Lee L, Cohen A, Piro-Gambetti B, Zammit M, Klunk W, Laymon C, Zaman S, Ances BM, Sabbagh M, Christian B. Role of tau deposition in early cognitive decline in Down syndrome. Alzheimer\u2019s & Dementia: Diagnosis, Assessment & Disease Monitoring. 2022;14(1): e12256. https:\/\/doi.org\/10.1002\/dad2.12256.","journal-title":"Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring"},{"key":"9604_CR16","doi-asserted-by":"publisher","unstructured":"Hartley SL, Handen B, Tudorascu D, Lee L, Cohen A, Schworer EK, Peven JC, Zammit M, Klunk W, Laymon C, Minhas D, Luo, W, Zaman, S, Ances, B, Preboske, G, Christian, B, & the Alzheimer Biomarker Consortium. AT (N) biomarker profiles and Alzheimer's disease symptomology in Down syndrome. Alzheimer's & Dementia. 2024;20(1):366\u201375. https:\/\/doi.org\/10.1002\/alz.13446","DOI":"10.1002\/alz.13446"},{"key":"9604_CR17","doi-asserted-by":"crossref","unstructured":"Devanand DP. The interrelations between psychosis, behavioral disturbance, and depression in Alzheimer disease. Alzheimer Dis Assoc Disord. 1999;13:S3\u20138. https:\/\/journals.lww.com\/alzheimerjournal\/toc\/1999\/11002.","DOI":"10.1097\/00002093-199911001-00002"},{"issue":"1","key":"9604_CR18","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1177\/089198878800100104","volume":"1","author":"EH Rubin","year":"1988","unstructured":"Rubin EH, Drevets WC, Burke WJ. The nature of psychotic symptoms in senile dementia of the Alzheimer type. J Geriatr Psychiatry Neurol. 1988;1(1):16\u201320. https:\/\/doi.org\/10.1177\/089198878800100104.","journal-title":"J Geriatr Psychiatry Neurol"},{"issue":"190","key":"9604_CR19","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.jad.2015.09.069","volume":"15","author":"QF Zhao","year":"2016","unstructured":"Zhao QF, Tan L, Wang HF, Jiang T, Tan MS, Tan L, Xu W, Li JQ, Wang J, Lai TJ, Yu JT. The prevalence of neuropsychiatric symptoms in Alzheimer\u2019s disease: systematic review and meta-analysis. J Affect Disord. 2016;15(190):264\u201371. https:\/\/doi.org\/10.1016\/j.jad.2015.09.069.","journal-title":"J Affect Disord"},{"issue":"11","key":"9604_CR20","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1002\/gps.1013","volume":"18","author":"DJ Hart","year":"2003","unstructured":"Hart DJ, Craig D, Compton SA, Critchlow S, Kerrigan BM, McIlroy SP, Passmore AP. A retrospective study of the behavioural and psychological symptoms of mid and late phase Alzheimer\u2019s disease. Int J Geriatr Psychiatry. 2003;18(11):1037\u201342. https:\/\/doi.org\/10.1002\/gps.1013.","journal-title":"Int J Geriatr Psychiatry"},{"issue":"9","key":"9604_CR21","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1111\/j.1532-5415.1996.tb02942.x","volume":"44","author":"BC Jost","year":"1996","unstructured":"Jost BC, Grossberg GT. The evolution of psychiatric symptoms in Alzheimer\u2019s disease: a natural history study. J Am Geriatr Soc. 1996;44(9):1078\u201381. https:\/\/doi.org\/10.1111\/j.1532-5415.1996.tb02942.x.","journal-title":"J Am Geriatr Soc"},{"issue":"11\u201312","key":"9604_CR22","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1002\/(SICI)1097-0258(20000615\/30)19:11\/12<1401::AID-SIM432>3.0.CO;2-X","volume":"19","author":"RC Mohs","year":"2000","unstructured":"Mohs RC, Schmeidler J, Aryan M. Longitudinal studies of cognitive, functional and behavioural change in patients with Alzheimer\u2019s disease. Stat Med. 2000;19(11\u201312):1401\u20139. https:\/\/doi.org\/10.1002\/(SICI)1097-0258(20000615\/30)19:11\/12<1401::AID-SIM432>3.0.CO;2-X.","journal-title":"Stat Med"},{"issue":"4","key":"9604_CR23","doi-asserted-by":"publisher","first-page":"584","DOI":"10.4088\/jcp.08m04181","volume":"70","author":"FE Taragano","year":"2009","unstructured":"Taragano FE, Allegri RF, Krupitzki H, Sarasola DR, Serrano CM, Lo\u00f1 L, Lyketsos CG. Mild behavioral impairment and risk of dementia: a prospective cohort study of 358 patients. J Clin Psychiatry. 