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Associations of Microbleeds and Their Topography With Imaging and CSF Biomarkers of Alzheimer Pathology in Individuals With Down Syndrome.
Zsadanyi, Sara E; Morcillo-Nieto, Alejandra O; Aranha, Mateus R; Aragón, Irina; Arriola-Infante, José E; Vaqué-Alcázar, Lídia; Montal, Victor; Pegueroles, Jordi; Arranz, Javier; Rodríguez-Baz, Íñigo; Blesa, Lucia M; Videla, Laura; Barroeta, Isabel; Del Hoyo Soriano, Laura; Benejam, Bessy; Fernández, Susana; Hernandez, Aida S; Bargallo, Nuria; González-Ortiz, Sofía; Giménez, Sandra; Alcolea, Daniel; Belbin, Olivia; Lleó, Alberto; Fortea, Juan; Carmona-Iragui, Maria; Bejanin, Alexandre.
Afiliação
  • Zsadanyi SE; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Morcillo-Nieto AO; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Aranha MR; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Aragón I; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Arriola-Infante JE; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Vaqué-Alcázar L; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Montal V; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Pegueroles J; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Arranz J; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Rodríguez-Baz Í; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Blesa LM; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Videla L; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Barroeta I; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Del Hoyo Soriano L; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Benejam B; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Fernández S; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Hernandez AS; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Bargallo N; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • González-Ortiz S; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Giménez S; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Alcolea D; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Belbin O; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Lleó A; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Fortea J; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Carmona-Iragui M; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
  • Bejanin A; From the Sant Pau Memory Unit (S.E.Z., A.O.M.-N., M.R.A., I.A., J.E.A.-I., L.V.-A., V.M., J.P., J.A., Í.R.-B., L.M.B., L.V., I.B., L.H.S., B.B., A.S.H., S.G., D.A., O.B., A.L., J.F., M.C.-I., A.B.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau
Neurology ; 103(4): e209676, 2024 Aug 27.
Article em En | MEDLINE | ID: mdl-39074338
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:

This cross-sectional study included participants aged 18 years or older from the Down-Alzheimer Barcelona Neuroimaging Initiative and Sant Pau Initiative on Neurodegeneration with T1-weighted and susceptibility-weighted images. Participants underwent comprehensive assessments, including apolipoprotein E (APOE) 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:

We included 276 individuals with DS and 158 healthy euploid controls (mean age = 47.8 years, 50.92% female). Individuals with DS were more likely to have microbleeds than controls (20% vs 8.9%, p < 0.001), with more severe presentation (12% with 2+ vs 1.9%). Microbleeds increased with age (12% 20-30 years vs 60% > 60 years) and AD clinical stage (12.42% asymptomatic, 27.9% prodromal, 35.09% dementia) were more common in APOEε4 carriers (26% vs 18.3% noncarriers, p = 0.008), but not associated with vascular risk factors (p > 0.05). Microbleeds were predominantly posterior (cerebellum 33.66%; occipital 14.85%; temporal 21.29%) in participants with DS. Associations with microbleed severity were found for neuroimaging and fluid AD biomarkers, but only hippocampal volumes (standardized ß = -0.18 [-0.31, -0.06], p < 0.005) and CSF p-tau-181 concentrations (ß = 0.26 [0.12, 0.41], p < 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biomarcadores / Hemorragia Cerebral / Peptídeos beta-Amiloides / Proteínas tau / Síndrome de Down / Doença de Alzheimer Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Neurology Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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XML
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Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biomarcadores / Hemorragia Cerebral / Peptídeos beta-Amiloides / Proteínas tau / Síndrome de Down / Doença de Alzheimer Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Neurology Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos