Can Brain Volume-Driven Characteristic Features Predict the Response of Alzheimer's Patients to Repetitive Transcranial Magnetic Stimulation? A Pilot Study

Abstract

This study is a post-hoc examination of baseline MRI data from a clinical trial investigating the efficacy of repetitive transcranial magnetic stimulation (rTMS) as a treatment for patients with mild-moderate Alzheimer's disease (AD). Herein, we investigated whether the analysis of baseline MRI data could predict the response of patients to rTMS treatment. Whole-brain T1-weighted MRI scans of 75 participants collected at baseline were analyzed. The analyses were run on the gray matter (GM) and white matter (WM) of the left and right dorsolateral prefrontal cortex (DLPFC), as that was the rTMS application site. The primary outcome measure was the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog). The response to treatment was determined based on ADAS-Cog scores and secondary outcome measures. The analysis of covariance showed that responders to active treatment had a significantly lower baseline GM volume in the right DLPFC and a higher GM asymmetry index in the DLPFC region compared to those in non-responders. Logistic regression with a repeated five-fold cross-validated analysis using the MRI-driven features of the initial 75 participants provided a mean accuracy of 0.69 and an area under the receiver operating characteristic curve of 0.74 for separating responders and non-responders. The results suggest that GM volume or asymmetry in the target area of active rTMS treatment (DLPFC region in this study) may be a weak predictor of rTMS treatment efficacy. These results need more data to draw more robust conclusions.

Keywords: Alzheimer’s disease (AD); DLPFC; MRI analysis; efficacy prediction; rTMS treatment.

Figure 1

The left (red) and right (blue) dorsolateral prefrontal cortex (DLPFC) masks are shown on the modulated and warped (a) gray matter and (b) white matter images (axial view) of a participant.

Figure 2

Comparison of normalized (a) gray matter (GM) or (b) white matter (WM) volumes (mean ± SE) between left DLPFC and right DLPFC for responders and non-responders under active treatment. Normalized volume is calculated by dividing each region’s raw volume of GM or WM by the total intracranial volume (TIV). Results of the two-tailed paired t-test are shown (**** p ≤ 0.0001, ** p ≤ 0.01, and ns: p > 0.05).

Figure 3

Scatter plots of baseline ADAS-Cog scores of responders and non-responders under active treatment and their raw GM volumes (cm³) of (a) left and (b) right dorsolateral prefrontal cortex (DLPFC).