Development of Cognitive Assessment Tools in Parkinson Disease

General Design and Methods The overall goal of this proposal is to validate ANAM-PD as an assessment tool for cognitive status in PD. We propose a comprehensive strategy to evaluate the sensitivity and specificity of ANAM-PD in detecting cognitive changes in patients with a diagnosis of PD (n=50) and healthy controls (n=25). The specific testing domains of the ANAM-PD battery will be validated against standardized neuropsychological testing, described in detail below. The reliability of the ANAM-PD battery will be evaluated through a test-retest procedure in a subset of 50 subjects (25 PD and 25 HC). This strategy will enable us to evaluate the individual domains of the ANAM-PD computerized cognitive test and establish a battery as a standard test to efficiently measure cognitive changes in PD. We also propose to explore functional neuroimaging of the cholinergic system using \[123I\] IBVM and SPECT, a marker of vesicular acetylcholine transporter and a measure of the integrity of the cholinergic neuronal system. Identifying and validating ANAM-PD as an efficient tool for assessing cognitive changes in PD and exploring the cholinergic transporter system in PD through functional neuroimaging could predict sub-sets of PD patients 'at risk' for developing dementia and help elucidate the neurochemistry related to cognitive decline in PD

• [123I] IBVM and SPECT imaging (Drug), also known as FUNCTIONAL BRAIN IMAGING: Subjects will be injected with up to 4 mCi of 123-I IBVM followed by SPECT imaging.
• Subjects will undergo the 123-I IBVM imaging visit (Drug), also known as FUNCTIONAL BRAIN IMAGING: Subjects will be injected with a bolus of up to 4 mCi of 123-I IBVM followed by serial SPECT imaging.

Primary outcomes

• The overall goal of this proposal is to validate ANAM-PD as an assessment tool for cognitive status in PD [6 mos]

Sex: All, ages: 30 Years to any, accepts healthy volunteers

Inclusion and Exclusion Criteria

PD subjects

Inclusion criteria:

* The participant is 30 years or older.
* Written informed consent is obtained.
* Participants have a clinical diagnosis of Parkinson's disease based on Brain Bank Criteria.
* Mini-mental status examination (MMSE) score ≥24 or significant cognitive dysfunction based clinical mental status exam.
* Geriatric Depression Scales (GDS) ≤ 10.
* For females, non-child bearing potential a negative urine or serum pregnancy test on day of 123-I IBVM injection.

Exclusion criteria:

* The subject has a clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness
* The subject has any disorder that may interfere with drug absorption distribution, metabolism, or excretion (including gastrointestinal surgery).
* Pregnancy

Healthy Control Subjects

Inclusion criteria:

* The participant is 50 years or older.
* Written informed consent is obtained.
* Negative history of neurological or psychiatric illness based on evaluation by a research physician.
* Mini-Mental Status Exam score ≥28.
* For females, non-child bearing potential a negative urine or serum pregnancy test on day of 123-I IBVM injection.

Exclusion criteria:

* The subject has a clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness.
* The subject has any disorder that may interfere with drug absorption distribution, metabolism, or excretion (including gastrointestinal surgery).
* The subject has received an investigational drug within 60 days before the screening visit.

• Kabat MH, Kane RL, Jefferson AL, DiPino RK. Construct validity of selected Automated Neuropsychological Assessment Metrics (ANAM) battery measures. Clin Neuropsychol. 2001 Dec;15(4):498-507. doi: 10.1076/clin.15.4.498.1882. PMID 11935451

• Danna L Jennings, MD, Principal investigator, Institute for Neurodegenerative Disorders