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. 2024 Jun;20(6):3906-3917.
doi: 10.1002/alz.13797. Epub 2024 Apr 21.

Cortical microinfarcts in adults with Down syndrome assessed with 3T-MRI

Mateus Rozalem Aranha  1   2   3   4 , Victor Montal  1   2   5 , Hilde van den Brink  6 , Jordi Pegueroles  1   2 , Maria Carmona-Iragui  1   2   7 , Laura Videla  1   2   7 , Lucia Maure Blesa  1   2 , Bessy Benejam  1   2   7 , Javier Arranz  1 , Sílvia Valldeneu  1   2 , Isabel Barroeta  1   2 , Susana Fernández  7 , Laia Ribas  1   2 , Daniel Alcolea  1   2 , Sofía González-Ortiz  8   9 , Núria Bargalló  9   10 , Geert Jan Biessels  6 , Rafael Blesa  1   2 , Alberto Lleó  1   2 , Artur Martins Coutinho  3 , Cláudia Costa Leite  4 , Alexandre Bejanin  1   2 , Juan Fortea  1   2   7
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Cortical microinfarcts in adults with Down syndrome assessed with 3T-MRI

Mateus Rozalem Aranha et al. Alzheimers Dement. 2024 Jun.

Abstract

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.

Keywords: Alzheimer's disease; Down syndrome; cerebral amyloid angiopathy; cerebral microbleeds; cortical microinfarcts; magnetic resonance imaging; neuroimaging; small vessel diseases.

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Conflict of interest statement

DA reports receiving personal fees for advisory board services and/or speaker honoraria from Fujirebio‐Europe, Roche, Nutricia, Krka Farmacéutica, Grifols, and Esteve outside the submitted work. AL has served as a consultant or on advisory boards for Fujirebio‐Europe, Roche, Biogen, Grifols, Novartis, Eisai, Lilly, and Nutricia, outside the submitted work. JF reports serving on the advisory boards, adjudication committees, or receiving speaker honoraria from Roche, NovoNordisk, Esteve, Biogen, Laboratorios Carnot, Adamed, LMI, Novartis, Lundbeck, Roche, AC Immune, Alzheon, Zambon, Lilly, Spanish Neurological Society, T21 Research Society, Lumind foundation, Jérôme‐Lejeune Foundation, Alzheimer's Association, National Institutes of Health USA, and Instituto de Salud Carlos III. DA, AL, and JF report holding a patent for markers of synaptopathy in neurodegenerative disease (licensed to ADx, EPI8382175.0). MRA has provided paid consultancy for Veranex. MRA is a partner and director of production at Masima‐Soluções em Imagens Médicas LTDA. No other competing interests were reported. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Criteria for visual detection of cortical microinfarcts in 3T magnetic resonance imaging. FLAIR, fluid‐attenuated inversion recovery; MR, magnetic resonance
FIGURE 2
FIGURE 2
CMI prevalence along the AD clinical continuum in DS and with age in all study groups. AD, Alzheimer's disease; aDS, asymptomatic Down syndrome; CMI, cortical microinfarcts; dDS, Down syndrome‐related Alzheimer's disease dementia; DS, Down syndrome; pDS, prodromal Down syndrome‐related Alzheimer's disease; sAD, symptomatic Alzheimer's disease
FIGURE 3
FIGURE 3
Topographic distribution of cortical microinfarcts. CMI, cortical microinfarcts
See this image and copyright information in PMC

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