Cognitive Changes in Alzheimer's Disease Patients Associated With or Without White Matter Changes After Rivastigmine

Study Overview
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Brief Summary
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The purpose of this study is to evaluate and compare the changes of cognitive function (as measured by ADAS-Cog) in the two group of patients with Alzheimer's disease (AD) associated with and without white matter changes after rivastigmine patch therapy.

Detailed Description
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Acetylcholinesterase inhibitors (AChEIs) increase the amount acetylcholine at ACh receptors within the brain, and are the primary medications used to treat AD. Alzheimer's disease patients are frequently associated with mild or moderate white matter changes on MR imaging. The impact of whiter matter changes on the efficacy of cognition, functional abilities, behavioral and psychiatric symptoms and caregiver burden for probable Alzheimer's disease is not well known. There are very few studies for the efficacy of rivastigmine between the patients with mild to moderate Alzheimer's disease associated with or without vascular risk factors. Recently, the rivastigmine patch demonstrated efficacy comparable to the highest doses of rivastigmine capsules, with markedly improved tolerability profile. The investigators hypothesized that rivastigmine patch will provide benefits to AD patients with white matter changes compared to those without any white matter changes. Possible explanation about favorable benefits for AD with white matter changes is that rivastigmine may act on both Alzheimer's and vascular pathologies contributing to dementia, providing additive treatment effects in patients suffering from both conditions concurrently. To our Knowledge, there was no study or clinical trial to compare the changes of cognitive function, ADL, BPSD and caregiver burden in two groups of patient with Alzheimer's disease associated with or without white matter changes after rivastigmine transdermal patch therapy.

Official Title
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Changes of Cognitive Function in Patients With Mild to Moderate Alzheimer's Disease Associated With or Without White Matter Changes After Rivastigmine Patch Therapy - Multi-center, Prospective, Open-label Clinical Trial

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: rivastigmine patch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: AD in NINCDS-ADRDA criteria, mild to moderate probable AD with or without mild to moderate whiter matter lesions, excluding multiple large vessel infarcts or a single, strategically placed infarct (angular gyrus, thalamus, basal forebrain, territory of the posterior or anterior cerebral artery) on MRI scan (within 12 months) MMSE score : 10 to 26 at screening Hachinski scores ≤ 4 No clinically significant laboratory abnormalities, such as thyroid disease, vitamine B12 deficiency or folic acid deficiency Exclusion Criteria: Current evidence of history of neurological, psychiatric and other illness that could contribute to dementia Subjects with clinical significant cardiovascular disease, stroke, pulmonary disease or any other medical disease in the past 6 months History of cancer within the last 5 years Subjects with evidence or history of clinically significant allergic reaction to AchEI or drugs Subjects who had significant visual or hearing difficulties

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: without white matter change<br> | Drug: rivastigmine patch<br>* rivastigmine patch 5cm2 for 4 weeks and then augmented to 10cm2 for 20 weeks<br>* Other names: Exelon patch;|
| Active Comparator: with white matter change group<br> | Drug: rivastigmine patch<br>* rivastigmine patch 5cm2 for 4 weeks and then augmented to 10cm2 for 20 weeks<br>* Other names: Exelon patch;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changes of cognitive function as measured by ADAS-Cog |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MMSE (Mini-Mental State Examination) |  | 24 weeks | 
| Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) |  | 24 weeks | 
| Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) |  | 24 weeks | 
| Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI) |  | 24 weeks | 
| Caregiver burden scale |  | 24 weeks | 
| Adverse events |  | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's disease, rivastigmine patch, white matter change