Characterization of altered neuroenergetic patterns in Alzheimer’s Disease using combined FDG‐PET and sodium MRI

Abstract

AbstractBackground[18F]‐2‐fluoro‐2‐deoxy‐D‐glucose (FDG) positron emission tomography (PET) is applied to delineate cerebral glucose metabolic patterns in Alzheimer’s disease (AD). Sodium MR imaging (23Na‐MRI) can reveal alterations in tissue sodium concentration (TSC) in the brain, potentially reflecting mitochondrial dysfunction and impaired cellular energy state. This initial study aims at investigating disease‐specific topographical associations between glucose metabolism assessed via FDG‐PET and regional TSC from 23Na‐MRI, thus improving our understanding of neuroenergetics alteration in AD.Method20 patients with a biological biomarker‐based diagnosis of prodromal/mild AD (mean age 68±7.5; 8 females; CDR 0.75±0.57, MMSE 23.9±4.2) received an FDG‐PET, 23Na‐MRI and 1H‐MRI at 3T magnetic field (Siemens Prisma). A variable flip angle method was used to obtain TSC maps (Coste et al., 2019). To control for inter‐individual differences, FDG‐PET and TSC images were intensity‐normalized to the brainstem to create normalized glucose metabolism (nFDG) and normalized TSC maps (nTSC) (de Souza et al., 2011; Nugent et al., 2020), respectively. The Hammersmith and VolBrain Segmentation atlases were applied for region‐of‐interest analysis and to create correlation matrices between nFDG, nTSC and normalized local brain volume.ResultRegional nTSC negatively correlated with nFDG in AD patients mainly in temporal lobe structures and superior frontal gyri, indicating that decreased glucose metabolism was associated with increased TSC and vice versa. As expected, regional volume was positively correlated with nFDG in regions of the temporal lobe. When performing partial correlation controlling for volume, negative correlation clusters between nTSC and nFDG remained significant for superior frontal gyri and the anterior temporal lobes (Figure 1).ConclusionFor the first time, the association between local glucose consumption rates and sodium concentrations were investigated in AD using combined FDG‐PET and 23Na‐MRI at 3T. Consistently to our recent findings of increased TSC in AD patients (Haeger et al., 2021), the negative correlations between nTSC and nFDG values in temporal and frontal brain regions, are confirming the interplay between reduced energy metabolism and sodium increase in AD, the exact nature of which remains to be determined.