2009;70(4):584. https:\/\/doi.org\/10.4088\/jcp.08m04181.","journal-title":"J Clin Psychiatry"},{"key":"9604_CR24","doi-asserted-by":"publisher","unstructured":"Ismail Z, Smith EE, Geda Y, Sultzer D, Brodaty H, Smith G, Ag\u00fcera-Ortiz L, Sweet R, Miller D, Lyketsos CG, Area IN. Neuropsychiatric symptoms as early manifestations of emergent dementia: provisional diagnostic criteria for mild behavioral impairment. Alzheimers Dement. 2016;12(2):195\u2013202. https:\/\/doi.org\/10.1016\/j.jalz.2015.05.017.","DOI":"10.1016\/j.jalz.2015.05.017"},{"issue":"9518","key":"9604_CR25","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1016\/S0140-6736(06)68542-5","volume":"367","author":"S Gauthier","year":"2006","unstructured":"Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, Broich K, Belleville S, Brodaty H, Bennett D, Chertkow H, Cummings JL. Mild cognitive impairment. Lancet. 2006;367(9518):1262\u201370. https:\/\/doi.org\/10.1016\/S0140-6736(06)68542-5.","journal-title":"Lancet"},{"issue":"2","key":"9604_CR26","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1017\/S1041610217001880","volume":"30","author":"Z Ismail","year":"2018","unstructured":"Ismail Z, Gatchel J, Bateman DR, Barcelos-Ferreira R, Cantillon M, Jaeger J, Donovan NJ, Mortby ME. Affective and emotional dysregulation as pre-dementia risk markers: exploring the mild behavioral impairment symptoms of depression, anxiety, irritability, and euphoria. Int Psychogeriatr. 2018;30(2):185\u201396. https:\/\/doi.org\/10.1017\/S1041610217001880.","journal-title":"Int Psychogeriatr"},{"issue":"1","key":"9604_CR27","doi-asserted-by":"publisher","first-page":"171","DOI":"10.3233\/adr-210294","volume":"5","author":"MF Mendez","year":"2021","unstructured":"Mendez MF. The relationship between anxiety and Alzheimer\u2019s disease. J Alzheimers Dis Rep. 2021;5(1):171\u20137. https:\/\/doi.org\/10.3233\/adr-210294.","journal-title":"J Alzheimers Dis Rep"},{"issue":"3","key":"9604_CR28","doi-asserted-by":"publisher","first-page":"975","DOI":"10.3233\/JAD-170001","volume":"59","author":"JR Gatchel","year":"2017","unstructured":"Gatchel JR, Donovan NJ, Locascio JJ, Schultz AP, Becker JA, Chhatwal J, Papp KV, Amariglio RE, Rentz DM, Blacker D, Sperling RA. Depressive symptoms and tau accumulation in the inferior temporal lobe and entorhinal cortex in cognitively normal older adults: a pilot study. J Alzheimers Dis. 2017;59(3):975\u201385. https:\/\/doi.org\/10.3233\/JAD-170001.","journal-title":"J Alzheimers Dis"},{"issue":"1","key":"9604_CR29","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1177\/0004867414557161","volume":"49","author":"KD Harrington","year":"2015","unstructured":"Harrington KD, Lim YY, Gould E, Maruff P. Amyloid-beta and depression in healthy older adults: a systematic review. Aust N Z J Psychiatry. 2015;49(1):36\u201346. https:\/\/doi.org\/10.1177\/0004867414557161.","journal-title":"Aust N Z J Psychiatry"},{"key":"9604_CR30","doi-asserted-by":"publisher","unstructured":"Desai AK, Grossberg GT. Recognition and management of behavioral disturbances in dementia. Prim Care Companion J Clin Psychiatry. 