{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T17:28:32Z","timestamp":1793899712891,"version":"4.8.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2019-106772RB-I00"],"award-info":[{"award-number":["PID2019-106772RB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1007\/s00415-026-14165-6","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:11:10Z","timestamp":1790273470000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The link between plasma and cognitive markers for Alzheimer\u2019s disease in Down syndrome: a longitudinal study"],"prefix":"10.1007","volume":"273","author":[{"given":"Alberto","family":"Fern\u00e1ndez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa M.","family":"Molanes-L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Zuluaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Vaquero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Moldenhauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"Galv\u00e1n-Rom\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Bajo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Lagunas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3342-6572","authenticated-orcid":false,"given":"Javier","family":"Garc\u00eda-Alba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"14165_CR1","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1016\/j.jpeds.2013.06.013","volume":"163","author":"AP Presson","year":"2013","unstructured":"Presson AP, Partyka G, Jensen KM, Devine OJ, Rasmussen SA, McCabe LL et al (2013) Current estimate of Down syndrome population prevalence in the United States. J Pediatr 163:1163\u20131168. https:\/\/doi.org\/10.1016\/j.jpeds.2013.06.013","journal-title":"J Pediatr"},{"key":"14165_CR2","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1016\/s0140-6736(20)30689-9","volume":"395","author":"J Fortea","year":"2020","unstructured":"Fortea J, Vilaplana E, Carmona-Iragui M, Benejam B, Videla L, Barroeta I et al (2020) Clinical and biomarker changes of Alzheimer\u2019s disease in adults with Down syndrome: a cross-sectional study. Lancet 395:1988\u20131997. https:\/\/doi.org\/10.1016\/s0140-6736(20)30689-9","journal-title":"Lancet"},{"key":"14165_CR3","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 (2016) Dementia in Down\u2019s syndrome. Lancet Neurol 15:622\u2013636. https:\/\/doi.org\/10.1016\/s1474-4422(16)00063-6","journal-title":"Lancet Neurol"},{"key":"14165_CR4","doi-asserted-by":"publisher","DOI":"10.1186\/1866-1955-5-19","volume":"5","author":"D Mullins","year":"2013","unstructured":"Mullins D, Daly E, Simmons A, Beacher F, Foy CM, Lovestone S et al (2013) Dementia in Down\u2019s syndrome: an MRI comparison with Alzheimer\u2019s disease in the general population. J Neurodev Disord 5:19. https:\/\/doi.org\/10.1186\/1866-1955-5-19","journal-title":"J Neurodev Disord"},{"key":"14165_CR5","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1111\/jir.12074","volume":"58","author":"M McCarron","year":"2014","unstructured":"McCarron M, McCallion P, Reilly E, Mulryan N (2014) A prospective 14-year longitudinal follow-up of dementia in persons with Down syndrome. J Intellect Disabil Res 58:61\u201370. https:\/\/doi.org\/10.1111\/jir.12074","journal-title":"J Intellect Disabil Res"},{"key":"14165_CR6","doi-asserted-by":"publisher","first-page":"e2435018","DOI":"10.1001\/jamanetworkopen.2024.35018","volume":"7","author":"E Rubenstein","year":"2024","unstructured":"Rubenstein E, Tewolde S, Michals A, Weuve J, Fortea J, Fox MP et al (2024) Alzheimer dementia among individuals with Down syndrome. JAMA Netw Open 7:e2435018. https:\/\/doi.org\/10.1001\/jamanetworkopen.2024.35018","journal-title":"JAMA Netw Open"},{"key":"14165_CR7","doi-asserted-by":"publisher","first-page":"5143","DOI":"10.1002\/alz.13859","volume":"20","author":"CR Jack Jr.","year":"2024","unstructured":"Jack CR Jr., Andrews JS, Beach TG, Buracchio T, Dunn B, Graf A et al (2024) Revised criteria for diagnosis and staging of Alzheimer\u2019s disease: Alzheimer\u2019s Association Workgroup. Alzheimers Dement 20:5143\u20135169. https:\/\/doi.org\/10.1002\/alz.13859","journal-title":"Alzheimers