O4‐09‐06: Extensive amyloid pathology in remote brain regions may predict hypometabolism in functionally connected brain regions with minor amyloid pathology: An Alzheimer's disease study

Abstract

Some anatomical overlap between amyloid-aggregates (measured by [11C]PIB-PET) and local synaptic dysfunction, reflected in regional hypometabolism (measured by [18F]FDG-PET) has been shown in patients with Alzheimer's disease (AD). However, in some brain areas distinct hypometabolism despite only minor amyloid-pathology is found (hypometabolism only = HO), which cannot easily be explained by local neurotoxicity of amyloid. Aim of this multimodal imaging study was to explore if the HO-phenomenon is influenced and may be predicted by pathologies in remote but functionally connected brain regions. 19 AD-patients and 15 matched elderly healthy controls underwent an examination with [11C]PiB-PET and [18F]FDG-PET. Group comparisons between patients and controls were performed and HO was detected by subtracting of equally thresholded results-maps (SPM5, p(FDR)=0.01). In a second step, the detected HO was used as a seed-region for a functional connectivity analysis in a resting state fMRI dataset of 17 elderly healthy controls. This network of HO-connected areas (CAs) was retransferred into the brains of AD-patients to analyze pathologies in the PET-datasets in these areas. In addition, a regression analysis between the FDG-values (SUVR) in the HO and in the remaining brain-areas was calculated and the results were compared with CAs and these pathologies. A prominent HO-area was detected in the left superior frontal gyrus in the AD-patient group. In healthy controls CAs of the HO were preferably located in parietal areas, mainly left-hemispheric. Retransferred in the brains of the 19 AD-patients, these CAs were predominantly located in areas affected by amyloid-pathology and hypometabolism. This interrelation could also be highlighted by the results of the regression-analysis. The metabolism in HO shows a strong association with metabolism in left parietal areas, which are exclusively functionally connected and show a strict overlap with these pathologies.