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Fellowhip","award":["CM23\/00291"],"award-info":[{"award-number":["CM23\/00291"]}]},{"name":"Miguel Servet grant","award":["CP20\/00038"],"award-info":[{"award-number":["CP20\/00038"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Medial temporal lobe structures are among the first areas impacted by neurofibrillary tangle pathology, making volumetric changes of these areas promising biomarkers for Alzheimer's disease. To date, little is known about the integrity of these regions in individuals with Down syndrome, a population that almost invariably develops Alzheimer's disease and thus offers a unique opportunity to determine the earliest structural changes related to the disease. We aimed to characterize the sequential involvement of medial temporal lobe structures with Alzheimer's disease progression, explore associations with fluid biomarkers of Alzheimer's pathology and assess the utility of regional volumes and cortical thickness in distinguishing Alzheimer's disease clinical stages in Down's syndrome.<\/jats:p>\n               <jats:p>One hundred and thirty-eight euploid controls and 259 adults with Down syndrome underwent clinical assessment and MRI scanning, followed by automated segmentation of the medial temporal lobe on T1-weighted images. Parametric statistical tests and local regression models were used to assess the cross-sectional association between regional volumes\/cortical thickness and Alzheimer's disease clinical stage, estimated years of onset, and CSF biomarkers. Additionally, markers were assessed in their ability to distinguish clinical stages using area under the receiver-operating characteristic curves.<\/jats:p>\n               <jats:p>Results showed a progressive loss of volume and cortical thickness in the medial temporal lobe with advancing Alzheimer's disease stage, showing reduced volume\/thickness at the dementia stage in all subregions. The asymptomatic and prodromal groups showed significant differences in the anterior and posterior hippocampus. We identified the entorhinal cortex and posterior hippocampus as the regions showing the earliest loss in Down syndrome, starting 13\u201315 years before Alzheimer's disease symptom onset. We observed non-linear structural changes with disease progression, with certain structures (e.g. the parahippocampal cortex) characterized by an initial increase in cortical thickness followed by subsequent thinning. Of all subregions, the hippocampal volumes showed the closest correlation with CSF amyloid-\u03b242\/40, tau phosphorylated at threonine 181 and neurofilament light chain levels. Further analyses demonstrated a high predictive value, similar to CSF biomarkers, of the hippocampus in differentiating between individuals with asymptomatic versus prodromal\/dementia Alzheimer's disease in Down syndrome.<\/jats:p>\n               <jats:p>This study provides a novel understanding of the progressive, non-linear volumetric changes of medial temporal lobe structures in relationship to Alzheimer's disease pathology in Down syndrome, which can have important implications for clinical trials monitoring neurodegeneration using MRI. We also show that MRI information can refine the prediction of clinical status in Down syndrome. This is particularly relevant in Down syndrome, where early clinical stages can be challenging to detect owing to neurodevelopmental intellectual disability.<\/jats:p>","DOI":"10.1093\/brain\/awaf133","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T13:57:16Z","timestamp":1744898236000},"page":"2509-2521","source":"Crossref","is-referenced-by-count":10,"title":["Medial temporal lobe atrophy in Down syndrome along the Alzheimer\u2019s disease continuum"],"prefix":"10.1093","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2241-0062","authenticated-orcid":false,"given":"Benjamin J","family":"Buehner","sequence":"first","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona , Barcelona 08041 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2202-3521","authenticated-orcid":false,"given":"Alejandra O","family":"Morcillo-Nieto","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona , Barcelona 08041 ,","place":["Spain"]},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED) , Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2033-5989","authenticated-orcid":false,"given":"Sara E","family":"Zsadanyi","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona , Barcelona 08041 ,","place":["Spain"]},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED) , Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateus","family":"Rozalem Aranha","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona , Barcelona 08041 ,","place":["Spain"]},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED) , Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3298-4601","authenticated-orcid":false,"given":"Jos\u00e9 Enrique","family":"Arriola-Infante","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona , Barcelona 08041 ,","place":["Spain"]},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED) , Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6776-6559","authenticated-orcid":false,"given":"L\u00eddia","family":"Vaqu\u00e9-Alc\u00e1zar","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona , Barcelona 08041 ,","place":["Spain"]},{"name":"Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona , Barcelona 08036 ,","place":["Spain"]},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) , Barcelona 08036 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,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5643-7971","authenticated-orcid":false,"given":"Lucia","family":"Maure Blesa","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona , Barcelona 08041 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9748-8465","authenticated-orcid":false,"given":"Laura","family":"Videla","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona , Barcelona 08041 ,","place":["Spain"]},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED) , Madrid 28029 ,","place":["Spain"]},{"name":"Barcelona Down Medical Center, Fundaci\u00f3 Catalana de S\u00edndrome de Down , Entres\u00f2l 08029, Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2764-7923","authenticated-orcid":false,"given":"Isabel","family":"Barroeta","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona , Barcelona 08041 ,","place":["Spain"]},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED) , Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4372-1599","authenticated-orcid":false,"given":"Laura","family":"Del Hoyo Soriano","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona , Barcelona 08041 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bessy","family":"Benejam","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona , Barcelona 08041 ,","place":["Spain"]},{"name":"Barcelona Down Medical Center, Fundaci\u00f3 Catalana de S\u00edndrome de Down , Entres\u00f2l 08029, Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Barcelona Down Medical Center, Fundaci\u00f3 Catalana de S\u00edndrome de Down , Entres\u00f2l 08029, Barcelona 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,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3819-3245","authenticated-orcid":false,"given":"Daniel","family":"Alcolea","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona , Barcelona 08041 ,","place":["Spain"]},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED) , Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6109-6371","authenticated-orcid":false,"given":"Olivia","family":"Belbin","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona , Barcelona 08041 ,","place":["Spain"]},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED) , Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2568-5478","authenticated-orcid":false,"given":"Alberto","family":"Lle\u00f3","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona , Barcelona 08041 ,","place":["Spain"]},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED) , Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Carmona-Iragui","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona , Barcelona 08041 ,","place":["Spain"]},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED) , Madrid 28029 ,","place":["Spain"]},{"name":"Barcelona Down Medical Center, Fundaci\u00f3 Catalana de S\u00edndrome de Down , Entres\u00f2l 08029, Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1340-638X","authenticated-orcid":false,"given":"Juan","family":"Fortea","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona , Barcelona 08041 ,","place":["Spain"]},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED) , Madrid 28029 ,","place":["Spain"]},{"name":"Barcelona Down Medical Center, Fundaci\u00f3 Catalana de S\u00edndrome de Down , Entres\u00f2l 08029, 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