Study of brain perfusion in adults with Down Syndrome along the Alzheimer's Disease continuum

Age-related decreases in cerebral blood flow (CBF) were observed in prefrontal regions in eCU, parietal structures in DS, and temporal lobes in sAD (Figure 1 A-D). Females had higher perfusion than males in eCU and sAD, but not in DS (Figure 1 E-H). In DS, CBF was reduced in temporal-parietal regions in asymptomatic individuals, extending to frontal areas in symptomatic cases, resembling sAD patterns (Figure 2). Symptomatic DS showed significantly lower CBF in lateral parietal regions than asymptomatic DS. Temporoparietal CBF correlated negatively with CSF-pTau-181 and positively with CSF-Aβ1-42/Aβ1-40 ratio and hippocampal volume, with the strongest association seen with hippocampal volume (Figure 3) CONCLUSION: Brain perfusion is significantly altered in adults with DS along the AD continuum, with changes detectable even before clinical symptoms. Hypoperfusion primarily affects temporoparietal and frontal regions at the symptomatic stage, closely resembling patterns seen in sAD. Notably, perfusion in the parietal areas differentiates asymptomatic from symptomatic DS and correlates strongly with key AD biomarkers. These findings highlight the potential of pCASL to detect early functional changes in this high-risk population.