Imaging Dyskinesia in People with Parkinson's Disease

Objective/Rationale:             
Levodopa-induced dyskinesias are abnormal involuntary movements that may develop with levodopa therapy for Parkinson's disease (PD). Recent studies on pre-clinical models showed that densensitization of the nicotinergic acetylcholine receptor by nicotine can modify striatal dopaminergic activity and ease dyskinesia. Of relevance, nicotine might best improve dyskinesia if striatal dopaminergic transmission is relatively intact.

Project Description:             
Recently, an imaging agent—5-[123I]Iodo-3-[2(S)-2-azetidinylmethoxy]pyridin ([¹²³I]IAP)—has been established to measure in vivo the density of nicotinergic acetylcholine receptors with single-photon emission computed tomography (SPECT) imaging. We aim to investigate nicotinergic and dopaminergic activity in PD subjects, with and without dyskinesia. These findings will be correlated with a PD-related dyskinesia brain pattern defined by positron emission tomography (PET) imaging.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:                     
The primary aim of this study is to describe dopaminergic and cholinergic interplay in the onset of dyskinesia and, consequently, to pave the way for patient-tailored therapeutic and neuroprotective treatments, possibly including nicotine.

Anticipated Outcome:          
We anticipate increased cholinergic activity in PD subjects with dyskinesia, possibly leading to increased levodopa turnover. A positive correlation between nicotinergic acetylcholine receptor density and a dyskinesia-related brain network might be also foreseen. PD patients with and without dyskinesia might show comparable dopaminergic striatal innervation loss.