Effects of Donepezil HCL on Task-Activated fMRI Brain Activation in Healthy Older Adults at Genetic Risk for Alzheimer's Disease

Study Overview
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Brief Summary
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This study examines the sensitivity of functional MRI to detect brain changes caused by donepezil HCL (a cholinesterase inhibitor) in healthy older adults at genetic risk for Alzheimer's Disease.

Detailed Description
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This 24-week study will examine the sensitivity of functional MRI to detect brain changes caused by donepezil HCL (a cholinesterase inhibitor) in healthy older adults at genetic risk for Alzheimer's Disease. Participants with a family history of Alzheimer's Disease will be eligible for this study. Participants without a family history of AD will also be enrolled to serve as a control group.

Official Title
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Effects of Donepezil HCL on Task-Activated fMRI Brain Activation in Healthy Older Adults at Genetic Risk for Alzheimer's Disease

Conditions
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Genetic Risk for Alzheimer's Disease

Intervention / Treatment
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* Drug: donepezil HCL
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal general cognitive function High Risk Group Only: Family history (1st degree relative) of AD Low Risk Group Only: No family history (1st or 2nd degree relative) of AD Visual and auditory acuity adequate for neuropsychological testing Exclusion Criteria: Current or past history of neurological illnesses/conditions head trauma with significant loss of consciousness medical illnesses/conditions that may affect brain function severe psychiatric disorder substance abuse unstable or severe cardiovascular disease or asthmatic condition history of stroke or transient ischemic attack

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 75 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

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Donepezil HCL<br>Participants will receive 5mg of donepezil HCL for 4 weeks and then 10mg of donepezil HCL for 20 weeks. | Drug: donepezil HCL<br> <br> |
| Placebo Comparator: Placebo<br>Participants will receive placebo for 24 weeks. | Drug: Placebo<br> <br> |
| No Intervention: Control Group<br>Participants without a family history of AD will undergo the study evaluations but will not receive any study drug | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BOLD Response From Baseline to 24 Weeks During Functional Magnetic Resonance Imaging - Left Posterior Cingulate BOLD Signal at 24 Weeks, Adjusting for Baseline Left Posterior Cingulate BOLD | Changes from baseline to 24 weeks follow-up fMRI - Left posterior cingulate BOLD signal at 24 weeks, adjusting for baseline left posterior cingulate BOLD signal. | Baseline and 24 Weeks | 
| Left Hippocampus BOLD Signal at 24 Weeks, Adjusted for Baseline Left Hippocampus BOLD Signal | Left hippocampus BOLD signal at 24 weeks, adjusting for baseline left hippocampus BOLD signal. | Baseline and 24 Weeks | 
| Right Hippocampus BOLD Signal at 24 Weeks, Adjusted for Baseline Left Hippocampus BOLD Signal | Right hippocampus BOLD signal at 24 weeks, adjusting for baseline left hippocampus BOLD signal. | Baseline and 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropsychological Testing Scores - Rey Auditory Verbal Learning Test (RAVLT) Sum of Trials (1-5) at 24 Weeks, Adjusted for Baseline RAVLT Score | Rey Auditory Verbal Learning Test (RAVLT) (Sum of Trials 1-5) , adjusting for baseline RAVLT (Sum of Trials 1-5) score. The RAVLT total score has a minimum of 0 and a maximum of 75 correct items (15 per trial x 5 trials). A higher score means better outcomes. | Baseline and 24 Weeks | 
| Left Hippocampus Volume (MRI) at 24 Weeks, Adjusted for Baseline Left Hippocampus Volume | Left hippocampus volume (MRI) at 24 weeks, adjusting for baseline left hippocampus volume | Baseline and 24 Weeks | 
| Right Hippocampus Volume (MRI) at 24 Weeks, Adjusted for Baseline Right Hippocampus Volume | Right hippocampus volume (MRI) at 24 weeks, adjusting for baseline right hippocampus volume | Baseline and 24 Weeks | 
| Brief Visuospatial Memory Test (BVMT) Learning Scores at 24 Weeks, Adjusted for Baseline BVMT Learning Scores | Brief Visuospatial Memory Test (BVMT) learning scores at 24 weeks, adjusted for baseline BVMT learning scores. The BVMT-R total scare has a minimum of 0 and a maximum of 36 correct items (12 per trial x 3 trials). A higher score means better outcomes. | Baseline and 24 Weeks | 
| Processing Speed Test (PST) at 24 Weeks, Adjusted for Baseline PST Scores | Processing speed test (PST) at 24 weeks, adjusting for baseline PST scores. The PST has a minimum of 0 and no upper limit/maximum since it is the number of correct items in 2 minutes. A higher score means better outcome. | Baseline and 24 Weeks |