Increased cerebral microbleeds and cortical superficial siderosis in pediatric patients with Down syndrome

Background: Patients with Down syndrome carry a third copy of the amyloid precursor protein gene, which is localized on chromosome 21. Consequently, these patients are prone to develop early-onset Alzheimer disease and cerebral amyloid angiopathy. Post-mortem studies suggest increased amyloid deposition to be already detectable in children with Down syndrome. The aim of our study was to evaluate if amyloid-related changes in pediatric Down syndrome patients can be detected in vivo using MRI biomarkers of cerebral microbleeds and cortical superficial siderosis. Materials and methods: This retrospective study included 12 patients with Down syndrome (mean age = 5.0 years) and 12 age-matched control subjects (mean age = 4.8 years). Frequency and location of microbleeds and siderosis were assessed on blood-sensitive MRI sequences in a consensus reading by two radiologists applying a modified Microbleed Anatomical Rating Scale. Results: Down syndrome patients showed a significantly higher mean microbleeds count and likelihood of siderosis than age-matched controls. Across groups, the highest microbleeds count was found in lobar regions (gray and white matter of frontal, parietal, temporal, and occipital lobes, and the insula), while fewer microbleeds were located in subcortical and infratentorial regions. The number of microbleeds increased over time in all three Down syndrome patients with a follow-up exam. Conclusion: In vivo MRI biomarkers can support the diagnosis of early-onset cerebral amyloid angiopathy, which might already be present in pediatric Down syndrome patients. This might contribute to clinical decision-making and potentially to the development of therapeutic and prophylactic approaches, as cerebral amyloid angiopathy increases the risk for intracranial hemorrhage and may be associated with increased risk of developing Alzheimer disease.