Associations of Visceral Adipose Tissue Metabolism with DMN-centered Cross-Network Metabolic Expression Concordance and Cognitive Impairment in Alzheimer's Disease.

Visceral adipose tissue (VAT) has been identified as a risk factor for Alzheimer’s disease (AD). This study aimed to investigate the associations between glucose metabolism in VAT and subcutaneous adipose tissue (SAT) with abnormalities in large-scale brain metabolic networks and cognitive impairment in patients with AD. Ninety-eight patients with AD and 51 normal controls (NCs) underwent total-body 18F-FDG PET/CT examination. Glucose metabolic activity in VAT and SAT was quantified using lean body mass-corrected standardized uptake values (SULs). Independent component analysis (ICA) was applied to brain PET images to identify large-scale metabolic networks, from which subject-specific metabolic load scores were derived. A default mode network (DMN)-centered metabolic expression concordance (DMN-MEC) index was further derived to characterize individual-level relative metabolic expression patterns between the DMN and other large-scale brain networks. Group differences in adipose tissue metabolism and brain metabolic network metrics were examined. Within the AD group, correlations among abdominal adipose tissue metabolism, DMN-MEC index, and cognitive performance were assessed. Compared with NCs, patients with AD showed significantly increased glucose metabolism in both VAT and SAT, accompanied by reduced metabolic load scores in the DMN, dorsal attention network (DAN), frontoparietal network (FPN), and sensorimotor network (SMN), and lower global DMN-MEC. Correlation analyses within the AD group showed that the DMN metabolic load score was significantly positively correlated with the metabolic load scores of multiple other networks. Furthermore, VAT metabolism was significantly negatively associated with the global DMN-MEC index, whereas SAT metabolism showed no such association. VAT metabolic activity was also negatively correlated with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. In contrast, DMN metabolic load and global DMN-MEC index showed positive associations with cognitive performance. These findings revealed concomitant abdominal adipose tissue metabolic dysfunction and disruption of large-scale brain metabolic network expression in AD. Importantly, higher VAT metabolism was associated with lower global DMN-MEC and poorer cognitive performance.