Repetitive Transcranial Magnetic Stimulation for Dementia

Study Overview
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Brief Summary
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The purpose is to is to study if repetitive transcranial magnetic stimulation (rTMS) improves cognitive function in patients with neurodegenerative conditions which may manifest as mild to moderate cognitive impairment and, in late phase, dementia. This study also intends to investigate if the responses to rTMS intervention are either positively or negatively correlated with the initial severity of cognitive impairment.

Detailed Description
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The primary hypothesis is that rTMS applied to the dorsolateral prefrontal cortex will lead to improved memory, language and executive function compared to patients who receive a sham, control treatment. The improvement is defined as having higher performance on the California Verbal Learning Test (CVLT-II). Secondary Hypotheses are that: 1: rTMS- will lead to higher performance on secondary cognitive measures relating to executive function and naming compared to performance by participants in the sham treatment group at the termination of treatment; and that 2: rTMS-induced memory improvement parallels changes in serum and cerebrospinal fluid (CSF) brain-derived neurotrophic factor (BDNF) levels after treatment.

Official Title
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Repetitive Transcranial Magnetic Stimulation for Dementia

Conditions
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Mild Cognitive Impairment, Dementia

Intervention / Treatment
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* Device: RTMS
* Device: sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Veterans aged 55 years or older Diagnosed with Mild Cognitive Impairment (MCI) or dementia likely due to Alzheimer's disease. Ability to obtain a Motor Threshold, determined during the screening process. With an adequately stable condition and living environment to enable attendance at scheduled clinic visits. If on a prescription medication for cognition that medication dose will be stable for at least 4 weeks prior to randomization into the study and participant will be willing to remain on a stable regimen during the acute treatment phase. Able to read, verbalize understanding, and voluntarily sign the Informed Consent Form to be signed by the participant, or a designated legal representative when the participant lacks decision making capacity prior to participating in any study- specific procedures or assessments. Exclusion Criteria: Patients with prior exposure to rTMS or electroconvulsive therapy (ECT). Unable to safely withdraw, at least two weeks prior to treatment commencement, from medications that substantially increase the risk of having seizures. Have a cardiac pacemaker or a cochlear implant. Have an implanted device deep brain stimulation or metal in the brain Current substance abuse not including caffeine or nicotine as determined by patient report or chart review. Active current suicidal intent or plan as determined by patient report or chart review. Current or Prior history of a seizure disorder as determined by patient report or chart review Traumatic brain injury within the last two months Participation in another concurrent interventional clinical trial Known current psychosis as determined by patient report or chart review. Current or prior history of a mass lesion, cerebral infarct or other non-cognitive, active central nervous system (CNS) disease that would increase the risk for seizure. Not fluent in English or a hearing impairment severe enough to impair comprehension

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 99 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RTMS<br>repetitive transcranial magnetic stimulation | Device: RTMS<br>* stimulation of the brain with magnetic pulses<br>|
| Sham Comparator: sham<br>sham noise to block the sound of treatment | Device: sham<br>* sham noise to block the sound of stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes From Baseline CVLT Scores After Treatment and 4 Month Later | Changes of California verbal learning test scores (CVLT) from baseline after treatment and 4 months later. CVLT is 16 points scoring system. (minimum=0, maximum=16, higher the better memory). | Assessed at baseline, end of treatment, and 4-month post-treatment follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Boston Naming After Treatment | Changes in Boston Naming Test (BNT) from baseline was analyzed. BNT is a 60 points scoring system. (minimum=0, maximum=60, higher the better). | Assessed at baseline, end of treatment, and 4-month post-treatment follow up | 
| Changes in Plasma BDNF Levels After Treatment | Changes in BDNF plasma levels (pg/ml) from baseline were analyzed after treatment. BDNF is a plasma biomarker, minimum=0, no maximum. Higher number means more BDNF synthesis). | within a week following the last treatment session and 4 months later | 
| Changes in Animal Fluency After Treatment and 4 Months Later | Animal Fluency (AF) is a scoring system to assess the ability to generate a list of related words. The score is the number of animals the examinee can name in one minute time. (Minimum = 0, No maximum, higher the better). | Assessed at baseline, end of treatment, and 4-month post-treatment follow up | 
| Changes in Trail Making B Test Score After Treatment and 4 Months Later | Trail making B is a scoring system for the assessment of the mental flexibility, processing speed and executive function. The score is the time (in seconds) it takes for the examinee to draw line segments connecting sequentially from 1-A-2-B-3....all the way to12-L-13. (The lower score means faster speed and means better performance. The minimum is (hypothetically) zero. There is no maximum. However, in some test centers, the maximum allowed time is 200 seconds. | Assessed at baseline, end of treatment, and 4-month post-treatment follow up | 
| Brief Visual Memory Test (BVMT) | A piece of paper with 6 simple drawings is presented to the subject for 10 seconds. The subject is then asked to draw these drawings from memory. The process is repeated three times to assess visual memory and learning. Each correct drawing scores two pints. Maximum score for three trials is 36. Minimum score is 0. Higher the better. | assessed at baseline, end of treatment and 4-month post-treatment follow up | 
| Montreal Cognitive Assessment (MoCA) | MoCA is a one page, 30 point cognitive screening test. It test the following cognitive domains: short-term memory (5 points)- two learning trials of five nouns and delayed recall after approximately five minutes. visuospatial abilities - clock-drawing task (3 points) and copy a cube (1 point). executive functions - alternation task abbreviated trail-making B (1 point), and a two-item verbal abstraction task (2 points). attention, concentration, and working memory - a sustained attention task (target detection using tapping; 1 point), a serial subtraction task (3 points), and digits forward and backward (1 point each). language - three-item confrontation naming (3 points), repetition of two sentences (2 points), and verbal fluency (1 point). abstract reasoning - describe the similarity of tasks (2 points). orientation to time and place (6 points). Minimum score: 0. Maximum score: 30. Higher the better. | Assessed at baseline, end of treatment, and 4-month post-treatment follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dementia, Mild Cognitive Impairment (MCI), RTMS, CVLT