Influence of Neuroinflammation on Neuronal Function in Neurodegenerative Diseases: An 11C-(R)-PK11195 and 18F-FDG PET Study (S44.003)

Abstract

OBJECTIVE: The aims of the study are:1) To investigate the in-vivo regional relationship between microglial activation and neuronal dysfunction measured by rCMRGlc in Alzheimer's Disease (AD), mild cognitive impairment (MCI), Parkinson's disease dementia (PDD) and PD subjects without dementia and to compare this with the control subjects; 2) To investigate the relationship between microglial activation and glucose metabolism at voxel-voxel level in different neurodegenerative diseases.

BACKGROUND: AD and PD are the two most common neurodegenerative diseases characterised by a progressive neuronal dysfunction. Neurinflammation is a common feature seen in different neurodegenerative diseases, and is characterised by microglial activation. ¹¹C-®-PK11195 PET is a microglial imaging agent, while ¹⁸F-FDG PET measures the cerebral glucose metabolism.

DESIGN/METHODS: 10 AD, 10, MCI, 5 non-demented PD, 7 PDD and 16 control subjects were recruited. Subjects underwent T1 and T2 MRI, ¹¹C-®-PK11195 and ¹⁸F-FDG PET scans. Parametric images of ¹¹C-®-PK11195 binding potential (BP) and rCMRGlc were interrogated using Region of Interest (ROI), Statistical Parametric Mapping (SPM) analysis, and voxel-voxel analysis using biological parametric mapping.

RESULTS: AD, MCI, PDD, and PD subjects demonstrated significant increase in microglial activation. As group, AD, PDD, and PD subjects also demonstrated reduction in glucose metabolism compared to the healthy control group. Higher whole cortical microglial activation in AD was correlated with reduced glucose metabolism in AD and PDD. At voxel level there were significant correlation between microglial activation, cognitive scores, and reduced cerebral glucose metabolism in different cortical regions.

CONCLUSIONS: This has demonstrated significant microglial activation in AD, MCI, PDD, and PD subjects suggesting that this could be a common and an early phenomenon in neurodegenerative diseases. Significant correlation between microglial activation and rCMRGlc suggests cortical neuroinflammation could be associated with hippocampal neuronal damage and synaptic dysfunction, suggenting agents influencing microglial activation may have potential therapeutic benefit in neurodegenerative diseases.

Disclosure: Dr. Aman has nothing to disclose. Dr. Fan has nothing to disclose. Dr. Aman has nothing to disclose. Dr. Brooks has received personal compensation for activities with General Electric, Neurology, AstraZeneca Pharmaceuticals, Lundbeck, Schering-Plough Corporation, Elan Corporation, and UCB Pharma.