Assessment of Cholinergic and Cognitive Function Using Pharmacologic ASL-Perfusion MRI

Study Overview
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Brief Summary
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This research study will look at how medications affect the pattern of blood flow in the brain. This study will use a special type of MRI (magnetic resonance imaging) scan called perfusion MRI to make measurements of cerebral (brain) blood flow. The medications we will use in this study are scopolamine (commonly used to treat motion sickness), mecamylamine (used to treat high blood pressure), and donepezil (used to treat memory loss). Cognitive testing will also be obtained, and correlated with the blood flow patterns in the brain.

Detailed Description
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Project Summary: This research project will investigate the value of combined pharmacologic manipulation and arterial spin-labeled perfusion MRI (pharmacologic ASL-pMRI) as an in vivo probe of cholinergic function. Methods to investigate cholinergic function in vivo are needed to better understand the role of acetylcholine in the physiology of the cerebral cortex, and in cognitive processes in health and in disease states. In this study, pharmacologic ASL-pMRI will be used to characterize the normal cerebral perfusion response to cholinergic manipulation in young healthy subjects. Cognitive measures will also be obtained and correlated with cerebral perfusion changes. Pharmacologic ASL-pMRI and cognitive testing will then be used to study how the cholinergic response is altered with normal aging and in delirium

Official Title
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Assessment of Cholinergic and Cognitive Function Using Pharmacologic ASL-Perfusion MRI

Conditions
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Cholinergic Function

Intervention / Treatment
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* Drug: Scopolamine
* Drug: Placebo
* Drug: Donepezil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy volunteers Exclusion Criteria: Any neurological condition, such as brain tumor, history of stroke, seizure disorder, attention deficit disorder, normal pressure hydrocephalus, dementia, traumatic brain injury Any major medical conditions, such a cancer, diabetes, glaucoma, prostate disease, uncontrolled hypertension antihistamine use tricyclic antidepressant use presence of metal in body, including pacemaker, defibrillator, neurostimulator, metal implants, or foreign metal objects such as bullets or shrapnel. anxiety or panic disorder history of claustrophobia pregnancy

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Young<br>Young healthy controls, aged 21-35 | Drug: Scopolamine<br>* Scopolamine 0.4mg IM x 1 dose; adjustment in older group for weight (0.4mg/70kg)<br>Drug: Placebo<br>* IM or PO placebo<br>|
| Experimental: Older<br>Older healthy controls, aged 65-80 | Drug: Scopolamine<br>* Scopolamine 0.4mg IM x 1 dose; adjustment in older group for weight (0.4mg/70kg)<br>Drug: Placebo<br>* IM or PO placebo<br>Drug: Donepezil<br>* donepezil 5mg PO x 1<br>* Other names: Aricept;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral blood flow | cerebral blood flow will be measured 3 hours after drug administration using Arterial spin-labeled perfusion MRI | 3 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cognitive performance | participants will undergo cognitive testing following drug administration and MRI acquisition | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cholinergic function, pharmacologic MRI, aging