Degenerative Nigrostriatal Dysfunction in Drug-induced Parkinsonism

Parkinson's disease (PD) and Drug-induced Parkinsonism (DIP) can be clinically
indistinguishable and DIP sometimes represents "unmasking of underlying PD. The objective of
this study is to determine the relationship of underlying Parkinson's disease (PD) to the
incidence and clinical outcome in DIP using non-motor assessments as a marker for
nigrostriatal degeneration.

Research Design: This is a nested case-control design to investigate risk factors associated
with the development of DIP and persistent Parkinsonism after antipsychotic (AP) withdrawal
(a potential clinical marker of underlying PD). Target enrollment is 45 subjects.

Methodology: We will examine objective olfactory function (via objective olfactory testing),
other non-motor symptoms of PD (via standardized validated questionnaires), and motor
findings (via clinical exam and quantitative gait analysis) in: 1) DIP patients (30 subjects)
compared to AP-treated patients without Parkinsonism (15 subjects) and 2) patients with
persistent Parkinsonism compared to those whose symptoms resolve in the DIP cohort followed
prospectively after a change in AP treatment. Additionally, in patients where it was
performed clinically, we will evaluate dopamine transporter SPECT imaging (DaTI) as a marker
of nigrostriatal integrity examining the ability of qualitative and semi-quantitative
analysis to distinguish between pharmacologic and degenerative Parkinsonism. We will also
measure serum uric acid and Apolipoprotein A1, two putative biomarkers in early PD, and
examine their relationship with clinical and radiologic status.