JMIR Publications

ABSTRACT

Background:

Alzheimer’s disease has no known cure. As existing pharmacologic interventions only modestly slow cognitive decline, there is a need for new treatments. Recent trials of repetitive transcranial stimulation (rTMS) have reported encouraging results for improving or stabilizing cognition in patients diagnosed with Alzheimer’s dementia. However, due to small samples and lack of a well-controlled double-blind design, the results to date are inconclusive. This paper presents the protocol of a large placebo-controlled double-blind study designed with sufficient statistical rigor to measure the efficacy of rTMS treatment in Alzheimer’s dementia.

Objective:

The objectives are to: 1) estimate the difference in treatment effects among patients treated with active as compared with sham, 2) estimate the difference in treatment effects two doses of rTMS, 3) estimate the duration of treatment effects amongst responders to active rTMS, and 4) estimate the effect of dementia severity on treatment outcome among patients receiving active rTMS.

Methods:

We have designed our study to be a double-blind, randomized placebo controlled clinical trial investigating the short- and long-term (up to 6 months) benefit of active rTMS treatment at two doses (either 10 sessions over 2 weeks or 20 sessions over 4 weeks) compared to sham rTMS. The primary outcome measure is the change in Alzheimer Disease Assessment Scale, Cognitive subsection (ADAS-Cog) score from pre- to post- treatment. Secondary outcomes are the changes in performance on tests of frontal lobe functioning (Stroop test, verbal fluency), in neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire) and in activities of daily living (Alzheimer’s Disease Co-operative Study - Activities of Daily Living Inventory). Tolerability of the intervention will be assessed using a modification of the Treatment Satisfaction Questionnaire for Medication (TSQM). We assess participants at baseline, after three and five weeks of intervention, and at 8, 16 and 24 weeks post-intervention.

Results:

We anticipate that rTMS will significantly improve cognitive function, with effects lasting up to 3 months. Also we expect rTMS to be a well tolerated treatment with no serious side effect.

Conclusions:

This design of the protocol will allow to address both the rTMS active treatment dose and its short- and long-term effects compared to sham in large samples. Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02908815