Efficacy and safety of infra-low-frequency transcranial magnetic stimulation in Alzheimer's disease patients with behavioral and psychological symptoms of dementia: study protocol for a randomized parallel-design controlled trial

Background and objectives: Patients with Alzheimer's disease (AD) often experience abnormal mental and behavioral symptoms. Clinically, antipsychotic and antidepressant drugs are often used to control behavioral and psychological symptoms of dementia (BPSD), but these drugs have anticholinergic and vertebral effects and have the risk of affecting metabolic diseases and increasing stroke mortality. Infra-low-frequency transcranial magnetic stimulation (ILF-TMS) can regulate the electrical activity of each transmitter, modulating the physiological function of the transmitter to achieve therapeutic effects. Thus, this randomized parallel-design controlled trial examined the use of ILF-TMS as a treatment for BPSD in patients with AD. The study aims to evaluate the efficacy and safety of ILF-TMS in patients with AD who also show BPSD following conventional drug therapy. Design: This is a randomized parallel-design controlled trial. Methods: AD patients with BPSD in the Beijing Geriatric Hospital, China will be randomized into control (sham stimulation) and stimulation groups (n = 50/group). Eight patients from each group will participate in a preliminary experiment, and the remaining 42 will participate in the trial. For the stimulation group, along with conventional drug therapy, participants will be exposed to ILF-TMS (stimulation frequency < 0.2 Hz; total magnetic field strength, 0.1–40 mT) for 20 minutes per exposure 5 times/week for 8 consecutive weeks. Patients in the control group will undergo sham stimulation and conventional drug therapy. Outcome measures: The primary outcome measure will be neuropsychiatric inventory score differences observed before treatment, at 4 and 8 weeks of treatment, and 4 weeks after treatment. The secondary outcome measures will be Mini-Mental State Examination and Barthel Index scores before treatment, at 4 and 8 weeks of treatment, and 4 weeks after treatment. Discussion: The trial is intended to explore a potential new approach for the treatment of behavioral and psychiatric symptoms in patients with AD. This will help to improve poor mental symptoms and the quality of life and reduce psychological and social burdens. Ethics and dissemination: The protocols have been approved by the ethics committee of Beijing Geriatric Hospital of China (approval No. 2016-021) on November 11th, 2016. Study design completed October 2016; ethical approval received November 2016; clinical registration conducted January 2017; patient recruitment began January 2017. Each patient will receive 8 weeks of treatment and 4 weeks of follow-up. Follow-up will be completed December 2017, and data analysis will be completed December 2018. Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals. Trial registration: This trial has been registered in the Chinese Clinical Trial Registry (registration No. ChiCTR-INR-17010487) on January 20th, 2017.