Overview

The goals of this study are: 1) to identify biomarkers using neuroimaging that are associated with progression rate using statistical methods, and 2) to identify biomarkers that are associated with the differential diagnosis of Parkinson's disease and atypical parkinsonism.

Eligibility

Inclusion Criteria:

For Aim 1:

• Diagnosis of Parkinson disease
• Existence of sufficient clinical data from previous UTS Southwestern longitudinal study to determine progression rate (categorized as fast or slow)
• Availability of suitable matched participant in the alternate progression group (fast or slow)
• Willingness to participate in the imaging studies required for this study and to provide written informed consent

For Aim 2:

        PD subjects will be recruited in accordance with the MDS Clinical Diagnostic Criteria for
        PD.
          -  Duration of PD (since diagnosis) is < 5 years
          -  Willing to participate in imaging and clinical scoring visits, and provide written
             informed consent
          -  Subject and investigator agree that it is highly likely subject will be able to
             participate throughout the 2-year study period (no plans to move)
        MSA subjects will be recruited in accordance with the Second Consensus Statement on
        Diagnosis of Multiple System Atrophy.
          -  Duration of MSA (since diagnosis) is < 5 years
          -  Willing to participate in imaging and clinical scoring visits, and provide written
             informed consent
          -  Subject and investigator agree that it is highly likely subject will be able to
             participate throughout the 2-year study period (no plans to move away during the
             study)
        PSP subjects will be recruited in accordance with the MDS Criteria for Diagnosis of
        Progressive Supranuclear Palsy and must meet the designation of "probable PSP" for
        inclusion.
          -  Willing to participate in imaging and clinical scoring visits, and provide written
             informed consent
          -  Subject and investigator agree that it is highly likely subject will be able to
             participate throughout the 2-year study period (no plans to move away during the
             study)
        Control subjects will be recruited who meet the following criteria:
          -  Roughly age and sex matched with the subjects in the PD cohort
          -  No history or examination findings suggestive of any neurodegenerative disease
          -  Normal gait, balance, and eye movements for age
          -  No clinical evidence for symptomatic orthostatic hypotension
          -  Willing to participate in imaging and clinical scoring visits, and provide written
             informed consent
          -  Subject and investigator agree that it is highly likely subject will be able to
             participate throughout the 2-year study period (no plans to move away during the
             study)
        Exclusion Criteria:
        For Aims 1 and 2:
          -  Any contraindications to undergoing the multimodal imaging program
          -  All females of child-bearing potential, between the ages of 18-55, will be excluded
             from the study, unless they are confirmed to be not pregnant with a pregnancy test
             prior to scanning
          -  This study will require constant clear communication throughout the duration of the
             study; therefore, non-English speakers will be excluded
          -  Right-handed finger amputees
          -  Cast on right hand or fingers at the time of enrollment
          -  Has clinically significant liver, kidney, lung, metabolic or hormone disturbances
             which pose safety risk
          -  Has a current clinically significant heart disease that poses a safety risk
          -  Has a current clinically significant infectious disease or a medical comorbidity which
             poses a safety risk
          -  Has a history of relevant severe drug allergy or hypersensitivity
          -  Have a history of drug, alcohol, or substance dependence or abuse within the last
             year, or prior prolonged history of dependence or abuse
          -  Currently undergoing chemotherapy or radiation for cancer
          -  Recreational drug use in past six months
          -  Central nervous systems disease or brain injury that would preclude participation in
             this study
          -  Psychiatric or neurological disorder that would preclude participation in this study
          -  Inability to keep or maintain research appointments
        For Aim 1:
          -  Severe disease progression such that participation in the imaging tests would be
             impossible or difficult
          -  Non-availability of a suitable matched participant in the alternate progression group
             (fast or slow)
        For Aim 2:
        PD subjects
          1. Unequivocal cerebellar abnormalities
          2. Downward vertical gaze limitation or slowing of downward saccades
          3. Diagnosis of behavioral variant frontotemporal dementia or primary progressive aphasia
          4. Parkinsonian features restricted to the lower limbs for > 3 years
          5. Treatment with dopamine blockers or depleters in a time course consistent with drug
             induced parkinsonism
          6. Absence of an observable response to high dose levodopa despite moderate disease
             severity
          7. Expert considers a diagnosis of alternative syndrome more likely than PD
          8. Rapid progression of gait impairment requiring wheelchair within 5 years of onset
          9. Complete absence of progression of motor symptoms over 5 years unless due to treatment
         10. Early bulbar dysfunction within the first 5 years since diagnosis
         11. Inspiratory respiratory dysfunction (stridor or frequent sighs)
         12. Severe autonomic failure in the first 5 years
         13. Recurrent falls (>1 per year) because of impaired balance in the first 3 years
         14. Disproportionate dystonic anterocollis or hand contractures of hands or feet within 10
             years
         15. Absence of any of the common non-motor features of PD despite 5 years of disease
         16. Otherwise unexplained pyramidal tract signs (weakness, hyperreflexia, or extensor toe
             signs)
         17. Bilateral symmetric parkinsonism
        MSA subjects
          1. Clinically significant neuropathy
          2. Hallucinations not induced by drugs
          3. Onset after age 75 years
          4. Family history of ataxia or parkinsonism
          5. White matter lesions suggesting multiple sclerosis
        PSP subjects
          1. Predominant, otherwise unexplained impairment of episodic memory, suggestive of AD
             (Alzheimer's disease)
          2. Predominant, otherwise unexplained autonomic failure, e.g., orthostatic hypotension
             (orthostatic reduction in blood pressure after 3 minutes standing > 30 mm Hg systolic
             or > 15 mm Hg diastolic), suggestive of multiple system atrophy or Lewy body disease
          3. Predominant, otherwise unexplained visual hallucinations or fluctuations in alertness,
             suggestive of dementia with Lewy bodies
          4. Predominant, otherwise unexplained multisegmental upper and lower motor neuron signs,
             suggestive of motor neuron disease (pure upper motor neuron signs are not an exclusion
             criterion)
          5. Sudden onset or step-wise or rapid progression of symptoms, in conjunction with
             corresponding imaging or laboratory findings, suggestive of vascular etiology,
             autoimmune encephalitis, metabolic encephalopathies, or prion disease
          6. History of encephalitis
          7. Prominent appendicular ataxia
          8. Identifiable cause of postural instability, e.g., primary sensory deficit, vestibular
             dysfunction, severe spasticity, or lower motor neuron syndrome
        Control subjects
        a. In the investigator's opinion, an unsuitable candidate to serve as a control