Dement"},{"key":"14165_CR8","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/s1474-4422(22)00408-2","volume":"22","author":"AH Boerwinkle","year":"2023","unstructured":"Boerwinkle AH, Gordon BA, Wisch J, Flores S, Henson RL, Butt OH et al (2023) Comparison of amyloid burden in individuals with Down syndrome versus autosomal dominant Alzheimer\u2019s disease: a cross-sectional study. Lancet Neurol 22:55\u201365. https:\/\/doi.org\/10.1016\/s1474-4422(22)00408-2","journal-title":"Lancet Neurol"},{"key":"14165_CR9","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/s1474-4422(21)00139-3","volume":"20","author":"AM Fagan","year":"2021","unstructured":"Fagan AM, Henson RL, Li Y, Boerwinkle AH, Xiong C, Bateman RJ et al (2021) Comparison of CSF biomarkers in Down syndrome and autosomal dominant Alzheimer\u2019s disease: a cross-sectional study. Lancet Neurol 20:615\u2013626. https:\/\/doi.org\/10.1016\/s1474-4422(21)00139-3","journal-title":"Lancet Neurol"},{"key":"14165_CR10","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70135","volume":"21","author":"Y Zhou","year":"2025","unstructured":"Zhou Y, Sheehan R, Guo L, Strydom A (2025) Blood-based biomarkers for Alzheimer\u2019s disease in Down syndrome: a systematic review and meta-analysis. Alzheimers Dement 21:e70135. https:\/\/doi.org\/10.1002\/alz.70135","journal-title":"Alzheimers Dement"},{"key":"14165_CR11","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1016\/s1474-4422(18)30285-0","volume":"17","author":"J Fortea","year":"2018","unstructured":"Fortea J, Carmona-Iragui M, Benejam B, Fern\u00e1ndez S, Videla L, Barroeta I et al (2018) Plasma and CSF biomarkers for the diagnosis of Alzheimer\u2019s disease in adults with Down syndrome: a cross-sectional study. Lancet Neurol 17:860\u2013869. https:\/\/doi.org\/10.1016\/s1474-4422(18)30285-0","journal-title":"Lancet Neurol"},{"key":"14165_CR12","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-024-01513-9","volume":"16","author":"J Arranz","year":"2024","unstructured":"Arranz J, Zhu N, Rubio-Guerra S, Rodr\u00edguez-Baz \u00cd, Ferrer R, Carmona-Iragui M et al (2024) Diagnostic performance of plasma pTau(217), pTau(181), A\u03b2(1-42) and A\u03b2(1-40) in the LUMIPULSE automated platform for the detection of Alzheimer disease. Alzheimers Res Ther 16:139. https:\/\/doi.org\/10.1186\/s13195-024-01513-9","journal-title":"Alzheimers Res Ther"},{"key":"14165_CR13","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1001\/jamaneurol.2023.5319","volume":"81","author":"NJ Ashton","year":"2024","unstructured":"Ashton NJ, Brum WS, Di Molfetta G, Benedet AL, Arslan B, Jonaitis E et al (2024) Diagnostic accuracy of a plasma phosphorylated Tau 217 immunoassay for Alzheimer disease pathology. JAMA Neurol 81:255\u2013263. https:\/\/doi.org\/10.1001\/jamaneurol.2023.5319","journal-title":"JAMA Neurol"},{"key":"14165_CR14","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 et al (2018) NIA-AA Research Framework: toward a biological definition of Alzheimer\u2019s disease. Alzheimers Dement 14:535\u2013562. https:\/\/doi.org\/10.1016\/j.jalz.2018.02.018","journal-title":"Alzheimers Dement"},{"key":"14165_CR15","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/s1474-4422(21)00066-1","volume":"20","author":"B Dubois","year":"2021","unstructured":"Dubois B, Villain N, Frisoni GB, Rabinovici GD, Sabbagh M, Cappa S et al (2021) Clinical diagnosis of Alzheimer\u2019s disease: recommendations of the International Working Group. Lancet Neurol 20:484\u2013496. https:\/\/doi.org\/10.1016\/s1474-4422(21)00066-1","journal-title":"Lancet Neurol"},{"key":"14165_CR16","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1001\/jamaneurol.2024.3770","volume":"81","author":"B Dubois","year":"2024","unstructured":"Dubois B, Villain N, Schneider L, Fox N, Campbell N, Galasko D et al (2024) Alzheimer disease as a clinical-biological construct-an international working group recommendation. JAMA Neurol 81:1304\u20131311. https:\/\/doi.org\/10.1001\/jamaneurol.2024.3770","journal-title":"JAMA Neurol"},{"key":"14165_CR17","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/s1474-4422(21)00129-0","volume":"20","author":"M