Hypermetabolic cerebellar connectome in Alzheimer's disease
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Date
2020
Authors
Gupta, Vinay
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Abstract
Alzheimer’s disease (AD) is typically characterized by hypometabolism in medial-frontal lobes, posterior cingulum and temporal lobes which can be assessed using fluorodeoxyglucose (FDG) positron emission tomography (PET) in vivo. Hypermetabolism in cerebellum and pons have been also consistently reported, but it is often neglected. Some studies have dismissed it as an artifact of global mean normalization. We hypothesize that the hypermetabolic regions are also important in disease pathology in AD. Using 88 AD subjects and 88 age-sex matched Normal Controls (NL1) from the publicly available neuroimaging database enabled by Alzheimer’s disease Neuroimaging Initiative (ADNI; http://adni.loni.usc.edu/ ), we established FDG PET-based AD Classifier (FAC) that differentiated AD patients from normal individuals (sensitivity= 87.50%, specificity = 82.95%). To rule out that the observed hypermetabolism is an artifact induced by global signal intensity normalization, we replicated FAC using white matter (WM) as a reference region, and we confirmed the presence of hypermetabolism in cerebellum and pons. The brain metabolic network of AD and NL has been further analyzed using graph theory. The differences in Betweenness Centrality (BC, a measure of hubness of information flow) between AD vs NL network were correlated with region weights of FAC, which was driven by a few brain regions. In particular, the hypermetabolism in cerebellum was accompanied with higher BC while the hypometabolism in temporal lobe and posterior cingulum were accompanied with lower BC in AD. The brain regions with higher BC in AD network showed a progressive increase in FDG uptake (hypermetabolism) over 2 years in prodromal AD patients (n=39), whose baseline scans were acquired at least 2 years prior to the AD diagnosis. This progressive increase of FDG uptake was not observed in the control subjects who had mild cognitive impairment but did not develop AD over the next 2 years (n=39) nor in NL who were followed up for 2 years (n=39). This study suggests that hypermetabolism in the cerebellum associated with AD may play an important role in forming the AD-related metabolic network.
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Keywords
Hypermetabolism, Cerebellum, Alzheimer's disease, Graph theory, FDG-PET, Disease biomarker