Imaging a Cholinergic Biomarker of Cognition in Parkinson's Disease

This is an imaging study designed to illuminate the function of the cholinergic system and its association with cognitive skills in people with Parkinson's disease. The hypothesis of this study is that there will be an association between cholinergic terminal density, sex hormones, and cognitive functioning. Participants will receive a PET and MRI scan along with a battery of neurocognitive tests at baseline and again at 18 months follow-up. Hormone levels will be measured at baseline.

Study Overview

• Status: Recruiting
• Conditions: Parkinson's Disease

Detailed Description

This is an imaging study designed to illuminate the functioning of the cholinergic system in people with Parkinson's disease. Some people with Parkinson's disease develop trouble with certain aspects of thinking such as memory. Studies have shown an association between a decline in thinking skills and dysfunction of the cholinergic system. This study will use the novel PET tracer [18F]VAT to provide more specific information about how the cholinergic system works by enabling direct measurement of cholinergic terminal density and projections. The hypothesis of this study is that there will be an association between cholinergic terminal density, sex hormones, and cognitive functioning. This is a longitudinal observational study that involves a screening visit and four study visits over the course of 18 months. The visits consist of neurocognitive assessments and imaging (MRI and PET scans) administered at baseline and at 18 months follow-up. Hormone levels will also be measured at baseline. This study is open to people with Parkinson's disease who have either normal cognition or mild cognitive impairment.

• Study Type: Observational
• Enrollment (Anticipated): 15

Contacts and Locations

• Study Contact: Name: Sandra Skinner, PhD; Phone Number: 631-444-7513; Email: sandra.skinner@stonybrookmedicine.edu

Study Locations

• United States
  • New York
    • Stony Brook, New York, United States, 11794
      • Recruiting
      • Stony Brook Medical Center
      • Contact: Sandra Skinner, PhD; Phone Number: 631-444-7513; Email: sandra.skinner@stonybrookmedicine.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

People with Parkinson's disease who have normal cognition or mild cognitive impairment

Description

Inclusion Criteria:

• Age 50-80
• Diagnosis of Parkinson's disease
• Ability to provide informed consent
• Ability to speak English
• Normal cognition or mild cognitive impairment
• Willingness to go off parkinsonian medication for 12 hours prior to two of the study visits

Exclusion Criteria:

• Contraindication for MRI
• Abnormal clinical brain MRI, specifically with evidence of large-vessel stroke or mass lesion
• History of stereotactic or ablative brain surgery
• Pregnancy
• Recent participation in other research studies involving radiation such that the annual research radiation dose would exceed FDA Limit if participating in this study
• Prior brain injury (eg., TBI)
• Baseline cognitive impairment due to genetic or developmental disorder
• Active illicit drug use or alcohol abuse
• Incapable of staying still for a 2-hour PET or MRI study
• Use of CNS-penetrating medications affecting the cholinergic system, including cholinesterase inhibitors and anticholinergics, up to 60 days prior to study participation

