Imaging a Cholinergic Biomarker of Cognition in Parkinson's Disease

Stony Brook University6 enrolled

Overview

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.

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

Conditions

Parkinson's Disease

Eligibility

Sex: ALLMin age: 50 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (1)

Stony Brook Medical Center

Stony Brook, New York, United States

Outcomes

Primary Outcomes

Cholinergic terminal density at baseline

Measured by PET scan 18F\[VAT\] distribution volume

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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Time frame: Baseline

Attention/working memory change from baseline to 18-months follow-up as measured by the Trail Making A Test

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline and 18-month follow-up

Executive function at baseline as measured by the Trail Making Test B

Time frame: Baseline

Executive function change from baseline to 18-months follow-up as measured by the Trail Making Test B

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: Baseline

Progesterone levels in blood as baseline

Progesterone levels (nanograms of progesterone per milliliter of serum) will be measured via blood draw at baseline

Time frame: 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.

Time frame: Baseline

Secondary Outcomes

Cholinergic terminal binding potential at baseline

Measured by PFC \[18F\]VAT VT and BPND

Time frame: Baseline

Cholinergic terminal binding potential change between baseline and 18-months follow-up

Measured by PFC \[18F\]VAT VT and BPND

Time frame: Baseline and 18-month follow-up

MRI Fractional anisotropy (FA) Values at baseline

As measured by fMRI at baseline

Time frame: 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

Time frame: Baseline and 18-months follow-up

MRI Resting-state functional connectivity at baseline

As measured by fMRI

Time frame: Baseline

MRI Resting-state functional connectivity change between baseline and 18-months follow-up

As measured by fMRI

Time frame: Baseline and 18-months follow-up