Relationship of Dopamine to Cognitive Function in Parkinson's Disease
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Study type: Observational

Summary: 
      This study will examine how the brain chemical dopamine affects memory, reasoning, and other
      thought processes in people with Parkinson's disease with and without dementia and in healthy
      control subjects.

      Healthy normal volunteers and people with Parkinson's disease who are between 40 and 85 years
      of age may be eligible for this study. Pregnant women with Parkinson's disease and
      breastfeeding normal volunteers are excluded. Candidates are screened with a physical and
      neurological examination, blood tests, a brief mental test called the Mini Mental Status
      Examination, and other tests designed to assess memory, learning, reasoning, and other
      thought processes. Patients with Parkinson's disease also undergo a more thorough mental
      evaluation called the Mattis Dementia Rating Scale. The study requires about 15 hours over 4
      or 5 outpatient visits to NIH.

      Participants undergo two positron emission tomography (PET) scans on two separate days and a
      magnetic resonance imaging (MRI) scan, as follows:

      PET Scans

      The two PET procedures are done the same way, except one uses a radioactive tracer called
      [(18)F]DOPA and one uses a tracer called [(11)C]NNC-112. A catheter (small plastic tube) is
      placed in a vein in the subject's arm for injection of the tracer. The subject lies on the
      scanner bed and a special mask is fitted to his or her head to hold it in place during the
      procedure. Just before injecting the tracer, a 10-minute "transmission scan" is done of the
      head using a tracer called (68)Ge. Then, a series of scans using one of the two study tracers
      ([(18)F]DOPA or [(11)C]NNC-112 are done for about 90 minutes. About 1 hour before injection
      of the [(18)F]DOPA tracer, subjects take 200 mg of the drug carbidopa by mouth to help the
      tracer work properly. Blood pressure, breathing and heart are monitored before and after
      injection of the [(11)C]NNC-112 tracer.

      Patients with Parkinson's disease are taken off all Parkinson's medications the night before
      the [(18)F]DOPA scan and their motor function is tested the following morning before the
      scans are done, using the Unified Parkinson's Disease Rating Scale. Patients can resume all
      medications except L-DOPA (including Sinemet) after the movement test, and they can resume
      L-DOPA after the PET scan is finished.

      MRI Scan

      MRI uses a strong magnetic field and radio waves to obtain images of the brain. The subject
      lies still on a table that slides inside the scanner, a metal cylinder. They wear ear plugs
      to muffle loud knocking sounds that occur during the scanning and can communicate with the
      MRI staff at any time through an intercom.
    

Detailed description: 
      Parkinson's disease (PD) is a common neurodegenerative disorder, particularly in the elderly
      population. PD is characterized primarily by motor impairment, but cognitive impairment is
      common and dementia may occur in about 30% of patients. The pathological hallmark of PD is
      the selective degeneration of nigrostriatal dopamine neurons and the appearance of
      intracytoplasmic inclusions known as Lewy Bodies. Dopaminergic dysfunction has been widely
      demonstrated in PD patients. Reductions in [18F]FDOPA uptake has been consistently observed
      in PD, although it remains to be established whether there are relative differences between
      PD with and without dementia, and its association with cognitive function. Furthermore, data
      relating to dopamine D1 receptors in PD are limited to post mortem studies and imaging with
      the D1 tracer [11C]SCH 23390, and little is known about the role of D1 receptors in vivo and
      how it relates to clinical phenomena. The aim of the current study is to assess the
      feasibility and usefulness of imaging of the dopamine D1 receptor and dopamine terminal
      function in vivo, using PET (positron emission tomography) in patients with PD, with and
      without dementia, and to assess changes in presynaptic and postsynaptic dopaminergic markers
      in PD. The long-term goal of the present study is to further our understanding of the role of
      the dopaminergic system in the pathogenesis of PD and its relationship with cognitive and
      motor deficits of PD. Knowledge gained from the present study may assist in the development
      of novel therapeutic targets for PD.
    

Keywords: Positron Emission Tomograhy; [18F] FDOPA; [11C] NNC-112; Dopamine; Molecular Imaging; Dopamine D1 Receptor; PET; Parkinson's Disease; Cognition; Parkinson Disease; PD; Healthy Volunteer; HV