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cholinergic terminal density at baseline	Measured by PET scan 18F[VAT] distribution volume	Baseline
Cholinergic terminal density change between baseline and 18-months follow-up	Measured by the difference in PET scan 18F[VAT] distribution volume at baseline and 18-months follow-up	Baseline and 18 months follow-up
Overall cognitive functioning at baseline	As measured by the Montreal Cognitive Assessment (MoCA). The MoCA measures eight domains commonly affected by mild cognitive impairment. The one-page 30-point test includes assessments of short-term and delayed memory recall, visuospatial abilities, language, orientation to time and space, and executive functions including attention, concentration, and working memory. The MoCA has been shown to be sensitive to change over time. Scores on the MocA range from 0-30 with higher scores indicating better cognitive functioning.	Baseline
Change in overall cognitive functioning	As measured by the difference between the Montreal Cognitive Assessment (MoCA) score at baseline and at 18-months follow-up.The MoCA measures eight domains commonly affected by mild cognitive impairment. The one-page 30-point test includes assessments of short-term and delayed memory recall, visuospatial abilities, language, orientation to time and space, and executive functions including attention, concentration, and working memory. The MoCA has been shown to be sensitive to change over time. Scores on the MocA range from 0-30 with higher scores indicating better cognitive functioning.	Baseline and 18 Months
Attention/working memory at baseline as measured by the Trail Making A Test	The Trail Making Test is a quickly and easily administered test which assesses cognitive abilities such as visual-conceptual and visual-motor tracking, sustained attention, and task alternation abilities. Administration time for the Trail Making Test A is 5 minutes.	Baseline
Attention/working memory change from baseline to 18-months follow-up as measured by the Trail Making A Test	The Trail Making Test is a quickly and easily administered test which assesses cognitive abilities such as visual-conceptual and visual-motor tracking, sustained attention, and task alternation abilities. Administration time for the Trail Making Test A is 5 minutes.	18 months
Attention/working memory at baseline as measured by the Symbol Digit Modalities Test (SDMT)	Symbol Digit Modalities Test (SDMT) takes five minutes to complete and has demonstrated sensitivity in detecting changes in cognitive functioning over time.	Baseline
Attention/working memory change from baseline to 18-months follow-up as measured by the Symbol Digit Modalities Test	Symbol Digit Modalities Test (SDMT) takes five minutes to complete and has demonstrated sensitivity in detecting changes in cognitive functioning over time.	Baseline and 18- months follow-up
Executive function at baseline as measured by the Clock Drawing Test	The Clock Drawing Test is a quick screening test for cognitive dysfunction secondary to a range of neurological disorders and takes less than 5 minutes to administer.	Baseline
Executive function change from baseline to 18-months follow-up as measured by the Clock Drawing Test	The Clock Drawing Test is a quick screening test for cognitive dysfunction secondary to a range of neurological disorders and takes less than 5 minutes to administer.	Baseline and 18-month follow-up
Executive function at baseline as measured by the Trail Making Test B	The Trail Making Test is a quickly and easily administered test which assesses cognitive abilities such as visual-conceptual and visual-motor tracking, sustained attention, and task alternation abilities. Administration time for the Trail Making Test B is 10 minutes.	Baseline
Executive function change from baseline to 18-months follow-up as measured by the Trail Making Test B	The Trail Making Test is a quickly and easily administered test which assesses cognitive abilities such as visual-conceptual and visual-motor tracking, sustained attention, and task alternation abilities. Administration time for the Trail Making Test B is 10 minutes.	Baseline and 18-month follow-up
Language at baseline as measured by the Animal Naming Test	The Animal Naming Test is a semantic fluency test that takes one minute to administer.	Baseline
Language change from baseline to 18-month follow-up as measured by the Animal Naming Test	The Animal Naming Test is a semantic fluency test that takes one minute to administer.	Baseline and 18-months follow-up
Language at baseline as measured by the Boston Naming Test	The Boston Naming Test measures confrontational word retrieval and takes about 15 minutes to administer.	Baseline
Language change from baseline to 18-months follow-up as measured by the Boston Naming Test	The Boston Naming Test measures confrontational word retrieval and takes about 15 minutes to administer.	Baseline and 18-months follow-up
Language change between baseline and 18-month follow-up as measured by the Boston Naming Test	The Boston Naming Test measures confrontational word retrieval and takes about 15 minutes to administer.	Baseline
Memory at baseline as measured by the Free and Cued Selective Reminding Test	The Free and Cued Selective Reminding Test is an episodic memory test which assesses immediate and delayed free and cued-facilitated recall.	Baseline
Memory change from baseline to 18-months follow-up as measured by the Free and Cued Selective Reminding Test	The Free and Cued Selective Reminding Test is an episodic memory test which assesses immediate and delayed free and cued-facilitated recall.	Baseline and 18-months follow-up
Memory at baseline as measured by the Brief Visuospatial Memory Test-Revised Selective Reminding Test	The Brief Visuospatial Memory Test-Revised is a brief measure of visuospatial memory that takes approximately 45 minutes to administer.	Baseline
Memory change from baseline to 18-months follow-up as measured by the Brief Visuospatial Memory Test-Revised	The Brief Visuospatial Memory Test-Revised is a brief measure of visuospatial memory that takes approximately 45 minutes to administer.	Baseline and 18-months follow-up
Memory change between baseline and 18-month follow-up	As measured by the change in Free and Cued Selective Reminding Test and the Brief Visuospatial Memory Test-Revised scores at baseline and at 18-months follow-up.	Baseline and 18-month follow-up
Visuospatial at baseline as measured by the Judgement of Line Orientation Test	Judgement of Line Orientation measures visuospatial perception and takes less than 15 minutes to administer.	Baseline
Visuospatial change from baseline to 18-months follow-up as measured by the Judgement of Line Orientation Test	Judgement of Line Orientation measures visuospatial perception and takes less than 15 minutes to administer.	Baseline and 18-months follow-up
Visuospatial at baseline as measured by the Intersecting Pentagons Test	Intersecting Pentagons is a measure of visuospatial sense that takes less than 5 minutes to administer.	Baseline
Visuospatial change from baseline to 18-months follow-up as measured by the Intersecting Pentagons Test	Intersecting Pentagons is a measure of visuospatial perception that takes less than 5 minutes to administer.	Baseline and 18-months follow-up
Estrogen levels in blood at baseline	Estrogen levels (picograms of estradiol per milliliter of serum) will be measured via blood draw performed at baseline	Baseline
Progesterone levels in blood as baseline	Progesterone levels (nanograms of progesterone per milliliter of serum) will be measured via blood draw at baseline	Baseline
Testosterone levels in blood at baseline	Levels of free testosterone (picograms testosterone per milliliter serum) and total testosterone (nanograms testosterone/deciliter serum) will be measured via blood draw performed at the baseline visit.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cholinergic terminal binding potential at baseline	Measured by PFC [18F]VAT VT and BPND	Baseline
Cholinergic terminal binding potential change between baseline and 18-months follow-up	Measured by PFC [18F]VAT VT and BPND	Baseline and 18-month follow-up
MRI Fractional anisotropy (FA) Values at baseline	As measured by fMRI at baseline	Baseline
Change in MRI Fractional anisotropy (FA) Values from baseline to 18-months follow-up	As measured by fMRI at baseline and 18-months follow-up	Baseline and 18-months follow-up
MRI Resting-state functional connectivity at baseline	As measured by fMRI	Baseline
MRI Resting-state functional connectivity change between baseline and 18-months follow-up	As measured by fMRI	Baseline and 18-months follow-up

Collaborators and Investigators

• Sponsor: Stony Brook University
• Collaborators: Parkinson's Foundation
• Investigators: Principal Investigator: Chuan Huang, PhD, Stony Brook Medical Center; Principal Investigator: Carine Maurer, PhD, Stony Brook Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2021
• Primary Completion (Anticipated): May 27, 2024
• Study Completion (Anticipated): May 27, 2024

Study Registration Dates

• First Submitted: August 17, 2021
• First Submitted That Met QC Criteria: August 27, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): October 25, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: MRI; PET; Acetylcholine
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 2020-00669

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No