Carmona-Iragui","year":"2021","unstructured":"Carmona-Iragui M, Alcolea D, Barroeta I, Videla L, Mu\u00f1oz L, Van Pelt KL et al (2021) Diagnostic and prognostic performance and longitudinal changes in plasma neurofilament light chain concentrations in adults with Down syndrome: a cohort study. Lancet Neurol 20:605\u2013614. https:\/\/doi.org\/10.1016\/s1474-4422(21)00129-0","journal-title":"Lancet Neurol"},{"key":"14165_CR18","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.1038\/s41591-022-02074-w","volume":"28","author":"NJ Ashton","year":"2022","unstructured":"Ashton NJ, Janelidze S, Mattsson-Carlgren N, Binette AP, Strandberg O, Brum WS et al (2022) Differential roles of A\u03b242\/40, p-tau231 and p-tau217 for Alzheimer\u2019s trial selection and disease monitoring. Nat Med 28:2555\u20132562. https:\/\/doi.org\/10.1038\/s41591-022-02074-w","journal-title":"Nat Med"},{"key":"14165_CR19","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14364","volume":"21","author":"ME Petersen","year":"2025","unstructured":"Petersen ME, Flores-Aguilar L, Head E, Montoliu-Gaya L, Strydom A, Pape SE et al (2025) Blood biomarkers in Down syndrome: facilitating Alzheimer\u2019s disease detection and monitoring. Alzheimers Dement 21:e14364. https:\/\/doi.org\/10.1002\/alz.14364","journal-title":"Alzheimers Dement"},{"key":"14165_CR20","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.70084","volume":"17","author":"J Garc\u00eda-Alba","year":"2025","unstructured":"Garc\u00eda-Alba J, Molanes-L\u00f3pez EM, Zuluaga P, Bell-Fenellos C, Vaquero L, Alfayate E et al (2025) Cognitive markers for the distinction between asymptomatic and prodromal Alzheimer\u2019s disease in Down syndrome: correlations with volumetric brain changes. Alzheimers Dement Diagn Assess Dis Monit 17:e70084. https:\/\/doi.org\/10.1002\/dad2.70084","journal-title":"Alzheimers Dement Diagn Assess Dis Monit"},{"key":"14165_CR21","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.neurobiolaging.2019.07.017","volume":"84","author":"J Garcia-Alba","year":"2019","unstructured":"Garcia-Alba J, Ramirez-Torano F, Esteba-Castillo S, Bruna R, Moldenhauer F, Novell R et al (2019) Neuropsychological and neurophysiological characterization of mild cognitive impairment and Alzheimer\u2019s disease in Down syndrome. Neurobiol Aging 84:70\u201379. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2019.07.017","journal-title":"Neurobiol Aging"},{"key":"14165_CR22","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.ejim.2015.05.003","volume":"26","author":"D Real de Asua","year":"2015","unstructured":"Real de Asua D, Quero M, Moldenhauer F, Suarez C (2015) Clinical profile and main comorbidities of Spanish adults with Down syndrome. Eur J Intern Med 26:385\u2013391. https:\/\/doi.org\/10.1016\/j.ejim.2015.05.003","journal-title":"Eur J Intern Med"},{"key":"14165_CR23","doi-asserted-by":"publisher","first-page":"337","DOI":"10.33588\/rn.5708.2013259","volume":"57","author":"S Esteba-Castillo","year":"2013","unstructured":"Esteba-Castillo S, Dalmau-Bueno A, Ribas-Vidal N, Vila-Alsina M, Novell-Alsina R, Garcia-Alba J (2013) Adaptation and validation of CAMDEX-DS (Cambridge Examination for Mental Disorders of Older People with Down\u2019s Syndrome and others with intellectual disabilities) in Spanish population with intellectual disabilities. Rev Neurol 57:337\u2013346","journal-title":"Rev Neurol"},{"key":"14165_CR24","doi-asserted-by":"crossref","first-page":"433","DOI":"10.33588\/rn.6410.2016400","volume":"64","author":"S Esteba-Castillo","year":"2017","unstructured":"Esteba-Castillo S, Pena-Casanova J, Garcia-Alba J, Castellanos MA, Torrents-Rodas D, Rodriguez E et al (2017) Barcelona Test for Intellectual Disability: a new instrument for the neuropsychological assessment of adults with intellectual disability. Rev Neurol 64:433","journal-title":"Rev Neurol"},{"key":"14165_CR25","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1111\/jar.12959","volume":"35","author":"S Esteba-Castillo","year":"2022","unstructured":"Esteba-Castillo S, Garcia-Alba J, Rodr\u00edguez-Hildago E, Vaquero L, Novell R, Moldenhauer F et al (2022) Proposed diagnostic criteria for mild