2001;3(3):93. https:\/\/doi.org\/10.4088\/pcc.v03n0301.","DOI":"10.4088\/pcc.v03n0301"},{"key":"9604_CR31","doi-asserted-by":"publisher","unstructured":"M\u00fcller-Spahn F. Behavioral disturbances in dementia. Dialogues Clin Neurosci. 2003;5(1):49\u201359. https:\/\/doi.org\/10.31887\/dcns.2003.5.1\/fmuellerspahn.","DOI":"10.31887\/dcns.2003.5.1\/fmuellerspahn"},{"issue":"2","key":"9604_CR32","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1002\/ajmg.c.31439","volume":"169","author":"J Grieco","year":"2015","unstructured":"Grieco J, Pulsifer M, Seligsohn K, Skotko B, Schwartz A. Down syndrome: Cognitive and behavioral functioning across the lifespan. Am J Med Genet C Semin Med Genet. 2015;169(2):135\u201349. https:\/\/doi.org\/10.1002\/ajmg.c.31439.","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"9604_CR33","doi-asserted-by":"publisher","unstructured":"Channell MM, Mattie LJ, Hamilton DR, Capone GT, Mahone EM, Sherman SL, Rosser TC, Reeves RH, Kalb LG, Down Syndrome Cognition Project. Capturing cognitive and behavioral variability among individuals with Down syndrome: a latent profile analysis. J Neurodev Disord. 2021;13:1\u20134. https:\/\/doi.org\/10.1186\/s11689-021-09365-2.","DOI":"10.1186\/s11689-021-09365-2"},{"issue":"3","key":"9604_CR34","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1002\/mrdd.20159","volume":"13","author":"EM Dykens","year":"2007","unstructured":"Dykens EM. Psychiatric and behavioral disorders in persons with Down syndrome. Ment Retard Dev Disabil Res Rev. 2007;13(3):272\u20138. https:\/\/doi.org\/10.1002\/mrdd.20159.","journal-title":"Ment Retard Dev Disabil Res Rev"},{"issue":"3","key":"9604_CR35","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1080\/19315864.2018.1481473","volume":"11","author":"L Patel","year":"2018","unstructured":"Patel L, Wolter-Warmerdam K, Leifer N, Hickey F. Behavioral characteristics of individuals with Down syndrome. J Ment Health Res Intellect Disabil. 2018;11(3):221\u201346. https:\/\/doi.org\/10.1080\/19315864.2018.1481473.","journal-title":"J Ment Health Res Intellect Disabil"},{"key":"9604_CR36","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/s11065-017-9341-9","volume":"27","author":"BA Lautarescu","year":"2017","unstructured":"Lautarescu BA, Holland AJ, Zaman SH. The early presentation of dementia in people with Down syndrome: a systematic review of longitudinal studies. Neuropsychol Rev. 2017;27:31\u201345. https:\/\/doi.org\/10.1007\/s11065-017-9341-9.","journal-title":"Neuropsychol Rev"},{"issue":"4","key":"9604_CR37","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.3233\/JAD-201427","volume":"81","author":"AD Dekker","year":"2021","unstructured":"Dekker AD, Ulgiati AM, Groen H, Boxelaar VA, Sacco S, Falquero S, Carfi A, Di Paola A, Benejam B, Valldeneu S, Fopma R. The behavioral and psychological symptoms of dementia in down syndrome scale (BPSD-DS II): Optimization and further validation. J Alzheimers Dis. 2021;81(4):1505\u201327. https:\/\/doi.org\/10.3233\/JAD-201427.","journal-title":"J Alzheimers Dis"},{"key":"9604_CR38","doi-asserted-by":"publisher","unstructured":"Dekker AD, Strydom A, Coppus AM, Nizetic D, Vermeiren Y, Naud\u00e9 PJ, Van Dam D, Potier MC, Fortea J, De Deyn PP. Behavioural and psychological symptoms of dementia in Down syndrome: Early indicators of clinical Alzheimer's disease?. Cortex. 