Predictive values of pre-treatment brain age models to rTMS effects in neurocognitive disorder with depression: Secondary analysis of a randomised sham-controlled clinical trial.

Introduction: One major challenge in developing personalised repetitive transcranial magnetic stimulation (rTMS) is that the treatment responses exhibited high inter-individual variations. Brain morphometry might contribute to these variations. This study sought to determine whether individual's brain morphometry could predict the rTMS responders and remitters.

Methods: This was a secondary analysis of data from a randomised clinical trial that included fifty-five patients over the age of 60 with both comorbid depression and neurocognitive disorder. Based on magnetic resonance imaging scans, estimated brain age was calculated with morphometric features using a support vector machine. Brain-predicted age difference (brain-PAD) was computed as the difference between brain age and chronological age.

Results: The rTMS responders and remitters had younger brain age. Every additional year of brain-PAD decreased the odds of relieving depressive symptoms by ∼25.7% in responders (Odd ratio [OR] = 0.743, p = .045) and by ∼39.5% in remitters (OR = 0.605, p = .022) in active rTMS group. Using brain-PAD score as a feature, responder-nonresponder classification accuracies of 85% (3^rd week) and 84% (12^th week), respectively were achieved.

Conclusion: In elderly patients, younger brain age appears to be associated with better treatment responses to active rTMS. Pre-treatment brain age models informed by morphometry might be used as an indicator to stratify suitable patients for rTMS treatment.

Trial registration: ClinicalTrials.gov Identifier: ChiCTR-IOR-16008191.