cognitive impairment in Down syndrome population. J Appl Res Intellect Disabil 35:495\u2013505. https:\/\/doi.org\/10.1111\/jar.12959","journal-title":"J Appl Res Intellect Disabil"},{"key":"14165_CR26","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.988540","author":"A Fern\u00e1ndez","year":"2022","unstructured":"Fern\u00e1ndez A, Ram\u00edrez-Tora\u00f1o F, Bru\u00f1a R, Zuluaga P, Esteba-Castillo S, Ab\u00e1solo D et al (2022) Brain signal complexity in adults with Down syndrome: potential application in the detection of mild cognitive impairment. Front Aging Neurosci. https:\/\/doi.org\/10.3389\/fnagi.2022.988540","journal-title":"Front Aging Neurosci"},{"key":"14165_CR27","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph20065096","author":"E Rodr\u00edguez-Hidalgo","year":"2023","unstructured":"Rodr\u00edguez-Hidalgo E, Garc\u00eda-Alba J, Novell R, Esteba-Castillo S (2023) The Global Deterioration Scale for Down Syndrome Population (GDS-DS): a rating scale to assess the progression of Alzheimer\u2019s disease. Int J Environ Res Public Health. https:\/\/doi.org\/10.3390\/ijerph20065096","journal-title":"Int J Environ Res Public Health"},{"key":"14165_CR28","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1002\/ddrr.1126","volume":"18","author":"SJ Krinsky-McHale","year":"2013","unstructured":"Krinsky-McHale SJ, Silverman W (2013) Dementia and mild cognitive impairment in adults with intellectual disability: issues of diagnosis. Dev Disabil Res Rev 18:31\u201342. https:\/\/doi.org\/10.1002\/ddrr.1126","journal-title":"Dev Disabil Res Rev"},{"key":"14165_CR29","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1002\/gps.4228","volume":"30","author":"R Sheehan","year":"2015","unstructured":"Sheehan R, Sinai A, Bass N, Blatchford P, Bohnen I, Bonell S et al (2015) Dementia diagnostic criteria in Down syndrome. Int J Geriatr Psychiatry 30:857\u2013863. https:\/\/doi.org\/10.1002\/gps.4228","journal-title":"Int J Geriatr Psychiatry"},{"key":"14165_CR30","doi-asserted-by":"publisher","first-page":"3234","DOI":"10.1093\/brain\/awaa286","volume":"143","author":"N Mattsson-Carlgren","year":"2020","unstructured":"Mattsson-Carlgren N, Janelidze S, Palmqvist S, Cullen N, Svenningsson AL, Strandberg O et al (2020) Longitudinal plasma p-tau217 is increased in early stages of Alzheimer\u2019s disease. Brain 143:3234\u20133241. https:\/\/doi.org\/10.1093\/brain\/awaa286","journal-title":"Brain"},{"key":"14165_CR31","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/s1474-4422(25)00237-6","volume":"24","author":"MS Rafii","year":"2025","unstructured":"Rafii MS, Schlachetzki Z, Barroeta I, Head E, Fortea J, Ances BM (2025) Down syndrome and Alzheimer\u2019s disease: insights into biomarkers, clinical symptoms, and pathology. Lancet Neurol 24:753\u2013762. https:\/\/doi.org\/10.1016\/s1474-4422(25)00237-6","journal-title":"Lancet Neurol"},{"key":"14165_CR32","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1111\/j.1365-2788.2006.00902.x","volume":"51","author":"ML Margallo-Lana","year":"2007","unstructured":"Margallo-Lana ML, Moore PB, Kay DW, Perry RH, Reid BE, Berney TP et al (2007) Fifteen-year follow-up of 92 hospitalized adults with Down\u2019s syndrome: incidence of cognitive decline, its relationship to age and neuropathology. J Intellect Disabil Res 51:463\u2013477. https:\/\/doi.org\/10.1111\/j.1365-2788.2006.00902.x","journal-title":"J Intellect Disabil Res"},{"key":"14165_CR33","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1001\/jama.2020.12134","volume":"324","author":"S Palmqvist","year":"2020","unstructured":"Palmqvist S, Janelidze S, Quiroz YT, Zetterberg H, Lopera F, Stomrud E et al (2020) Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders. JAMA 324:772\u2013781. https:\/\/doi.org\/10.1001\/jama.2020.12134","journal-title":"JAMA"},{"key":"14165_CR34","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1001\/jamaneurol.2020.4201","volume":"78","author":"S Janelidze","year":"2021","unstructured":"Janelidze S, Berron D, Smith R, Strandberg O, Proctor NK, Dage JL et al (2021) Associations of plasma phospho-tau217 levels with tau positron emission tomography in