Neural Correlates In Mild Alzheimer's Disease

Study Overview
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Brief Summary
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The objective of this study was to identify neural correlates of cognitive improvement after 3 months of donepezil hydrochloride treatment using either or both of two functional magnetic resonance imaging (fMRI) measures - the functional Hippocampus Connectivity Index (HCI) and Cerebral Blood Flow (CBF) Perfusion; in the Medial Temporal Lobe (MTL) network in subjects in the early stage of Alzheimer's Disease (AD).

Official Title
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A Single Center Study To Examine Neural Correlates Of Cognition In Subjects With Mild Alzheimer's Disease After Three Months Of Open Label Donepezil HCl (Aricept® ) Treatment

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Donepezil hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women, aged 50 and older with mild Alzheimer's disease (MMSE scores of 20 to 30 are allowed). Diagnostic evidence of Alzheimer's disease. Previous use of cholinesterase inhibitors (other than Aricept) and memantine allowed. Exclusion Criteria: Prior use of Aricept, pacemakers and insulin dependent diabetes are not allowed.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donepezil hydrochloride<br> | Drug: Donepezil hydrochloride<br>* Donepezil hydrochloride 5 mg per day orally, once daily for 4 weeks, followed by 10 mg per day (two 5-mg tablets) for 8 weeks<br>* Other names: E2020, Aricept;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 12 Based on Hippocampus Connectivity Index (HCI) | All neuroimaging procedures were performed on a research-dedicated GE 3.0 Tesla whole-body Excite scanner with 8-channel phase-array head coil. Resting-state functional magnetic resonance imaging (fMRI) of the medial temporal lobe (MTL) was performed. The functional HCI was derived from the MTL network using a data driven approach corresponding voxel time courses from the fMR images were processed to extract low frequency fluctuations. Functional connectivity was quantified by calculating the cross-correlation of each voxel time course in the hippocampus to all voxel time courses of the whole brain and the mean of absolute cross-correlation coefficients between a hippocampus voxel to the whole-brain voxels. HCI was then calculated as the average of all hippocampus cross-correlation coefficients. Change from baseline (CFB) was calculated using the CBF-Perfusion Processing Method. A positive change from baseline for HCI indicates improved function. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline at Week 12 in Alzheimer's Disease Assessment Scale - Cognitive Scale (ADAS)-Cog Score | The ADAS-cog is a 13-item performance-based test that examines selected aspects of cognition including memory, orientation, attention, reasoning, language, and praxis. Total score ranges from 0 to 70 with higher scores indicating greater cognitive impairment. A decrease from baseline indicates improved cognitive function. The ADAS-cog was administered by a trained individual unaware of adverse events reported during this trial. | Baseline and Week 12 | 
| Change From Baseline at Week 12 in Mini-Mental State Examination (MMSE) Score | MMSE was a 11-item scale to measure cognitive status where a higher score indicated better cognitive state. The score ranged from 0 to 30, with a higher score indicating better function. A positive change score indicated improvement from baseline. The mean change was analyzed by Wilcoxon's signed rank test. | Baseline and Week 12 | 
| Change From Baseline at Week 12 in the Instrumental Activities of Daily Living (IADL) Assessment Score | IADL Scale measures 7 areas of more complex activities required for optimal independent functioning, as reported by the caregiver. The scoring indicates whether the participant was completely independent (3), requires assistance (2), or is dependent (1) for the performance of each activity. A summary score ranges from 7 (high function, independent) to 21 (low function, dependent). The mean change was analyzed by Wilcoxon's signed rank test. A decrease from Baseline to Week 12 indicates improved function. | Baseline and Week 12 | 
| Change From Baseline at Week 12 in the Neuropsychiatric Inventory (NPI) Score | NPI was a 12-item caregiver-based assessment of behavioral disturbances commonly occurring in participants with AD. NPI includes 12 sections which are Delusions, Hallucinations, Agitation, Depression, Anxiety, Euphoria, Apathy, Disinhibition, Irritability, Aberrant motor behavior, Night-time behaviors and Appetite and eating disorders. The score of each section ranges from 0 to 12, and higher score means higher severity and frequency of the neuropsychiatric disturbances. The mean change was analyzed by Wilcoxon's signed rank test. | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Functional magnetic resonance imaging examination, Alzheimer's Disease, Donepezil hydrochloride, Aricept