Deep Brain Stimulation for Alzheimer's Disease

Study Overview
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Brief Summary
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Background: Deep brain stimulation (DBS) is used to modulate the activity of dysfunctional brain circuits. The safety and preliminary efficacy of nucleus basalis of Meynert (NBM)-DBS in Alzheimer's disease (AD) is proved in a recent phase 1 clinical trial, yet, the mechanism still unknown. Objective: 1. To compare the brain structure and functional circuits between a) AD patients with optimal drug treatment (ODT) plus NBM-DBS, b) AD with ODT and c) normal age-and sex-matched control. 2. To evaluate the clinical effectiveness of NBM-DBS in AD patients 60-75 year-old. 3. To evaluate the abnormal functional circuitry response to acute and chronic NBM-DBS in AD. Methods: A total of 30 subjects (10 subjects of AD with ODT plus NBM-DBS; 10 subjects of AD with ODT and 10 subjects of normal age-and sex-matched subjects) will be enrolled in this prospective, with normal control, Phase II study. Study tools will include clinical rating batteries, structure and functional imaging of magnetic resonance (MR) and positron emission tomography (PET), and electroencephalogram (EEG). Expected Results: NBM-DBS will be proved to be an safe and effective treatment modality in AD patients 60-75 year-old. Through multi-modal images and EEG analysis, the possible action mechanisms of NBM-DBS on memory circuit will be discussed. The study results may shed a light on this helpless neurodegenerative disease of dementia.

Official Title
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The Effect of Deep Brain Stimulation on Memory Network and Neurological Function of Alzheimer's Disease

Conditions
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Alzheimer Disease, Dementia, Alzheimer Type, Deep Brain Stimulation

Intervention / Treatment
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* Device: Deep brain stimulation
* Drug: Best medical treatment for Alzheimer's disease


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For groups (AD with/ without DBS) Confirmed Alzheimer's dementia diagnosis Regular medications taking for at least 3 months Clinical Dementia Rating: 0.5 - 2 Mini Mental Status Examination: ≦ 26 Amyloid PET: positive Informed consent signed by patients or families For normal control group No cognitive impairment (Mini Mental Status Examination) Amyloid PET: negative Informed consent signed by patients and families Exclusion Criteria: For groups (AD with/ without DBS) Structural lesions identified by Magnetic resonance imaging (ex: stroke, brain surgery) Other neurodegenerative/ neuropsychiatric diseases Systemic medical diseases with cognitive impairment (ex: anemia, thyroid disease) Can't have regular follow-up visit For normal control group Structural lesions identified by Magnetic resonance imaging (ex: stroke, brain surgery) Dementia/ neurodegenerative/ neuropsychiatric diseases Systemic medical diseases with cognitive impairment (ex: anemia, thyroid disease) Can't have regular follow-up visit

Ages Eligible for Study
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Minimum Age: 50 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

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AD with DBS<br>Alzheimer's disease subjects with optimal medication therapy and with DBS treatment | Device: Deep brain stimulation<br>* Brain stimulation electrodes at parameters 2.0 4.5 V；60 μs；20 Hz<br>* Other names: Deep brain stimulation electrodes (Medtronic or Abbott);Drug: Best medical treatment for Alzheimer's disease<br>* Alzheimer's disease patients take medications including Exelon (Rivastigmine Tartrate), Witgen (Memantine) for at least 3 months without plan of dosage adjustment<br>* Other names: Exelon (Rivastigmine Tartrate), Witgen (Memantine);|
| Active Comparator: AD without DBS<br>Alzheimer's disease subjects with optimal medication therapy and without DBS treatment | Drug: Best medical treatment for Alzheimer's disease<br>* Alzheimer's disease patients take medications including Exelon (Rivastigmine Tartrate), Witgen (Memantine) for at least 3 months without plan of dosage adjustment<br>* Other names: Exelon (Rivastigmine Tartrate), Witgen (Memantine);|
| No Intervention: Normal control<br>Matched aged and demographics subjects | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) | Change from baseline in Alzheimer's Disease Assessment Scale-cognitive subscale; Total scores range from 0-70. Higher scores (≥ 18) indicate worse cognitive function. It consists of 11 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities. | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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magnetic resonance image