Surface Versus Penetrative rTMS Stimulation May Be More Effective for AD Patients with Cerebrovascular Disease

Repetitive Transcranial Magnetic Stimulation (rTMS) has been applied as an investigational therapy for Alzheimer's Disease (AD). The recent largest (N = 135) double-blind study with 6 months post-treatment follow-up investigating rTMS efficacy as a treatment for AD found about 72% of participants in each group of active and sham were positively responsive to rTMS (using Magstim AirFilm active and sham coils). Since the used sham coil produced about 25.3% of the peak active stimulus, it was hypothesized it could evoke a measurable response in AD patients. This study looks at the details of the above study's sham responses to determine why and how such a response might occur and how cerebrovascular symptomatology may have impacted that response. In the above-mentioned study, 90 and 45 patients were randomly assigned to active and sham groups, respectively. Those with modified Hachinski Ischemic Scores (HIS) below and above 2 were labeled AD₂ and ADcvd₂, respectively. Analysis of the primary outcome measure ADAS-Cog score change from baseline to post-treatment and follow-ups showed the ADcvd₂ in the sham group had a significantly (p = .034) greater improvement or less decline at post-treatment and follow-up sessions compared to the ADcvd₂ in the active group. Additionally, the improvement of the ADcvd₂ sham compared to those in the active group persisted longer. Also, there was a significant (p = .036) improvement for AD₂ individuals in the active compared to AD₂ sham stimulation group at 2-months post-treatment. Overall, the sham rTMS stimulus did evoke a measurable response which was more effective for ADcvd₂ in sham than ADcvd₂ in active support of a vascular mechanism likely linked to the shallower sham stimulus penetration.