# Quantitative Electroencephalographic Biomarkers for Repetitive Transcranial Magnetic Stimulation Treatment Response Prediction in Mild Cognitive Impairment: A Pilot Study Protocol for Multi‐Center, Assessor‐Blinded, Open‐Label Clinical Trial

## TL;DR

This study aims to find EEG patterns that predict which patients with mild cognitive impairment will benefit from brain stimulation therapy.

## Contribution

The study introduces a novel approach using baseline QEEG features to predict rTMS treatment response in MCI patients.

## Key findings

- Baseline QEEG features will be compared between responders and non-responders to identify predictive biomarkers.
- The trial will assess if pre-treatment EEG data can optimize rTMS use in MCI patients.
- Cognitive improvements will be measured using MMSE and MoCA to classify treatment response.

## Abstract

Over 55 million people worldwide suffer from dementia, with 10 million new cases diagnosed annually. Due to the limited efficacy of drug therapies, alternative approaches like repetitive transcranial magnetic stimulation (rTMS) have gained popularity as a non‐invasive, safe method leveraging neural plasticity and brain connectivity. However, its high cost and time commitment highlight the need for biomarkers to predict treatment response.

This pilot study aims to identify a quantitative electroencephalography (QEEG) biomarker to predict which mild cognitive impairment patients will respond to rTMS. By targeting responders early, clinicians can make rTMS more cost‐effective and time‐efficient, reducing wasted treatment on non‐responders.

This multi‐center, assessor‐blinded clinical trial will examine QEEG biomarkers as predictors of rTMS treatment responsiveness in 25 patients with mild cognitive impairment (MCI). Adults aged 60 years or older will undergo cognitive assessments using the Montreal Cognitive Assessment (MoCA) or mini‐mental state examination (MMSE) and have an electroencephalography (EEG) recording. Participants will complete 10 rTMS sessions targeting the left DLPFC over 2 weeks, with 2000 pulses per session at 20 Hz. Cognitive tests will be repeated post‐treatment, and participants will be classified as responders or non‐responders based on cognitive changes, then baseline QEEG parameters will be compared between the two groups. The primary endpoint is the proportion of responders at ten sessions after rTMS (score post‐intervention > score pre‐intervention = responder, according to the minimal clinically important difference (MCID) threshold (i.e., an increase of at least 3 points or 10% on the MMSE, or an increase of at least 1 point on the MoCA); score post‐intervention ≤ score pre‐intervention = non‐responder). The secondary endpoints are the differences in baseline QEEG features between responders and non‐responders.

By identifying responders prior to treatment, we can optimize resource allocation, minimize the time and cost associated with ineffective treatments, and ultimately improve the quality of care for individuals with MCI.

IRCT registration number: IRCT20240218061042N1 (version updated September 7, 2024)

Repetitive transcranial magnetic stimulation (rTMS) enhances neural plasticity in mild cognitive impairment (MCI), but treatment success varies across individuals. In this pilot multicenter trial, quantitative EEG (QEEG) signals recorded before therapy are analyzed to identify predictors of clinical response. Patients receive 10 sessions of high‐frequency rTMS over the left DLPFC, and are classified as responders or non‐responders based on cognitive improvement. Baseline QEEG features distinguishing responders can serve as non‐invasive biomarkers to optimize rTMS resource allocation and personalize dementia care.