# Repetitive transcranial magnetic stimulation across neurodegenerative diseases: a systematic review and dose-response meta-analysis

## TL;DR

This study reviews and analyzes how the number of rTMS pulses affects treatment outcomes in Parkinson’s and Alzheimer’s diseases, finding a bell-shaped curve relationship.

## Contribution

The paper introduces a dose-response meta-analysis of rTMS pulses for neurodegenerative diseases, revealing optimal pulse thresholds for efficacy.

## Key findings

- rTMS shows significant bell-shaped curves for motor and non-motor symptoms in Parkinson’s and Alzheimer’s diseases.
- Increasing rTMS pulses beyond a threshold reduces therapeutic efficacy for both conditions.
- Meta-analysis included 51 studies with 1,938 subjects, showing optimal pulse ranges for symptom improvement.

## Abstract

We summarized the existing clinical evidence of repetitive transcranial magnetic stimulation (rTMS) for Parkinson’s Disease (PD) and Alzheimer’s Disease (AD) and conducted a series of dose-response meta-analyses to determine the curve relationship between the number of pulses and the effect size of the treatment.

Existing evidence was retrieved from five databases, and relevant outcome data on rTMS treatment for motor and non-motor symptoms of PD and AD were collected. Data were analyzed using R software to assess effect size using standardized mean differences (SMD) and 95% confidence intervals (CI). Heterogeneity testing was performed to assess differences in efficacy among the evidence, and restricted cubic spline (RCS) was used to fit the dose-response curves.

A total of 51 publications were included, involving 1,938 subjects. We found that for PD patients, the total number of rTMS pulses showed significant bell-shaped curves in TUG (χ2 = 6.87, df = 2, p = 0.03), FOGQ (χ2 = 15.17, df = 2, p = 0.001), BDI (χ2 = 14.33, df = 2, p = 0.001), HAMD (χ2 = 12.63, df = 2, p = 0.001), and HAMA (χ2 = 6.06, df = 2, p = 0.04). For AD patients, the total number of rTMS pulses demonstrated significant bell-shaped curves for MMSE (χ2 = 8.76, df = 2, p = 0.01) and MoCA (χ2 = 6.79, df = 2, p = 0.03).

Our dose-response meta-analysis results show that rTMS demonstrates significant efficacy in certain motor and non-motor symptoms of PD and AD. The number of rTMS pulses presents a typical bell-shaped curve for these symptoms, indicating that more number of rTMS pulses is not always better; beyond a certain threshold, increasing the number of rTMS pulses correlates negatively with therapeutic efficacy.