Clinical and biomarker changes of Alzheimer's disease in adults with Down syndrome : a cross-sectional study
Fortea, Juan ![ORCID Identifier](/img/uab/orcid.ico)
(Center of Biomedical Investigation Network for Neurodegenerative Diseases, Madrid, Spain)
Vilaplana, Eduard ![ORCID Identifier](/img/uab/orcid.ico)
(Institut d'Investigació Biomèdica Sant Pau)
Carmona Iragui, María ![ORCID Identifier](/img/uab/orcid.ico)
(Institut d'Investigació Biomèdica Sant Pau)
Benejam, Bessy (Institut d'Investigació Biomèdica Sant Pau)
Videla Toro, Laura ![ORCID Identifier](/img/uab/orcid.ico)
(Institut d'Investigació Biomèdica Sant Pau)
Barroeta, Isabel ![ORCID Identifier](/img/uab/orcid.ico)
(Institut d'Investigació Biomèdica Sant Pau)
Fernández, Susana (Fundació Catalana Síndrome de Down)
Altuna-Azkargorta, Miren
(Institut d'Investigació Biomèdica Sant Pau)
Pegueroles, Jordi
(Institut d'Investigació Biomèdica Sant Pau)
Montal, Victor
(Institut d'Investigació Biomèdica Sant Pau)
Valldeneu, Silvia
(Institut d'Investigació Biomèdica Sant Pau)
Giménez, Sandra
(Institut d'Investigació Biomèdica Sant Pau)
González-Ortiz, Sofía
(Parc de Salut MAR de Barcelona)
Muñoz, Laia
(Institut d'Investigació Biomèdica Sant Pau)
Estellés, Teresa (Institut d'Investigació Biomèdica Sant Pau)
Illán-Gala, Ignacio
(Institut d'Investigació Biomèdica Sant Pau)
Belbin, Olivia
(Institut d'Investigació Biomèdica Sant Pau)
Camacho, Valle
(Institut d'Investigació Biomèdica Sant Pau)
Wilson, Liam Reese (Cambridge Intellectual and Developmental Disabilities Research Group, Department of Psychiatry, Douglas House, University of Cambridge, Cambridge, UK)
Annus, Tiina (Cambridge Intellectual and Developmental Disabilities Research Group, Department of Psychiatry, Douglas House, University of Cambridge, Cambridge, UK)
Osorio, Ricardo S. (Center for Sleep and Brain Health, Department of Psychiatry, New York University Langone Health, New York, NY, USA)
Videla, Sebastián
(Institut d'Investigació Biomèdica de Bellvitge)
Lehmann, Sylvain
(Institute for Regenerative Medicine & Biotherapy, Université de Montpellier, INSERM, Centre Hospitalier Universitaire de Montpellier, (LBPC-PPC), Montpellier, France)
Holland, Anthony J.. (Cambridge Intellectual and Developmental Disabilities Research Group, Department of Psychiatry, Douglas House, University of Cambridge, Cambridge, UK)
Alcolea, Daniel
(Institut d'Investigació Biomèdica Sant Pau)
Clarimón, Jordi
(Center of Biomedical Investigation Network for Neurodegenerative Diseases, Madrid, Spain)
Zaman, Shahid (Cambridge University Hospitals NHS Foundation Trust (Regne Unit))
Blesa, Rafael
(Institut d'Investigació Biomèdica Sant Pau)
Lleó, Alberto
(Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona
Date: |
2020 |
Abstract: |
Alzheimer's disease and its complications are the leading cause of death in adults with Down syndrome. Studies have assessed Alzheimer's disease in individuals with Down syndrome, but the natural history of biomarker changes in Down syndrome has not been established. We characterised the order and timing of changes in biomarkers of Alzheimer's disease in a population of adults with Down syndrome. We did a dual-centre cross-sectional study of adults with Down syndrome recruited through a population-based health plan in Barcelona (Spain) and through services for people with intellectual disabilities in Cambridge (UK). Cognitive impairment in participants with Down syndrome was classified with the Cambridge Cognitive Examination for Older Adults with Down Syndrome (CAMCOG-DS). Only participants with mild or moderate disability were included who had at least one of the following Alzheimer's disease measures: apolipoprotein E allele carrier status; plasma concentrations of amyloid β peptides 1-42 and 1-40 and their ratio (Aβ), total tau protein, and neurofilament light chain (NFL); tau phosphorylated at threonine 181 (p-tau), and NFL in cerebrospinal fluid (CSF); and one or more of PET with 18 F-fluorodeoxyglucose, PET with amyloid tracers, and MRI. Cognitively healthy euploid controls aged up to 75 years who had no biomarker abnormalities were recruited from the Sant Pau Initiative on Neurodegeneration. We used a first-order locally estimated scatterplot smoothing curve to determine the order and age at onset of the biomarker changes, and the lowest ages at the divergence with 95% CIs are also reported where appropriate. Between Feb 1, 2013, and June 28, 2019 (Barcelona), and between June 1, 2009, and Dec 31, 2014 (Cambridge), we included 388 participants with Down syndrome (257 [66%] asymptomatic, 48 [12%] with prodromal Alzheimer's disease, and 83 [21%] with Alzheimer's disease dementia) and 242 euploid controls. CSF Aβ and plasma NFL values changed in individuals with Down syndrome as early as the third decade of life, and amyloid PET uptake changed in the fourth decade. 18 F-fluorodeoxyglucose PET and CSF p-tau changes occurred later in the fourth decade of life, followed by hippocampal atrophy and changes in cognition in the fifth decade of life. Prodromal Alzheimer's disease was diagnosed at a median age of 50·2 years (IQR 47·5-54·1), and Alzheimer's disease dementia at 53·7 years (49·5-57·2). Symptomatic Alzheimer's disease prevalence increased with age in individuals with Down syndrome, reaching 90-100% in the seventh decade of life. Alzheimer's disease in individuals with Down syndrome has a long preclinical phase in which biomarkers follow a predictable order of changes over more than two decades. The similarities with sporadic and autosomal dominant Alzheimer's disease and the prevalence of Down syndrome make this population a suitable target for Alzheimer's disease preventive treatments. Instituto de Salud Carlos III, Fundació Bancaria La Caixa, Fundació La Marató de TV3, Medical Research Council, and National Institutes of Health. |
Note: |
Altres ajuts: Instituto de Salud Carlos III, Fundació Bancaria La Caixa, Fundació La Marató de TV3, Medical Research Council, and National Institutes of Health. |
Rights: |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. ![Creative Commons](/img/licenses/by-nc-nd.ico) |
Language: |
Anglès |
Document: |
Article ; recerca ; Versió publicada |
Published in: |
The Lancet (British), Vol. 395 (june 2020) , p. 1988-1997, ISSN 1474-547X |
DOI: 10.1016/S0140-6736(20)30689-9
PMID: 32593336
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Record created 2020-07-13, last modified 2023-11-30