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bioRxiv · 10.1101/2020.06.05.136838

18F-FDG-PET Hyperactivity in Alzheimers Disease Cerebellum and Primary Olfactory Cortex

Meadowcroft, M. D.·Purnell, C. J.·Wang, J.-L.·Karunanayaka, P.·Yang, Q.
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Abstract

Cerebellar involvement in Alzheimers disease (AD) has not been studied to the extent that cortical neuropathological changes have. Historical and recent histopathological literature demonstrate cerebellar AD pathology while functional investigation has demonstrated disrupted intrinsic cortical - cerebellar connectivity in AD. Additionally, olfactory deficits occur early in AD, prior to the onset of clinical symptoms. The neurological basis for the involvement of the cerebellum and olfactory system in the disease course remain unclear. 18F-fludeoxyglucose (FDG) positron emission tomography (PET) data from the Alzheimers Disease Neuroimaging Initiative (ADNI) were analyzed to characterize metabolism in the cerebellum and olfactory region of AD, mild-cognitive impaired (MCI), and age-matched cognitively normal (CN) controls. In contrast to known parietal and temporal lobe FDG hypo-metabolism within the default mode network in AD, a significant FDG hyper-metabolism was found in the cerebellum and olfactory cortical regions (including the piriform cortex, olfactory tubercle, anterior olfactory nucleus, and nucleus accumbens shell). The increase in cerebellum glucose utilization was shown also in late- verses early-MCI patients. The cerebellar and olfactory regions both contain inhibitory distal and inter-neuronal connections that are vulnerable to disruption in AD. The hyper-metabolism in the cerebellum and olfactory structures may reflect disruption of local and system-wide inhibitory networks due to AD neurodegeneration, suggesting a hypothetical mechanism for susceptibility of the olfactory system to early AD pathology.

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Meadowcroft, M. D., Purnell, C. J., Wang, J.-L., Karunanayaka, P., Yang, Q.. 2020-06-07. 18F-FDG-PET Hyperactivity in Alzheimers Disease Cerebellum and Primary Olfactory Cortex. https://doi.org/10.1101/2020.06.05.136838

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