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. 2025 Mar 25:20:26331055251328355.
doi: 10.1177/26331055251328355. eCollection 2025.

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

Brian J Lithgow  1   2   3 , Chandan Saha  1 , Zeinab Dastgheib  1 , Zahra Moussavi  1   3
Affiliations

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

Brian J Lithgow et al. Neurosci Insights. .

Abstract

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.

Keywords: ADAScog; Alzheimer’s Disease; cerebrovascular disease; rTMS.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
For HIS = 4 threshold estimated marginal means of ADAScog score change versus time. (Time 1, 2, 3, 4 = W5, W12, W20, W28).
Figure 2.
Figure 2.
For HIS = 2 threshold estimated marginal means of ADAS-Cog score change versus time. (Time 1, 2, 3, 4 = W5, W12, W20, W28).
Figure 3.
Figure 3.
For HIS = 4 threshold estimated marginal means of ADAS-Cog changes versus time. (Time 1, 2 = W5, W12).
Figure 4.
Figure 4.
For HIS = 2 threshold estimated marginal means of ADAS-Cog changes versus time. (Time 1, 2 = W5, W12).
See this image and copyright information in PMC

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