2015;73:36\u201361. https:\/\/doi.org\/10.1016\/j.cortex.2015.07.032.","DOI":"10.1016\/j.cortex.2015.07.032"},{"issue":"2","key":"9604_CR39","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1046\/j.1365-2788.2000.00263.x","volume":"44","author":"AJ Holland","year":"2000","unstructured":"Holland AJ, Hon J, Huppert FA, Stevens F. Incidence and course of dementia in people with Down\u2019s syndrome: findings from a population-based study. J Intellect Disabil Res. 2000;44(2):138\u201346. https:\/\/doi.org\/10.1046\/j.1365-2788.2000.00263.x.","journal-title":"J Intellect Disabil Res"},{"issue":"6","key":"9604_CR40","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/S1474-4422(16)00063-6","volume":"15","author":"C Ballard","year":"2016","unstructured":"Ballard C, Mobley W, Hardy J, Williams G, Corbett A. Dementia in Down\u2019s syndrome. Lancet Neurol. 2016;15(6):622\u201336. https:\/\/doi.org\/10.1016\/S1474-4422(16)00063-6.","journal-title":"Lancet Neurol"},{"issue":"2","key":"9604_CR41","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1352\/0895-8017(2008)113[73:MBRTDS]2.0.CO;2","volume":"113","author":"TK Urv","year":"2008","unstructured":"Urv TK, Zigman WB, Silverman W. Maladaptive behaviors related to dementia status in adults with Down syndrome. Am J Ment Retard. 2008;113(2):73\u201386. https:\/\/doi.org\/10.1352\/0895-8017(2008)113[73:MBRTDS]2.0.CO;2.","journal-title":"Am J Ment Retard"},{"issue":"4","key":"9604_CR42","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1046\/j.1365-2788.1998.00135.x","volume":"42","author":"SA Cooper","year":"1998","unstructured":"Cooper SA, Prasher VP. Maladaptive behaviours and symptoms of dementia in adults with Down\u2019s syndrome compared with adults with intellectual disability of other aetiologies. J Intellect Disabil Res. 1998;42(4):293\u2013300. https:\/\/doi.org\/10.1046\/j.1365-2788.1998.00135.x.","journal-title":"J Intellect Disabil Res"},{"issue":"2","key":"9604_CR43","doi-asserted-by":"publisher","first-page":"797","DOI":"10.3233\/JAD-170920","volume":"63","author":"AD Dekker","year":"2018","unstructured":"Dekker AD, Sacco S, Carfi A, Benejam B, Vermeiren Y, Beugelsdijk G, Schippers M, Hassefras L, Eleveld J, Grefelman S, Fopma R. The behavioral and psychological symptoms of dementia in down syndrome (BPSD-DS) scale: comprehensive assessment of psychopathology in down syndrome. J Alzheimers Dis. 2018;63(2):797\u2013819. https:\/\/doi.org\/10.3233\/JAD-170920.","journal-title":"J Alzheimers Dis"},{"issue":"4","key":"9604_CR44","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1111\/j.1468-3156.2005.00323.x","volume":"33","author":"A Huxley","year":"2005","unstructured":"Huxley A, Van-Schaik P, Witts P. A comparison of challenging behaviour in an adult group with Down\u2019s syndrome and dementia compared with an adult Down\u2019s syndrome group without dementia. Br J Learn Disabil. 2005;33(4):188\u201393. https:\/\/doi.org\/10.1111\/j.1468-3156.2005.00323.x.","journal-title":"Br J Learn Disabil"},{"issue":"6","key":"9604_CR45","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1111\/jar.12093","volume":"27","author":"J Carr","year":"2014","unstructured":"Carr J, Collins S. Ageing and Dementia in a Longitudinal Study of a Cohort with Down Syndrome. J Appl Res Intellect Disabil. 