Associations of Microbleeds and Their Topography With Imaging and CSF Biomarkers of Alzheimer Pathology in Individuals With Down Syndrome
Sára E. Zsadanyi, Alejandra O. Morcillo‐Nieto, Mateus Rozalem Aranha, Irina Aragón, José Enrique Arriola‐Infante, Lídia Vaqué‐Alcázar, Víctor Montal, Jordi Pegueroles, Javier Arranz, Íñigo Rodríguez‐Baz, Lucía Maure-Blesa, Laura Videla, Isabel Barroeta, Laura del Hoyo Soriano, Bessy Benejam, Susana Fernández, Aida S. Hernandez, Núria Bargalló, Sofía González‐Ortiz, Sandra Giménez, Daniel Alcolea, Olivia Belbin, Alberto Lleó, Juan Fortea, María Carmona‐Iragui, Alexandre Bejanin
Abstract
BACKGROUND AND OBJECTIVES: Cerebral hemorrhages are an exclusion criterion and potential adverse effect of antiamyloid agents. It is, therefore, critical to characterize the natural history of cerebral microbleeds in populations genetically predisposed to Alzheimer disease (AD), such as Down syndrome (DS). We aimed to assess microbleed emergence in adults with DS across the AD spectrum, defining their topography and associations with clinical variables, cognitive outcomes, and fluid and neuroimaging biomarkers. METHODS: ) genotyping; fluid and plasma determinations of beta-amyloid, tau, and neurofilament light; cognitive outcomes (Cambridge Cognitive Examination and modified Cued Recall Test); and vascular risk factors (hypertension, diabetes mellitus, and dyslipidemia). We manually segmented microbleeds and characterized their topography. Associations between microbleed severity and AD biomarkers were explored using between-group comparisons (none vs 1 vs 2+) and multivariate linear models. RESULTS: < 0.005) survived regression controlling for age and disease stage, respectively. Microbleeds had limited effect on cognitive outcomes. DISCUSSION: In participants with DS, microbleeds present with a posterior, lobar predominance, are associated with disease severity, but do not affect cognitive performance. These results suggest an interplay between AD pathology and vascular lesions, implicating microbleeds as a risk factor limiting the use of antiamyloid agents in this population.