Barcelona Supercomputing Center, Aranha, Mateus Rozalem, Montal, Victor, van den Brink, Hilde, Pegueroles, Jordi, Carmona Iragui, Maria, Barcelona Supercomputing Center, Aranha, Mateus Rozalem, Montal, Victor, van den Brink, Hilde, Pegueroles, Jordi, and Carmona Iragui, Maria
BACKGROUND Cortical microinfarcts (CMI) were attributed to cerebrovascular disease and cerebral amyloid angiopathy (CAA). CAA is frequent in Down syndrome (DS) while hypertension is rare, yet no studies have assessed CMI in DS. METHODS We included 195 adults with DS, 63 with symptomatic sporadic Alzheimer's disease (AD), and 106 controls with 3T magnetic resonance imaging. We assessed CMI prevalence in each group and CMI association with age, AD clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition in DS. RESULTS CMI prevalence was 11.8\% in DS, 4.7\% in controls, and 17.5\% in sporadic AD. In DS, CMI increased in prevalence with age and the AD clinical continuum, was clustered in the parietal lobes, and was associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. DISCUSSION In DS, CMI are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic CAA phenotype. Highlights This is the first study to assess cortical microinfarcts (assessed with 3T magnetic resonance imaging) in adults with Down syndrome (DS). We studied the prevalence of cortical microinfarcts in DS and its relationship with age, the Alzheimer's disease (AD) clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition. The prevalence of cortical microinfarcts was 11.8\% in DS and increased with age and along the AD clinical continuum. Cortical microinfarcts were clustered in the parietal lobes, and were associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. In DS, cortical microinfarcts are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic phenotype of cerebral amyloid angiopathy., The authors want to acknowledge the Faculty of Medicine at the Autonomous University of Barcelona (Facultad de Medicina—Universitat Autónoma de Barcelona). The authors also thank all study participants and caregivers for their support and dedication. We also would like to thank the Fundació Catalana Síndrome de Down (https://fcsd.org/) for global support; Reyes Alcoverro, Marta Salinas, and Tania Martínez for administrative support; and Concepción Escola and Diana Garzón for nurse support. This study was funded by Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D) Program (AARFD-21-852492) to MRA. It was also supported by the Fondo de Investigaciones Sanitario, Carlos III Health Institute (co-funded by European Regional Development Fund/European Social Fund - A way to make Europe / Investing in your future) (PI20/01473 to JF, PI13/01532, PI16/01825 to RB, PI18/00335 to MCI, PI18/00435 to DA, PI14/1561, PI20/01330 to AL, PI22/00307 to AB), the CIBERNED Program 1, the National Institutes of Health (NIH) (1R01AG056850-01A1; 3RF1AG056850-01S1; AG056850, R21AG056974, and R01AG061566 to JF), the Departament de Salut de la Generalitat de Catalunya, Fundación Tatiana Pérez de Guzmán el Bueno (IIBSP-DOW-2020-151 to JF), the European Union's Horizon 2020, “MES-CoBraD” (H2020-SC1-BHC-2018-2020 / GA 965422 to JF), Brightfocus, and Life Molecular Imaging (LMI) to JF. AB acknowledges support from a Miguel Servet grant (CP20/00038) from the Carlos III Health Institute. and the Alzheimer's Association (AARG-22-923680). MCI acknowledges support from the Alzheimer's Association and Global Brain Health Institute (GBHI_ALZ-18-543740), the Jérôme Lejeune Foundation (#1913 Cycle 2019B), and the Societat Catalana de Neurologia (Premi Beca Fundació SCN 2020). VM acknowledges support from Predoctoral grants from the Carlos III Health Institute (FI18/00275). JA was supported by the Río Hortega Fellowship from Carlos III Health Institute (CM21/00243). The sponsors had n, Peer Reviewed, "Article signat per 23 autors/es: Mateus Rozalem Aranha, Victor Montal, Hilde van den Brink, Jordi Pegueroles, Maria Carmona-Iragui, Laura Videla, Lucia Maure Blesa, Bessy Benejam, Javier Arranz, Sílvia Valldeneu, Isabel Barroeta, Susana Fernández, Laia Ribas, Daniel Alcolea, Sofía González-Ortiz, Núria Bargalló, Geert Jan Biessels, Rafael Blesa, Alberto Lleó, Artur Martins Coutinho, Cláudia Costa Leite, Alexandre Bejanin, Juan Fortea", Postprint (published version)