Abstract Details

Title Longitudinal Changes in Caudate Dopamine Processing in Parkinson's Disease: A Multi-Tracer PET Study

Topic Movement Disorders

Presentation(s) S33 - (-)

Poster/Presentation
Number 005

Objective

Background PD is a progressive disease with a characteristic gradient of dopaminergic dysfunction (putamen is more affected than caudate). We have recently shown that the compensatory mechanisms of dopamine processing in the putamen decline as PD progresses and might contribute to disease progression. However, the longitudinal course of the dopamine changes in the parkinsonian caudate is not known.

Design/Methods PD subjects (n=78) and healthy controls (n=35) underwent multi-tracer positron emission tomography (PET) scans using the following presynaptic dopamine markers: 1) [11C](±)dihydrotetrabenazine (DTBZ), to estimate the density of vesicular monoamine transporter type 2 (VMAT 2); 2) [11C]d-threo-methylphenidate, to label the dopamine transporter (DAT); and 3) 6-[18F]-fluoro-L-dopa, to assess striatal levodopa uptake and dopamine synthesis. Subjects were scanned at the initial visit and again after 4 and 8 years of follow-up. Non-linear multivariate regression analyses with random effects, of the form sKocc(t) or sBPND (t) = a*e(-bt-dA) +c (sKocc= standardized uptake constant; sBPND= standardized binding potential; a,b,c,d were constants; t=symptom duration; A=age at symptom onset) were utilized to model the temporal changes in the more affected caudate standardized to healthy control values.

Results The study comprised a total of 679 PET scans. We found evidence for upregulation of FD uptake when compared to DTBZ and MP binding in the more severely affected caudate throughout the disease course.

Conclusions Our data suggest that the compensatory strategy viz. upregulation of dopamine synthesis in the caudate persists throughout the PD course. Although striatal serotonergic neurons (more reduced in the parkinsonian caudate than putamen) could also process FD, the consistent upregulation of caudate FD uptake indicates that the temporal course of dopamine processing in the caudate differs from that of putamen, where this compensatory strategy breaks down in the advanced disease.

Authors/Disclosures
Nandhagopal Ramachandiran, MBBS, DM, FRCP, FAAN PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Raul De La Fuente-Fernandez, MD	No disclosure on file
A J. Stoessl, MD, FAAN (UBC)	No disclosure on file
Alessia Di Sapio	Alessia Di Sapio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche . Alessia Di Sapio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion . Alessia Di Sapio has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Merck. Alessia Di Sapio has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Alessia Di Sapio has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Sanofi . The institution of Alessia Di Sapio has received research support from Ministero della Salute. The institution of Alessia Di Sapio has received research support from Sanofi.

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