Abstract Details

Title Clinical and Cognitive Correlates of Brain Inflammation in Parkinson Disease: A PET Study

Topic Movement Disorders

Presentation(s) S33 - (-)

Poster/Presentation
Number 002

Objective

Background The pathogenesis of PD is incompletely understood. Neuroinflammation in the form of microglial activation may contribute to the disease process and expression. Autopsy studies have confirmed the widespread presence of activated microglia in PD, but their significance is unclear. Foci of activated microglia can be localised in vivo using [11C]-PK11195 PET.

Design/Methods We studied 21 PD patients and 7 age-matched controls with [11C]-PK11195 PET. Between-group differences in tracer uptake were localized with voxel-based and region of interest approaches. Motor disability was assessed using the Unified Parkinson Disease Rating Scale (UPDRS) parts 2 and 3, and cognition with the Addenbrooke's Cognitive Examination (ACE-R), Montreal Cognitive Assessment (MoCA), and semantic and phonemic fluency. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS-15), and somnolence with the Epworth Sleepiness Scale (ESS).

Results The PD group overall had raised [11C]-PK11195 uptake compared to controls in the temporal lobes, brainstem and striatum. UPDRS part 2 (motor activities of daily living) correlated with putamenal, frontal and cingulate [11C]-PK11195 uptake. Motor disability (UPDRS part 3) was associated with raised [11C]-PK11195 uptake in the putamen and frontal cortex. Impaired phonemic fluency correlated with elevated right insula and prefrontal cortex [11C]-PK11195 uptake, and semantic fluency with raised left insula [11C]-PK11195 uptake. There was no association between [11C]-PK11195 binding and ACE or MoCA scores. Higher depression (GDS-15) scores were associated with diffusely raised neocortical [11C]-PK11195 uptake. Somnolence (ESS) scores correlated with elevated parieto-occipital [11C]-PK11195 uptake.

Conclusions The distribution of increased microglial activation in PD correlates with motor disability, cognitive impairment, depression and somnolence. Activated microglial imaging provides a useful biomarker of disease activity in PD and potentially a means of assessing response to putative disease modifying therapies.

Authors/Disclosures
Benjamin S. Simpson, MD (University Hospitals Leicester) PRESENTER	No disclosure on file
Francesco Sacca, MD (University Federico II)	Dr. Sacca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Sacca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lexeo. Dr. Sacca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genpharm. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medpharma. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Madison Pharma. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zai Lab. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dianthus. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Reata. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neopharm Israel. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson&Johnson. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. The institution of Dr. Sacca has received research support from AIFA. The institution of Dr. Sacca has received research support from FARA.
Nicola Pavese, MD (Newcastle University)	Dr. Pavese has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Dr. Pavese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bial. Dr. Pavese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AbbVie. Dr. Pavese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Britannia. The institution of Dr. Pavese has received research support from Multiple System Atrophy Trust. The institution of Dr. Pavese has received research support from Parkinson's UK. The institution of Dr. Pavese has received research support from Independent Research Fund Denmark. The institution of Dr. Pavese has received research support from European Union. The institution of Dr. Pavese has received research support from MRC.
Anil F. Ramlackhansingh, MD	No disclosure on file
	No disclosure on file
Roger Barker, PhD (University of Cambridge)	Roger Barker, PhD has nothing to disclose.
David J. Burn, MD (Regional Neuroscience Centre)	No disclosure on file
David J. Brooks, MD, DSc, FRCP (Imperial College London)	No disclosure on file

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