AbstractBackgroundCortical microinfarcts (CMI) are emerging biomarkers of vascular damage that are visually detectable with 3T‐MRI, associated with cognitive decline, and more frequent in AD patients. However, no study assessed CMI in Down syndrome (DS), a genetically determined form of AD. Therefore, we aimed to quantify CMI in a population‐based cohort of adults with DS and assess the relationship with age, sex, clinical status, and APOE genotype.MethodCross‐sectional, proof‐of‐principle study. We selected 31 adults with DS from the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) cohort with available 3T‐MR (8 asymptomatic, 11 prodromal AD, and 12 AD dementia individuals; target sample size: 200 DABNI subjects). An expert neuroradiologist blind to clinical diagnosis, age, and APOE status visually analyzed the 3T‐MRI images following previously validated protocol (Figure 1) to detect and manually segment CMI. First, we compared the presence and volume of CMI in the different clinical groups along the AD continuum, in APOEε4 carriers vs. non‐carriers, and in males vs. females using Chi‐square, Mann‐Whitney, or Kruskal‐Wallis tests when appropriate. Then, we assessed the association between the volume of CMI and age using Spearman's correlation test.ResultCMI were detected in 68% of adults with DS. The frequency of CMI was nominally higher in the prodromal and demented (73% and 75%, respectively) compared to the asymptomatic group (50%, p=0.46) and in males (70%) than females (64%, p=0.72), and significantly higher in APOEε4 carriers (100%) than non‐carriers (58%, p=0.05). The volume of CMI was nominally higher in prodromal and AD dementia patients (16.7 and 12.3mm3, respectively) than in asymptomatic subjects (2.6mm3, p=0.46), in males (12.3 mm3) than in females (7.9mm3, p=0.32), and in APOEε4 carriers (14.9mm3) compared to non‐carriers (7.9mm3, p=0.11) (Tables 1, 2 and 3). No correlations between age and CMI were observed (p=0.37, rSpearman= ‐0.17) (Figure 2).ConclusionCMI are detectable using 3T‐MRI in adults with DS and are more frequent than in the general population (6% in non‐demented elderly and 32% in AD dementia patients). They are more prevalent in APOEε4 carriers and might increase along the AD continuum and be more frequent in males.