Clinical and biomarker changes of Alzheimer's disease in adults with Down syndrome : a cross-sectional study
| Autor: | Juan Fortea, Sylvain Lehmann, Shahid Zaman, Victor Montal, Tiina Annus, Maria Carmona-Iragui, Sandra Giménez, Jordi Clarimón, Bessy Benejam, Valle Camacho, Teresa Estellés, Susana Fernández, Olivia Belbin, Laura Videla, Anthony J. Holland, Ricardo S. Osorio, Jordi Pegueroles, Alberto Lleó, Isabel Barroeta, Sílvia Valldeneu, Rafael Blesa, Liam R. Wilson, Sofía González-Ortiz, Miren Altuna, Laia Muñoz, Daniel Alcolea, Sebastián Videla, Eduard Vilaplana, Ignacio Illán-Gala |
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| Přispěvatelé: | Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), IMIM-Hospital del Mar, Generalitat de Catalunya, University of Cambridge [UK] (CAM), New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), University of Barcelona, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Instituto de Salud Carlos III, Fundació Bancaria La Caixa, Fundació La Marató de TV3, Medical Research Council, and National Institutes of Health., Retiveau, Nolwenn, Holland, Anthony [0000-0003-4107-130X], Zaman, Shahid [0000-0003-1639-6014], Apollo - University of Cambridge Repository |
| Rok vydání: | 2020 |
| Předmět: |
Apolipoprotein E
MESH: United Kingdom positron emission tomography [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology nerve degeneration Disease 0302 clinical medicine middle aged nuclear magnetic resonance imaging education.field_of_study MESH: Middle Aged adult General Medicine Amyloidosis cohort analysis MESH: Case-Control Studies MESH: Amyloid beta-Peptides MESH: tau Proteins priority journal Marcadors bioquímics Alzheimer disease medicine.medical_specialty diagnostic imaging complication tau Proteins Article cerebrospinal fluid 03 medical and health sciences MESH: Cross-Sectional Studies Apolipoproteins E Alzheimer Disease MESH: Spain cross-sectional study Humans neurofilament protein Cognitive Dysfunction human procedures neurofilament protein L education MESH: Prevalence MESH: Humans ApoE protein human intellectual impairment Case-control study MESH: Adult case control study medicine.disease major clinical study mortality protein phosphorylation Cross-Sectional Studies amyloid beta protein Case-Control Studies Positron-Emission Tomography Down Syndrome MESH: Alzheimer Disease Biomarkers Pediatrics Down syndrome [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health 030204 cardiovascular system & hematology MESH: Magnetic Resonance Imaging MESH: Cognitive Dysfunction MESH: Fluorodeoxyglucose F18 Neurofilament Proteins cognitive defect Prevalence 030212 general & internal medicine MESH: Neurofilament Proteins apolipoprotein E amyloid beta protein[1-40] Middle Aged biological marker MESH: Apolipoproteins E Magnetic Resonance Imaging MESH: Positron-Emission Tomography unclassified drug fluorodeoxyglucose f 18 neurofilament light chain female Biomarker (medicine) medicine.symptom Cambridge Cognitive Examination for Older Adults with Down Syndrome Adult Population prevalence Asymptomatic tau protein male blood Fluorodeoxyglucose F18 medicine Dementia controlled study MESH: Amyloidosis amyloidosis Amyloid beta-Peptides business.industry amyloid beta protein[1-42] [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology MESH: Down Syndrome neurologic disease assessment Down Síndrome de threonine United Kingdom Spain [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health Alzheimer MESH: Biomarkers pathology business metabolism |
| Zdroj: | Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona The Lancet The Lancet, Elsevier, 2020, 395 (10242), pp.1988-1997. ⟨10.1016/S0140-6736(20)30689-9⟩ LANCET r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname Lancet (London, England) |
| ISSN: | 0140-6736 1474-547X |
| DOI: | 10.1016/S0140-6736(20)30689-9⟩ |
| Popis: | Background: 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. Methods: 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 ß peptides 1–42 and 1–40 and their ratio (Aß1–42/1–40), 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 18F-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. Findings: 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 Aß1–42/1–40 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. 18F-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. Interpretation: 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. Funding: Instituto de Salud Carlos III, Fundació Bancaria La Caixa, Fundació La Marató de TV3, Medical Research Council, and National Institutes of Health. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license |
| Databáze: | OpenAIRE |
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