A novel TMS technique may prevent cognitive decline in Alzheimer's patients: Study

ITALY: According to new research that was just published in the journal Brain, repetitive transcranial magnetic stimulation (rTMS) that targets the precuneus seems to slow the progression of cognitive and functional deterioration in people with Alzheimer's disease (AD).

For AD patients, rTMS has been compared with sham therapy in a number of small, randomized controlled trials. rTMS considerably improved cognition in AD patients, according to a meta-analysis of these studies published in 2018, although there were no differences between the two groups' functional performance.

In order to treat AD, Emiliano Santarnecchi, PhD, the study's lead investigator, said that "our electromagnetic treatment method is unique in that it predominantly intervenes in the electrical rather than the chemical side of the brain."

50 AD patients from the Santa Lucia Foundation Hospital in Rome, Italy, participated in the ongoing phase 2 research under the direction of lead researcher Giacomo Koch, MD, PhD, between February 2018 and April 2020.

Patients who met certain score requirements on the Clinical Dementia Rating Scale and the Mini-Mental State Examination, had a confirmed diagnosis of mild to moderate AD, and exhibited CSF biomarker evidence of tau and amyloid pathology were eligible for the trial.

For two weeks, participants were given five times per week of either rTMS or sham treatment over the precuneus region of the brain. This was followed by a 22-week maintenance phase during which TMS was administered to all patients once per week. Researchers supplemented normal therapy with acetylcholinesterase inhibitors with rTMS (or a sham procedure), measuring cortical brain activity using an EEG throughout each treatment. At baseline, 12 weeks, and 24 weeks, patients were evaluated using a variety of cognitive and functional scales by researchers who were blinded to the study group.

Key findings of the trial:

• At 24 weeks, those who received rTMS kept their CDR-SB score consistent whereas those who received sham TMS saw their scores drop.
• In comparison to individuals who got the sham treatment, the TMS therapy significantly delayed cognitive decline during the duration of the experiment by 82%.
• those who received TMS performed better functionally.
• When compared to those who received sham treatment, those who received TMS demonstrated improved cognitive function on the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale.
• With an estimated mean change in ADAS-Cog score of -0.67 for the treatment group and -4.2 for the sham group, those who received TMS also showed improvement over the course of the research on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Mini-Mental State Examination (MMSE), illustrating a slowing of functional decline.
• For the treatment group and the sham group, the estimated mean change in MMSE score was 0.30 and 1.8, respectively.

The investigators claimed that the findings "provide for a therapeutic strategy that is noninvasive, demonstrably safe, precision-based, and it has the possibility of customizing to each patient through an innovative technique."

The US Food and Drug Administration (FDA) should approve the novel application for use in AD patients, subject to replication of the results in a larger sample, the researchers anticipate.

REFERENCE

Giacomo Koch, Elias Paolo Casula, Sonia Bonnì, Ilaria Borghi, Martina Assogna, Marilena Minei, Maria Concetta Pellicciari, Caterina Motta, Alessia D'Acunto, Francesco Porrazzini, Michele Maiella, Clarissa Ferrari, Carlo Caltagirone, Emiliano Santarnecchi, Marco Bozzali, Alessandro Martorana, Precuneus magnetic stimulation for Alzheimer's disease: a randomized, sham-controlled trial, Brain, 2022;, awac285, https://doi.org/10.1093/brain/awac285