early Alzheimer disease. JAMA Neurol 78:149\u2013156. https:\/\/doi.org\/10.1001\/jamaneurol.2020.4201","journal-title":"JAMA Neurol"},{"key":"14165_CR35","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200861","author":"NR Barth\u00e9lemy","year":"2020","unstructured":"Barth\u00e9lemy NR, Horie K, Sato C, Bateman RJ (2020) Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer\u2019s disease. J Exp Med. https:\/\/doi.org\/10.1084\/jem.20200861","journal-title":"J Exp Med"},{"key":"14165_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14612-6","volume":"11","author":"M Khalil","year":"2020","unstructured":"Khalil M, Pirpamer L, Hofer E, Voortman MM, Barro C, Leppert D et al (2020) Serum neurofilament light levels in normal aging and their association with morphologic brain changes. Nat Commun 11:812. https:\/\/doi.org\/10.1038\/s41467-020-14612-6","journal-title":"Nat Commun"},{"key":"14165_CR37","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-021-00430-x","volume":"16","author":"H Zetterberg","year":"2021","unstructured":"Zetterberg H, Blennow K (2021) Moving fluid biomarkers for Alzheimer\u2019s disease from research tools to routine clinical diagnostics. Mol Neurodegener 16:10. https:\/\/doi.org\/10.1186\/s13024-021-00430-x","journal-title":"Mol Neurodegener"},{"key":"14165_CR38","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12050","volume":"12","author":"L Nyberg","year":"2020","unstructured":"Nyberg L, Lundquist A, Nordin Adolfsson A, Andersson M, Zetterberg H, Blennow K et al (2020) Elevated plasma neurofilament light in aging reflects brain white-matter alterations but does not predict cognitive decline or Alzheimer\u2019s disease. Alzheimers Dement (Amst) 12:e12050. https:\/\/doi.org\/10.1002\/dad2.12050","journal-title":"Alzheimers Dement (Amst)"},{"key":"14165_CR39","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70447","volume":"21","author":"L Vaqu\u00e9-Alc\u00e1zar","year":"2025","unstructured":"Vaqu\u00e9-Alc\u00e1zar L, Videla L, Benejam B, Del Hoyo Soriano L, Barroeta I, Fernandez S et al (2025) Generational effects in Down syndrome: enriched environment enhances functionality without reducing Alzheimer\u2019s disease risk. Alzheimers Dement 21:e70447. https:\/\/doi.org\/10.1002\/alz.70447","journal-title":"Alzheimers Dement"},{"key":"14165_CR40","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1212\/wnl.0000000000007747","volume":"93","author":"GN Bischof","year":"2019","unstructured":"Bischof GN, Jacobs HIL (2019) Subthreshold amyloid and its biological and clinical meaning: long way ahead. Neurology 93:72\u201379. https:\/\/doi.org\/10.1212\/wnl.0000000000007747","journal-title":"Neurology"},{"key":"14165_CR41","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1016\/s1474-4422(12)70191-6","volume":"11","author":"Y Stern","year":"2012","unstructured":"Stern Y (2012) Cognitive reserve in ageing and Alzheimer\u2019s disease. Lancet Neurol 11:1006\u20131012. https:\/\/doi.org\/10.1016\/s1474-4422(12)70191-6","journal-title":"Lancet Neurol"},{"key":"14165_CR42","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/s1474-4422(25)00158-9","volume":"24","author":"S Janelidze","year":"2025","unstructured":"Janelidze S, Collij LE, Mattsson-Carlgren N, Antill A, Laymon CM, Lott I et al (2025) Prediction of amyloid and tau brain deposition and cognitive decline in people with Down syndrome using plasma biomarkers: a longitudinal cohort study. Lancet Neurol 24:591\u2013600. https:\/\/doi.org\/10.1016\/s1474-4422(25)00158-9","journal-title":"Lancet Neurol"},{"key":"14165_CR43","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1016\/s1474-4422(24)00426-5","volume":"23","author":"EK Schworer","year":"2024","unstructured":"Schworer EK, Zammit MD, Wang J, Handen BL, Betthauser T, Laymon CM et al (2024) Timeline to symptomatic Alzheimer\u2019s disease in people with Down syndrome as assessed by amyloid-PET and tau-PET: a longitudinal cohort study. Lancet Neurol 23:1214\u20131224. https:\/\/doi.org\/10.1016\/s1474-4422(24)00426-5","journal-title":"Lancet Neurol"},{"key":"14165_CR44","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202114022","volume":"13","author":"N