Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive treatment approved by the U.S. Food and Drug Administration for the treatment of clinical depression. The treatment is also being studied as a potential therapy for Alzheimer’s disease.

How rTMS works

Alzheimer’s disease is the most common cause of dementia, affecting millions of mostly elderly people around the world. In these people, the synaptic activity (connections between nerve cells) collapses and brain networks gradually falter, resulting in a decline in memory and the ability to think and learn.

rTMS is a procedure that stimulates and modulates the nervous system. Doctors place a device on the patient’s scalp that sends electromagnet impulses to a specific area of the brain.

Although exactly how the technique works is unknown, researchers think the magnetic fields produce electric currents within the brain that influence the activity of nerve cells, stimulating them and helping improve the symptoms of Alzheimer’s disease.

rTMS in clinical trials

The effectiveness of targeted rTMS on expressive language was assessed in a clinical trial (NCT00814697) in 10 patients with Alzheimer’s disease.

The participants were randomly assigned to one of two groups. One group received rTMS treatment and the other received placebo. Trial results published in the Journal of Neurology, Neurosurgery, and Psychiatry, showed that the treatment arm presented significant improvements in correct responses in the comprehension of spoken sentences compared to placebo or prior to treatment.

A proof-of-concept study (NCT01504958) was also conducted to verify the effects of combined daily rTMS and cognitive training (tasks prepared by neuro-psychologists to target specific brain areas) in eight Alzheimer’s disease patients.

Trial results were published in the Journal of Neural Transmission and showed that rTMS led to an improvement in thinking abilities, measured by the ADAS-cog scores, a test used to measure the cognitive abilities of Alzheimer’s disease patients.

The same researchers conducted a randomized Phase 1 study (NCT01168245) to explore the long-term improvement in overall thinking ability in 15 Alzheimer’s patients after rTMS and cognitive training. They verified that the treatment significantly improved the ADAS-cog scores of the patients compared to the placebo group. The results were published in the Journal of Neural Transmission.

The potential of rTMS was also evaluated as a treatment for Alzheimer’s disease and to improve sleep quality in a pilot study (NCT01894620) in two stages.

Stage one was a double-blind crossover study with real and sham treatments of 13 sessions over four weeks; stage two was an open-label study where the same treatments were administered in 10 sessions as follow-up treatments.

Results of the study showed a stronger improvement on all assessments, including Montreal Cognitive Assessment (MOCA) scores, a brief 30-question test used to detect cognitive impairment and ADAS-cog scores. The findings were published in the Journal of Experimental Neuroscience.

Additionally, the potential effect of rTMS in enhancing apathy and working memory in Alzheimer’s patients is being evaluated in two trials. Apathy is defined as lack of interest, enthusiasm, or concern.

The first is a Phase 4 trial (NCT02190084) to determine the effectiveness of rTMS in treating apathy in Alzheimer’s compared to sham treatment. The primary outcome of the study is the apathy evaluation scale (AES), a test to assesses apathy in behavioral, cognitive, and emotional domains.

Secondary outcomes include tests to assess executive function, or the ability to plan, organize, and complete tasks. The trial, which aims to enroll up to 20 participants in the U.S., is expected to end by May 2018.

The second trial (NCT02537496) is aimed at assessing and enhancing working memory in patients with mild Alzheimer’s disease using rTMS. First, investigators will measure baseline neuroplasticity — the ability of the brain to change according to experience — and then use a four-week course of rTMS to enhance cognitive function.

Clinical and cognitive assessments will be performed one week, one month, and six months after rTMS treatment. Healthy volunteers will also be enrolled to carry out baseline cognitive assessments and a baseline measurement of neuroplasticity.

The trial, which is expected to be finished by August 2018, is recruiting up to 36 participants in Canada.

More information about each trial is available by clicking on its identification (NCT) number.