135 Other molecular imaging biomarker candidates to distinguish PD from other parkinsonian syndromes such as MSA include [11C]raclopride and [18F]FDG PET.136 Reduction of [11C]raclopride binding potential and [18F]FDG uptake in the putamen accurately discriminated MSA from PD.136 [18F]FDG uptake alone can be useful in the differential diagnosis of parkinsonian syndromes. The patients with PD show Inhibitors,research,lifescience,medical a significant glucose hypometabolism in the prefrontal, lateral frontal, and parietal cortices,

and the cingulate and caudate areas,137,138 whilst MSA patients exhibited decreased metabolism in the putamen, pons, and cerebellum.139 Levodopa, a dopamine precursor, has been used as the main treatment for PD since the 1960s. Along with levodopa, other enhancers of dopaminergic transmission are widely used. These include drugs that

inhibit the break-down of dopamine such as monoamine oxidase B inhibitors selegiline, rasagiline, and deprenyl; and the catechol-O-methyltransferase inhibitors entacapone and tolcapone; and dopamine receptor agonists Inhibitors,research,lifescience,medical such as bromocriptine, pramipexole, apomorphine, and ITF2357 ropinirole. Drugs that act on related systems such as amantadine and the antimuscarinic Inhibitors,research,lifescience,medical agents benztropine, trihexyphenidyl, procyclidine, and biperiden, also have a role, although primarily as adjunctive agents.140 Deep brain stimulation (DBS), an implantation of a stimulatory electrode directly into certain areas of the brain, has been successful in managing PD symptoms.141 Whilst these treatments provide symptomatic relief, transplantation of dopaminergic Inhibitors,research,lifescience,medical cell to substitute for the lost midbrain dopamine neuron could potentially reverse the pathophysiological

changes, and initial trial results have been promising.142 Molecular imaging has been used to evaluate PD treatment. For example, reductions in [11C]raclopride binding in the putamen correlate with improvements in rigidity and bradykinesia, as well as the occurrence of dyskinesia after the treatment with levodopa.143 [18F]FDG Inhibitors,research,lifescience,medical PET has also been used to assess the effect of cholinergic agents in PD with dementia, showing that donepezil treatment increases cerebral metabolism in the left angular gyrus and in the right superior and left middle orbitofrontal gyri.144 Molecular imaging may also too be used to inform the prognosis and response to treatment (so called ”theragnostics“). For example, PD patients who initially fulfilled the PD diagnostic criteria with normal dopamine transporter scans show a good prognosis and can have their antiparkinsonian therapy withdrawn without clinical deterioration.145 Such cases may be an example of nondegenerative form of parkinsonism. There are a number of difficulties when attempting to assess the progression of PD using clinical scales as these are mostly subjective, nonlinear scales and often biased toward specific symptoms.146 In addition, symptomatic therapy for PD effectively masks the symptoms for the assessment of disease progression.