2014;27(6):555\u201363. https:\/\/doi.org\/10.1111\/jar.12093.","journal-title":"J Appl Res Intellect Disabil"},{"issue":"5","key":"9604_CR46","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1046\/j.1365-2788.1999.043005393.x","volume":"43","author":"MP Cosgrave","year":"1999","unstructured":"Cosgrave MP, Tyrrell J, McCarron M, Gill M, Lawlor BA. Determinants of aggression, and adaptive and maladaptive behaviour in older people with Down\u2019s syndrome with and without dementia. J Intellect Disabil Res. 1999;43(5):393\u20139. https:\/\/doi.org\/10.1046\/j.1365-2788.1999.043005393.x.","journal-title":"J Intellect Disabil Res"},{"issue":"4","key":"9604_CR47","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1017\/S0033291709990985","volume":"40","author":"F Beacher","year":"2010","unstructured":"Beacher F, Daly E, Simmons A, Prasher V, Morris R, Robinson C, Lovestone S, Murphy K, Murphy DG. Brain anatomy and ageing in non-demented adults with Down\u2019s syndrome: an in vivo MRI study. Psychol Med. 2010;40(4):611\u20139. https:\/\/doi.org\/10.1017\/S0033291709990985.","journal-title":"Psychol Med"},{"issue":"4","key":"9604_CR48","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1352\/1944-7558-115.4.265","volume":"115","author":"TK Urv","year":"2010","unstructured":"Urv TK, Zigman WB, Silverman W. Psychiatric symptoms in adults with Down syndrome and Alzheimer\u2019s disease. Am J Intellect Dev Disabil. 2010;115(4):265\u201376. https:\/\/doi.org\/10.1352\/1944-7558-115.4.265.","journal-title":"Am J Intellect Dev Disabil"},{"key":"9604_CR49","doi-asserted-by":"publisher","unstructured":"Gumus M, Multani N, Mack ML, Tartaglia MC, Alzheimer\u2019s Disease Neuroimaging Initiative. Progression of neuropsychiatric symptoms in young-onset versus late-onset Alzheimer\u2019s disease. Geroscience. 2021;43:213\u201323. https:\/\/doi.org\/10.1007\/s11357-020-00304-y.","DOI":"10.1007\/s11357-020-00304-y"},{"issue":"11","key":"9604_CR50","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.1176\/ajp.151.11.1646","volume":"151","author":"BA Lawlor","year":"1994","unstructured":"Lawlor BA, Ryan TM, Schmeidler J, Mohs RC, Davis KL. Clinical symptoms associated with age at onset in Alzheimer\u2019s disease. Am J Psychiatry. 1994;151(11):1646\u20139. https:\/\/doi.org\/10.1176\/ajp.151.11.1646.","journal-title":"Am J Psychiatry"},{"key":"9604_CR51","doi-asserted-by":"publisher","unstructured":"Handen BL, Lott IT, Christian BT, Schupf N, OBryant S, Mapstone M, Fagan AM, Lee JH, Tudorascu D, Wang MC, Head E. The Alzheimer's biomarker consortium\u2010Down Syndrome: rationale and methodology. Alzheimers Dement. 2020;12(1):e12065. https:\/\/doi.org\/10.1002\/dad2.12065.","DOI":"10.1002\/dad2.12065"},{"key":"9604_CR52","volume-title":"Stanford-Binet Intelligence Scales-Fifth Edition","author":"GH Roid","year":"2003","unstructured":"Roid GH. Stanford-Binet Intelligence Scales-Fifth Edition. Itasca, IL: Riverside Publishing; 2003."},{"key":"9604_CR53","unstructured":"Sparrow SS, Cicchetti DV, Saulnier CA. Vineland-3: Vineland adaptive behavior scales. PsychCorp; 2016."},{"key":"9604_CR54","unstructured":"Reiss S. Reiss screen for maladaptive behavior: Test manual. IDS Publishing Corporation; 1988."},{"key":"9604_CR55","unstructured":"Sturmey P, Bertman LJ. Validity of the Reiss Screen for Maladaptive Behavior. Am J Ment Retard. 1994;99(2):201\u20136. https:\/\/pubmed.ncbi.nlm.nih.gov\/7803036\/."},{"issue":"3","key":"9604_CR56","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1352\/0895-8017(1999)104<0236:catrst>2.0.co;2","volume":"104","author":"KK Walsh","year":"1999","unstructured":"Walsh KK, Shenouda N. Correlations among the Reiss Screen, the adaptive behavior scale Part II, and the aberrant behavior checklist. Am J Ment Retard. 1999;104(3):236\u201348. https:\/\/doi.org\/10.1352\/0895-8017(1999)104<0236:catrst>2.0.co;2.","journal-title":"Am J Ment Retard"},{"issue":"3","key":"9604_CR57","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.neuroimage.2006.01.021","volume":"31","author":"RS Desikan","year":"2006","unstructured":"Desikan RS, S\u00e9gonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D, Buckner RL, Dale AM, Maguire RP, Hyman BT, Albert MS. