Distinct Sensitivity of MRI Versus [ ¹⁸ F]FDG‐PET To Detect Cerebral Changes Across the Alzheimer's Continuum in Down Syndrome: A Multimodal Imaging Study

Abstract Background To date, limited evidence exists on the different sensitivity of MRI versus [ 18 F]FDG‐PET to detect early cerebral changes along the Alzheimer's disease (AD) continuum in Down syndrome (DS). Therefore, we aimed to characterize volume and metabolism alterations in adults with DS and compare their performance in detecting AD clinical stages. Method Cross‐sectional study, including 92 adults with DS from the Down‐Alzheimer Barcelona Neuroimaging Initiative (34 asymptomatic without amyloid pathology [aDS A−], 20 asymptomatic with amyloid pathology [aDS A+], 12 with prodromal AD [pDS], and 26 with AD dementia [dDS]; Table 1), who underwent 3T‐MRI and [ 18 F]FDG‐PET. Amyloid status in the aDS group was determined using amyloid‐PET (>20 centiloids, n = 29) or CSF Aβ42/Aβ40 ratio (<0.062, Lumipulse, n = 25). Brain volume and metabolism values were extracted using the Hammers atlas, normalizing MRI volumes by total intracranial volume and PET images using the pons as reference region. We calculated standardized‐β coefficients, adjusted for sex and scanner, to assess the effectiveness of MRI and PET scans in identifying stages of AD (aDS A− vs. aDS A+; aDS vs. symptomatic DS [sDS=pDS + dDS]). Result Progressive brain volume loss and metabolic decline were observed along the AD continuum in DS. Compared to aDS A−, aDS A+ exhibited lower volume in multiple regions, particularly in the frontal lobe. sDS individuals showed widespread atrophy, predominantly in temporal areas (Figure 1). In contrast, no significant hypometabolism was detected in aDS A+ compared to aDS A−, but sDS individuals exhibited global hypometabolism, primarily in temporo‐parietal regions (Figure 2). Conclusion Amyloid pathology in aDS individuals is linked to frontal‐predominant atrophy without clear hypometabolism. In symptomatic stages, both MRI and [ 18 F]FDG‐PET revealed widespread involvement, with atrophy predominating in temporal regions and hypometabolism in temporo‐parietal areas. Unlike in sporadic AD, no brain region showed greater hypometabolism than atrophy, suggesting alternative contributing factors in the general population. Our findings also suggest that MRI outperforms [ 18 F]FDG‐PET in identifying brain changes associated with AD clinical stages in DS, which has implications for early diagnosis and clinical trials.