Short and Long-term Effects of rTMS Treatment on Alzheimer's Disease at Different Stages: A Pilot Study

Abstract

Repetitive transcranial magnetic stimulation (rTMS) uses a magnetic coil to induce an electric field in brain tissue. As a pilot study, we investigated the effect of rTMS treatment on 10 volunteers with Alzheimer's disease (AD) in a two-stage study. The first stage consisted of a double-blind crossover study with real and sham treatments. Each treatment block consisted of 13 sessions over 4 weeks. During each session, 2000 TMS pulses at 90%-100% of resting motor threshold were applied to dorsolateral prefrontal cortex bilaterally, and the patients were kept cognitively active by object/action naming during the treatment. The second stage was an open-label study, in which the same treatments were performed in 2-week blocks (10 sessions) approximately every 3 months as follow-up treatments on six of the volunteers, who completed the first stage of the study. Primary outcome measures were the Montreal Cognitive Assessment (MOCA) and the Alzheimer's Disease Assessment Scale-cognitive subscale. The secondary outcome measures were the Revised Memory and Behavior Checklist as well as our team's custom-designed cognitive assessments. The results showed a noticeably stronger improvement on all assessments during the real treatment as compared to the sham treatment. The changes in MOCA scores as well as our designed cognitive assessment were found to be statistically significant, with particularly strong results in the six volunteers who were in the early stages of the disease. The long-term trends observed in the second stage of the study also showed generally less decline than would be expected for their condition. It appears that rTMS can be an effective tool for improving the cognitive abilities of patients with early to moderate stages of AD. However, the positive effects of rTMS may persist for only up to a few weeks. Specific skills being practiced during rTMS treatment may retain their improvement for longer periods.

Keywords: ADAS-Cog; Alzheimer’s disease; MoCA; cognitive assessments; transcranial magnetic stimulation; treatment.

Figure 1

Illustration of the timing of images presented to the patients.

Figure 2

Change in MOCA scores averaged among the patients. The dotted and dashed lines show the scores of real and sham treatments, respectively. The bars show standard errors. Stars indicate significant differences using paired t-tests.

Figure 3

Baseline ADAS-cog scores. Two distinct levels of ability were identified in our patients: Six “early stage” patients and four “advanced stage” patients. “Early stage” patients performed significantly better on the ADAS-cog assessment at baseline.

Figure 4

Change in MOCA scores averaged among the “early stage” patients (six patients). The dotted and dashed lines show the scores of real and sham treatments, respectively. The bars show standard errors. Stars indicate significant differences using paired t-tests.