This thesis has implemented three dimensional (3D) acquisition, reconstruction and analysis of dynamic ¹⁸F-dopa PET datasets. This has resulted in a marked improvement in sensitivity and reconstructed resolution leading to superior data quality compared with 2D acquired PET data and consequently, greater precision in the assessment of the functional integrity of the presynaptic dopaminergic system. In comparing 3D with 2D acquired ¹⁸F-dopa PET datasets in normal subjects, the mean putamen and caudate Ki° values in the 3D group (n=12) were 0.017 <span style='font-family:Symbol'>± 0.002 min^-1 and 0.016 <span style='font-family:Symbol'>± 0.002 min^-1, respectively, compared with the 2D group (n=8) values of 0.012 <span style='font-family:Symbol'>± 0.003 min^-1 and 0.013 <span style='font-family:Symbol'>± 0.003 min^-1.  The average coefficient of variation in the Ki° estimates of putamen and caudate values, were 12.7% and 11.7% for 3D and 24.8% and 25.0% for 2D, respectively. 3D ¹⁸F-dopa PET reproducibility, expressed as the mean Ki° difference (the mean difference in the Ki° values between the first and second scans) in the same normal subject, was 2.4% for putamen and 5.0% for caudate (n=5), compared with a previously reported 10% reproducibility for putamen data in 2D mode. Employing 3D ¹⁸F-dopa PET and contrary to all previously reported 2D PET studies, we have demonstrated bilateral putamen dopaminergic dysfunction in early hemi-PD (H&Y -1) with all individual putamen Ki° values contralateral to the clinically unaffected side falling below the normal range. This thesis has applied statistical parametric mapping (SPM) to 3D ¹⁸F-dopa PET datasets to localise focal changes in striatal and extrastriatal dopaminergic function in early and advanced PD and in progressing from early to advanced disease.  In early left hemi-PD, significant extra-striatal increases in Ki° were observed in the left anterior cingulate gyrus and dorsal midbrain region (p<0.05, corrected) along with decreases in caudate and putamen Ki°.  In advanced PD, in addition to significant putamen and caudate decreases in Ki°, extra-striatal Ki° reductions were observed in the ventral and dorsal midbrain regions (p<0.05, corrected).  No significant changes in Ki° were observed in the anterior cingulate region in advanced PD. In a direct comparison between the early and late PD groups, we observed relative Ki° reductions in ventral and dorsal midbrain, and dorsal pontine regions along with striatal Ki° reductions. Similiar results were found with an ROI approach and non-transformed data, except that the focal midbrain Ki° increase seen in early PD with SPM could not be replicated. Finally, this thesis has studied with ¹⁸F-dopa PET the relative rates of progression of early Parkinson’s disease (PD) in patients started on a dopamine agonist (ropinirole), or L-dopa therapy.

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Chapter 1 gives an overview of the relevance of studying therapy adherence in Parkinson’s disease. Chapter 2 examines drug induced neurological syndromes and considers the validity of patients’ concerns about taking prescribed medications. Chapter 3 compares different methods of assessing therapy adherence. Chapter 4 studies factors associated with sub-optimal medicine usage in 54 patients. Chapter 5 reports a study of patient perceived involvement with management decisions and an assessment of satisfaction with the movement disorder service in 107 patients. Chapter 6 explores patients’ beliefs about antiparkinson medication in 129 patients. Chapter 7 examines the effect on Parkinson’s patients of emerging data about drug side effects, specifically fibrosis due to ergot-based dopamine agonists. Chapter 8 reports on an educational intervention designed to improve Parkinson drug timing compliance. In summary, this thesis provides important new information about medicine taking in Parkinson’s disease. A fifth of PD patients take less than 80% of prescribed antiparkinson medication. Electronic monitoring is the only reliable method of accurately detecting sub-optimal medication usage. Patients who take less than 80% of prescribed medicines are more likely to be younger, have concomitant depression, be prescribed more tablets per day and have poorer quality of life. Patients are more satisfied if they are involved in management decisions and have increased intention to comply with prescribed medication if there is better communication. Poorer quality of life is associated with less intention to comply with prescribed medication. Timing of medication intake is generally irregular but can be improved by informing patients of the continuous dopaminergic theory and providing specific drug timings. Once daily drugs are taken more consistently than drugs with more frequent doses.