Neurostimulation and Cognitive Intervention in Alzheimer's Disease

Study Overview
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Brief Summary
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This study is a double blind, sham-controlled clinical trial aiming to compare the long-term effects of stimulation in Alzheimer's Disease (AD). Sixty early AD patients will take part in a phase II/III clinical study over a 1-year period. The study involves transcranial direct current stimulation (tDCS), cognitive training (CT), detailed neuropsychological and neurological testing. These assessments will occur at baseline, then again at two month (end point). Those who achieve clinical improvement with neurostimulation and cognitive therapy will be invited to receive treatment for 12 months as part of a follow-up study.

Detailed Description
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The patients will be randomized into 1 of 4 groups: active tDCS plus real CT, active tDCS plus placebo CT, sham tDCS plus real CT, sham tDCS plus placebo CT. Each group will receive treatment for 30 minutes a day, 3 days a week for 8 weeks.

Official Title
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Neurostimulation and Cognitive Intervention in Alzheimer's Disease

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Device: active tDCS
* Device: sham tDCS
* Behavioral: real CT
* Behavioral: placebo CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female age 60-90 years Patients diagnosed with Alzheimer's Disease, according to the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) and NINCDS-ADRDA (National Institute for Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association) criteria Score between 18 and 26 on the Mini Mental State Examination Have a CDR (Clinical Dementia Rating) of 1.0 If medicated for AD, then use of cholinesterase inhibitors, for at least 3 months and on stable dose for at least 60 days prior to screening. Exclusion Criteria: Pre-existing structural brain abnormalities, Other neurologic or psychiatric diagnoses Transcranial direct current stimulation criteria: patients with implanted metallic or electronic devices; pacemaker; seizures; pregnancy; any other condition that might limit or interfere in the sensorimotor system

Ages Eligible for Study
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Minimum Age: 60 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: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: active tDCS plus real CT<br>Participants will receive active transcranial direct current stimulation and real cognitive training. | Device: active tDCS<br>* Duration: 30 minutes; Intensity: 2 mA; Placement:left and right parietal cortex, left and right DLPFC, left inferior frontal gyrus and left superior temporal gyrus<br>Behavioral: real CT<br>* Cognitive tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left inferior frontal gyrus and left superior temporal gyrus).<br>|
| Experimental: sham tDCS plus real CT<br>Participants will receive sham transcranial direct current stimulation and real cognitive training. | Device: sham tDCS<br>* The procedure is the same as for active tDCS, but the in the placebo tDCS the stimulation is non-active / sham.<br>Behavioral: real CT<br>* Cognitive tasks designed to relate to the region of the brain being stimulated (left and right parietal cortex, left and right DLPFC, left inferior frontal gyrus and left superior temporal gyrus).<br>|
| Experimental: active tDCS plus placebo CT<br>Participants will receive active transcranial direct current stimulation and placebo cognitive training. | Device: active tDCS<br>* Duration: 30 minutes; Intensity: 2 mA; Placement:left and right parietal cortex, left and right DLPFC, left inferior frontal gyrus and left superior temporal gyrus<br>Behavioral: placebo CT<br>* Videos (short films) will be presented during the neurostimulation<br>|
| Placebo Comparator: sham tDCS plus placebo CT<br>Participants will receive sham transcranial direct current stimulation and placebo cognitive training. | Device: sham tDCS<br>* The procedure is the same as for active tDCS, but the in the placebo tDCS the stimulation is non-active / sham.<br>Behavioral: placebo CT<br>* Videos (short films) will be presented during the neurostimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive function assessed on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) |  | Baseline (week 1), Endpoint (week 8) and Follow up (assessed up to 12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive ability assessed on the Wechsler Adult Intelligence Scale |  | Baseline (week 1), Endpoint (week 8) and Follow up (assessed up to 12 months) | 
| Change in visuo-spatial working memory assessed on the Corsi block task |  | Baseline (week 1), Endpoint (week 8) and Follow up (assessed up to 12 months) | 
| Change in verbal working memory assessed on the Digit Span task |  | Baseline (week 1), Endpoint (week 8) and Follow up (assessed up to 12 months) | 
| Change in speed of cognitive processing and executive functioning assessed on the Trail Making Test |  | Baseline (week 1), Endpoint (week 8) and Follow up (assessed up to 12 months) | 
| Change in executive function assessed on the Stroop Color and Word Test |  | Baseline (week 1), Endpoint (week 8) and Follow up (assessed up to 12 months) | 
| Change in verbal fluency assessed on the FAS Verbal Fluency Test |  | Baseline (week 1), Endpoint (week 8) and Follow up (assessed up to 12 months) | 
| Change in functional ability assessed on the Disability Assessment Dementia |  | Baseline (week 1), Endpoint (week 8) and Follow up (assessed up to 12 months) | 
| Change in visual recognition assessed on the Poppelreuter-Ghent's Overlapping Figures test |  | Baseline (week 1), Endpoint (week 8) and Follow up (assessed up to 12 months) | 
| Change in behavioral and psychological disturbances assessed on the Neuropsychiatric Inventory Questionnaire |  | Baseline (week 1), Endpoint (week 8) and Follow up (assessed up to 12 months) | 
| Change in subjective burden among caregivers assessed on the Zarit Burden Interview |  | Baseline (week 1), Endpoint (week 8) and Follow up (assessed up to 12 months) | 
| Change in electrical activity of the brain assessed on the Electroencephalogram (EEG) |  | Baseline (week 1), Endpoint (week 8) and Follow up (assessed up to 12 months) | 
| Side Effects Questionnaire |  | From date of first neurostimulation until the date of last neurostimulation, assessed up to 12 months |