{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:00:29Z","timestamp":1790978429243,"version":"4.1.0"},"reference-count":47,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100015496","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015496","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010805","name":"Fundaci\u00f3n Tatiana P\u00e9rez de Guzm\u00e1n el Bueno","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010805","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["1RF1AG080769-01"],"award-info":[{"award-number":["1RF1AG080769-01"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG056850"],"award-info":[{"award-number":["R01 AG056850"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG061566"],"award-info":[{"award-number":["R01 AG061566"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG081394"],"award-info":[{"award-number":["R01 AG081394"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG073179"],"award-info":[{"award-number":["R01AG073179"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R21 AG056974"],"award-info":[{"award-number":["R21 AG056974"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R61AG066543"],"award-info":[{"award-number":["R61AG066543"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["H2020-SC1-BHC-2018-2020"],"award-info":[{"award-number":["H2020-SC1-BHC-2018-2020"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["INT21\/00073, PI20\/01473 and PI23\/01786"],"award-info":[{"award-number":["INT21\/00073, PI20\/01473 and PI23\/01786"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Most adults with Down syndrome will develop Alzheimer's disease (AD) due to the triplication of the amyloid precursor protein in the 21\n                      <jats:sup>st<\/jats:sup>\n                      chromosome. Predictors of condition onset are less known.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We used Medicaid and Medicare data and machine learning to identify which co-occurring conditions predict incident AD in United States adults with Down syndrome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined adults with Down syndrome enrolled in Medicaid and\/or Medicare between 2011 and 2019. We identified AD and other conditions using ICD 9 and 10 codes. We used a case-control design with risk set sampling to have that controls to mimic the distribution of times of incident AD. We trained gradient boosted trees to identify strongest predictors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The cohort had a mean age at entry of 44.6 years, 46.2% were male, and 73.7% were white non-Hispanic. 16,398 had incident AD diagnoses over the study period. The machine learning model had an area under the curve of 0.86 and high positive predictive value. Strongest predictors of increased probability of AD were age, dual Medicaid\/Medicare enrollment; incident epilepsy or incident ulcer three years before index date; any hypothyroidism, schizophrenia, or hyperlipidemia. We found synergistic interaction between epilepsy and enrollment by age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Predictors aligned with known predictors in the general population and characteristics that signal AD symptom onset. New onset epilepsy may be a relevant clinical sign. Identifying these predictors highlights areas for further etiologic inquiry and intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251385423","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T17:19:53Z","timestamp":1760721593000},"page":"1166-1176","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Novel predictors of Alzheimer's disease in Down syndrome identified using machine learning"],"prefix":"10.1177","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9146-4497","authenticated-orcid":false,"given":"Eric","family":"Rubenstein","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salina","family":"Tewolde","sequence":"additional","affiliation":[{"name":"Boston University School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Michals","sequence":"additional","affiliation":[{"name":"Boston University School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Fortea","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau- Universitat Aut\u00f2noma de Barcelona, Carrer de Sant Antoni Maria Claret, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia Pescador","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian G","family":"Skotko","sequence":"additional","affiliation":[{"name":"Down Syndrome Program, Massachusetts General Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yorghos","family":"Tripodis","sequence":"additional","affiliation":[{"name":"Boston University School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Weuve","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J","family":"Rosellini","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0143-7"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrdd.20163"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dhjo.2020.100947"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.12910"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.127"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1706537"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psc.2022.07.011"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/gps.930100106"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2004.07.008"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1017\/ipm.2016.1"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-023-00958-4"},{"key":"e_1_3_3_13_2","article-title":"The Alzheimer's biomarker consortium-Down syndrome: rationale and methodology","volume":"12","author":"Handen BL","year":"2020","unstructured":"Handen BL, Lott IT, Christian BT, et al. The Alzheimer's biomarker consortium-Down syndrome: rationale and methodology. Alzheimers Dement (Amst) 2020; 12: e12065.","journal-title":"Alzheimers Dement (Amst)"},{"key":"e_1_3_3_14_2","volume-title":"Modern Epidemiology, 3rd Edition","author":"Rothman KJ","year":"2008","unstructured":"Rothman KJ, Greenland S, Lash TL. Modern Epidemiology, 3rd Edition. Philadelphia, PA: Lippincott, Williams & Wilkins, 2008."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/1475-6773.14287"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/qje\/qjad055"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-024-01540-6"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0203246"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2019.10"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamahealthforum.2023.2320"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1352\/1944-7558-123.4.371"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00245-3"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70200"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.35018"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1214\/ss\/1032209663"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001469"},{"key":"e_1_3_3_27_2","volume-title":"CMS Chronic Conditions Data Warehouse (CCW), CCW Condition Algorithm","author":"Center for Medicare and Medicaid Services","year":"2021","unstructured":"Center for Medicare and Medicaid Services. CMS Chronic Conditions Data Warehouse (CCW), CCW Condition Algorithm. Washington, DC: Department of Health and Human Services, 2021."},{"key":"e_1_3_3_28_2","volume-title":"CMS Chronic Conditions Data Warehouse (CCW), CCW Chronic Condition Reference List","author":"Center for Medicare and Medicaid Services","year":"2021","unstructured":"Center for Medicare and Medicaid Services. CMS Chronic Conditions Data Warehouse (CCW), CCW Chronic Condition Reference List. Washington, DC: Department of Health and Human Services, 2021."},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2019.2905"},{"key":"e_1_3_3_30_2","unstructured":"Chen T He T Benesty M et al. xgboost: extreme gradient boosting. R package version 1.7.8.1. https:\/\/CRAN.R-project.org\/package=xgboost (2024). 2024."},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v028.i05"},{"key":"e_1_3_3_32_2","unstructured":"Mayer M. shapviz: SHAP visualizations. R package version 0.9.6. https:\/\/CRAN.R-project.org\/package=shapviz2024 (2024)."},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-018-0304-0"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03159-4"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2021.15"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12868"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2023.05.017"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10132776"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2012-111613"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2024.06.026"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.08.003"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2018.06.014"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11065-021-09478-4"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcad074"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-021-00597-3"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.2147\/NSS.S154723"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2017.11.014"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70151"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877251385423","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13872877251385423","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877251385423","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:09:22Z","timestamp":1777370962000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13872877251385423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,17]]},"references-count":47,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1177\/13872877251385423"],"URL":"https:\/\/doi.org\/10.1177\/13872877251385423","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,17]]}}}