Correspondence of Basal Forebrain Resting-State Functional Connectivity and Cerebral Glucose Metabolism Alterations With Neurotransmitter Maps in Alzheimer's Disease.

AIMS: To investigate alterations in basal forebrain (BF) subregional functional connectivity (FC), cerebral glucose metabolism, and their spatial correspondence with atlas-based neurotransmitter distributions in Alzheimer's disease (AD). METHODS: Forty-two Aβ-PET-positive AD patients and forty-one matched healthy controls (HC) underwent simultaneous PET/MRI. We analyzed resting-state FC of BF subregions (Ch1-3, Ch4) and measured cerebral glucose metabolism using 18F-FDG PET standardized uptake value ratio (SUVR). Spatial correlations with neurotransmitter maps were assessed using the JuSpace toolbox. RESULTS: Compared with HC, AD patients showed decreased FC between the left Ch4 and hippocampus/posterior cingulate gyrus, and increased FC between the right Ch4 and precentral/postcentral gyrus. Additionally, AD patients showed increased FC between the left Ch1-3 and superior temporal gyrus/insula, decreased FC between the right Ch1-3 and the orbitofrontal gyrus, and increased FC between the right Ch1-3 and the left temporal lobe (voxel-level p < 0.001, cluster-level p < 0.05, GRF correction). These FC changes were spatially correlated with serotonergic (5HT1a, 5HT4, SERT) and dopaminergic (D1, D2, DAT) receptor distributions (p < 0.05, FDR corrected). Widespread cerebral hypometabolism in temporoparietal and frontal regions was spatially correlated with serotonin, dopamine, GABA, glutamate, and kappa-opioid systems (p < 0.05, FDR corrected). CONCLUSION: The FC of BF and cerebral metabolic changes in AD show distinct spatial correspondence with specific neurotransmitter systems, highlighting the crucial involvement of serotonin and dopamine in AD pathophysiology.