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage. 2006;31(3):968\u201380. https:\/\/doi.org\/10.1016\/j.neuroimage.2006.01.021.","journal-title":"Neuroimage"},{"issue":"1","key":"9604_CR58","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.media.2007.06.004","volume":"12","author":"BB Avants","year":"2008","unstructured":"Avants BB, Epstein CL, Grossman M, Gee JC. Symmetric diffeomorphic image registration with cross-correlation: evaluating automated labeling of elderly and neurodegenerative brain. Med Image Anal. 2008;12(1):26\u201341. https:\/\/doi.org\/10.1016\/j.media.2007.06.004.","journal-title":"Med Image Anal"},{"issue":"3","key":"9604_CR59","doi-asserted-by":"publisher","first-page":"2033","DOI":"10.1016\/j.neuroimage.2010.09.025","volume":"54","author":"BB Avants","year":"2011","unstructured":"Avants BB, Tustison NJ, Song G, Cook PA, Klein A, Gee JC. A reproducible evaluation of ANTs similarity metric performance in brain image registration. Neuroimage. 2011;54(3):2033\u201344. https:\/\/doi.org\/10.1016\/j.neuroimage.2010.09.025.","journal-title":"Neuroimage"},{"key":"9604_CR60","doi-asserted-by":"publisher","unstructured":"Braak H, Braak E. Staging of Alzheimer's disease-related neurofibrillary changes Neurobiol Aging. 1995.; 16(3):271\u201378. https:\/\/doi.org\/10.1016\/0197-4580(95)00021-6.","DOI":"10.1016\/0197-4580(95)00021-6"},{"issue":"5","key":"9604_CR61","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/j.neuron.2016.01.028","volume":"89","author":"M Sch\u00f6ll","year":"2016","unstructured":"Sch\u00f6ll M, Lockhart SN, Schonhaut DR, O\u2019Neil JP, Janabi M, Ossenkoppele R, Baker SL, Vogel JW, Faria J, Schwimmer HD, Rabinovici GD. PET imaging of tau deposition in the aging human brain. Neuron. 2016;89(5):971\u201382. https:\/\/doi.org\/10.1016\/j.neuron.2016.01.028.","journal-title":"Neuron"},{"issue":"1","key":"9604_CR62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jalz.2014.07.003","volume":"11","author":"WE Klunk","year":"2015","unstructured":"Klunk WE, Koeppe RA, Price JC, Benzinger TL, Devous MD Sr, Jagust WJ, Johnson KA, Mathis CA, Minhas D, Pontecorvo MJ, Rowe CC. The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement. 2015;11(1):1\u20135. https:\/\/doi.org\/10.1016\/j.jalz.2014.07.003.","journal-title":"Alzheimers Dement"},{"issue":"6","key":"9604_CR63","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1038\/s43587-022-00204-0","volume":"2","author":"J Therriault","year":"2022","unstructured":"Therriault J, Pascoal TA, Lussier FZ, Tissot C, Chamoun M, Bezgin G, Servaes S, Benedet AL, Ashton NJ, Karikari TK, Lantero-Rodriguez J. Biomarker modeling of Alzheimer\u2019s disease using PET-based Braak staging. Nat Aging. 2022;2(6):526\u201335. https:\/\/doi.org\/10.1038\/s43587-022-00204-0.","journal-title":"Nat Aging"},{"issue":"7","key":"9604_CR64","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1002\/gps.1545","volume":"21","author":"SL Ball","year":"2006","unstructured":"Ball SL, Holland AJ, Hon J, Huppert FA, Treppner P, Watson PC. Personality and behaviour changes mark the early stages of Alzheimer\u2019s disease in adults with Down\u2019s syndrome: findings from a prospective population-based study. Int J Geriatr Psychiatry. 