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

Sponsor

Hebrew SeniorLife (Other)

Overall Status

Completed

CT.gov ID

NCT01379001

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cholinergic Function	Drug: Scopolamine Drug: Placebo Drug: Donepezil	N/A

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Double (Participant, Investigator)

Official Title:

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

Study Start Date :

Jul 1, 2008

Actual Primary Completion Date :

Jan 1, 2013

Actual Study Completion Date :

Jan 1, 2013

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Young

Young healthy controls, aged 21-35

Drug: Scopolamine

Scopolamine 0.4mg IM x 1 dose; adjustment in older group for weight (0.4mg/70kg)

Drug: Placebo

IM or PO placebo

Experimental: Older

Older healthy controls, aged 65-80

Drug: Scopolamine

Scopolamine 0.4mg IM x 1 dose; adjustment in older group for weight (0.4mg/70kg)

Drug: Placebo

IM or PO placebo

Drug: Donepezil

donepezil 5mg PO x 1

Other Names:

Aricept

Outcome Measures

Primary Outcome Measures

Cerebral blood flow [3 hours]
cerebral blood flow will be measured 3 hours after drug administration using Arterial spin-labeled perfusion MRI

Secondary Outcome Measures

cognitive performance [4 hours]
participants will undergo cognitive testing following drug administration and MRI acquisition

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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