Mattsson-Carlgren","year":"2021","unstructured":"Mattsson-Carlgren N, Janelidze S, Bateman RJ, Smith R, Stomrud E, Serrano GE et al (2021) Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau. EMBO Mol Med 13:EMMM202114022. https:\/\/doi.org\/10.15252\/emmm.202114022","journal-title":"EMBO Mol Med"},{"key":"14165_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23746-0","volume":"12","author":"NC Cullen","year":"2021","unstructured":"Cullen NC, Leuzy A, Janelidze S, Palmqvist S, Svenningsson AL, Stomrud E et al (2021) Plasma biomarkers of Alzheimer\u2019s disease improve prediction of cognitive decline in cognitively unimpaired elderly populations. Nat Commun 12:3555. https:\/\/doi.org\/10.1038\/s41467-021-23746-0","journal-title":"Nat Commun"},{"key":"14165_CR46","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/s1474-4422(24)00084-x","volume":"23","author":"JK Wisch","year":"2024","unstructured":"Wisch JK, McKay NS, Boerwinkle AH, Kennedy J, Flores S, Handen BL et al (2024) Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer\u2019s disease: a cross-sectional study. Lancet Neurol 23:500\u2013510. https:\/\/doi.org\/10.1016\/s1474-4422(24)00084-x","journal-title":"Lancet Neurol"},{"key":"14165_CR47","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 et al (2024) Characterizing the emergence of amyloid and tau burden in Down syndrome. Alzheimers Dement 20:388\u2013398. https:\/\/doi.org\/10.1002\/alz.13444","journal-title":"Alzheimers Dement"},{"key":"14165_CR48","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.12910","volume":"5","author":"MF Iulita","year":"2022","unstructured":"Iulita MF, Garz\u00f3n Chavez D, Klitgaard Christensen M, Valle Tamayo N, Plana-Ripoll O, Rasmussen SA et al (2022) Association of Alzheimer Disease with life expectancy in people with Down syndrome. JAMA Netw Open 5:e2212910. https:\/\/doi.org\/10.1001\/jamanetworkopen.2022.12910","journal-title":"JAMA Netw Open"},{"key":"14165_CR49","doi-asserted-by":"publisher","first-page":"2556","DOI":"10.1093\/brain\/awu173","volume":"137","author":"SL Hartley","year":"2014","unstructured":"Hartley SL, Handen BL, Devenny DA, Hardison R, Mihaila I, Price JC et al (2014) Cognitive functioning in relation to brain amyloid-\u03b2 in healthy adults with Down syndrome. Brain 137:2556\u20132563. https:\/\/doi.org\/10.1093\/brain\/awu173","journal-title":"Brain"},{"key":"14165_CR50","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1111\/jar.12849","volume":"34","author":"W Silverman","year":"2021","unstructured":"Silverman W, Krinsky-McHale SJ, Lai F, Diana Rosas H, Hom C, Doran E et al (2021) Evaluation of the National Task Group-Early Detection Screen for Dementia: sensitivity to \u201cmild cognitive impairment\u201d in adults with Down syndrome. J Appl Res Intellect Disabil 34:905\u2013915. https:\/\/doi.org\/10.1111\/jar.12849","journal-title":"J Appl Res Intellect Disabil"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-026-14165-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-026-14165-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-026-14165-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T17:05:36Z","timestamp":1793898336000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-026-14165-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":50,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["14165"],"URL":"https:\/\/doi.org\/10.1007\/s00415-026-14165-6","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]},"assertion":[{"value":"13 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 March 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 September 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"None of the authors has any conflicts of interest to disclose.","order":1,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All participants provided written informed consent prior to participating in the study, and this study was conducted in accordance with guidelines established in the Declaration of Helsinki. This study was also approved by the ethics committee of the La Princesa University Hospital.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"619"}}