2006;21(7):661\u201373. https:\/\/doi.org\/10.1002\/gps.1545.","journal-title":"Int J Geriatr Psychiatry"},{"issue":"10","key":"9604_CR65","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1111\/j.1365-2788.2006.00842.x","volume":"50","author":"AM Coppus","year":"2006","unstructured":"Coppus AM, Evenhuis H, Verberne GJ, Visser F, Van Gool P, Eikelenboom P, Van Duijin C. Dementia and mortality in persons with Down\u2019s syndrome. J Intellect Disabil Res. 2006;50(10):768\u201377. https:\/\/doi.org\/10.1111\/j.1365-2788.2006.00842.x.","journal-title":"J Intellect Disabil Res"},{"issue":"11","key":"9604_CR66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0113111","volume":"9","author":"A Ghezzo","year":"2014","unstructured":"Ghezzo A, Salvioli S, Solimando MC, Palmieri A, Chiostergi C, Scurti M, Lomartire L, Bedetti F, Cocchi G, Follo D, Pipitone E. Age-related changes of adaptive and neuropsychological features in persons with Down Syndrome. PLoS ONE. 2014;9(11): e113111. https:\/\/doi.org\/10.1371\/journal.pone.0113111.","journal-title":"PLoS ONE"},{"issue":"1","key":"9604_CR67","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1002\/gps.930100106","volume":"10","author":"VP Prasher","year":"1995","unstructured":"Prasher VP. Age-specific prevalence, thyroid dysfunction and depressive symptomatology in adults with Down syndrome and dementia. Int J Geriatr Psychiatry. 1995;10(1):25\u201331. https:\/\/doi.org\/10.1002\/gps.930100106.","journal-title":"Int J Geriatr Psychiatry"},{"key":"9604_CR68","doi-asserted-by":"publisher","unstructured":"Dekker AD, Strydom A, Coppus AM, Nizetic D, Vermeiren Y, Naud\u00e9 PJ, Van Dam D, Potier MC, Fortea J, De Deyn PP. Behavioural and psychological symptoms of dementia in Down syndrome: Early indicators of clinical Alzheimer's disease?. Cortex. 2015;73:36\u201361. https:\/\/doi.org\/10.1016\/j.cortex.2015.07.032.","DOI":"10.1016\/j.cortex.2015.07.032"},{"issue":"3","key":"9604_CR69","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1192\/bjp.165.3.399","volume":"165","author":"SA Cooper","year":"1994","unstructured":"Cooper SA, Collacott RA. Clinical features and diagnostic criteria of depression in Down\u2019s syndrome. Br J Psychiatry. 1994;165(3):399\u2013403. https:\/\/doi.org\/10.1192\/bjp.165.3.399.","journal-title":"Br J Psychiatry"},{"issue":"6","key":"9604_CR70","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1001\/archpsyc.62.6.593","volume":"62","author":"RC Kessler","year":"2005","unstructured":"Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):593\u2013602. https:\/\/doi.org\/10.1001\/archpsyc.62.6.593.","journal-title":"Arch Gen Psychiatry"}],"container-title":["Journal of Neurodevelopmental Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s11689-025-09604-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s11689-025-09604-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s11689-025-09604-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T05:43:55Z","timestamp":1744350235000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneurodevdisorders.biomedcentral.com\/articles\/10.1186\/s11689-025-09604-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,11]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["9604"],"URL":"https:\/\/doi.org\/10.1186\/s11689-025-09604-w","relation":{},"ISSN":["1866-1955"],"issn-type":[{"value":"1866-1955","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,11]]},"assertion":[{"value":"26 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This multi-site study was approved by the Internal Review Boards of the University of Pittsburgh, University of Wisconsin Madison, and University of California, Irvine.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19"}}