# Effect of perioperative repetitive transcranial magnetic stimulation on postoperative cognitive function and peripheral inflammation in elderly total knee arthroplasty patients: study protocol for a randomized controlled trial

## TL;DR

This study tests if rTMS can reduce post-surgery cognitive issues and inflammation in elderly knee replacement patients.

## Contribution

This is the first trial to investigate perioperative rTMS as a preventive intervention for postoperative cognitive dysfunction in TKA patients.

## Key findings

- rTMS may reduce neuroinflammation and cognitive decline by targeting the DLPFC pre-surgery.
- The trial will assess changes in cognitive scores and inflammatory markers like IL-1β, IL-6, and TNF-α.
- Results could clarify if rTMS provides neuroprotection by blocking POCD pathways.

## Abstract

Postoperative cognitive dysfunction (POCD) is a serious and common complication after total knee arthroplasty (TKA) in the elderly. Studies have suggested that repetitive transcranial magnetic stimulation (rTMS) can reduce the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) inflammatory factors in the hippocampus, inhibit neuroinflammatory responses in the brain, and reduce the damage to synapses, thereby improving cognitive dysfunction. However, the effectiveness of rTMS for POCD remains to be explored. Therefore, the aim of this study is to treat POCD after TKA in the elderly with rTMS to evaluate the clinical efficacy of rTMS for POCD.

This single-center, randomized, sham-controlled, assessor-blinded, parallel-group trial will enroll 207 elderly patients undergoing TKA and allocate them 1:1:1 to control group, active rTMS group, or sham rTMS group. All participants will receive standardized perioperative management. In addition, patients randomized to the active rTMS group will undergo stimulation of the left dorsolateral prefrontal cortex (DLPFC) at 10 Hz, 2000 pulses per session (5 s trains with 25 s inter-train intervals; 100% resting motor threshold), once daily for five consecutive pre-operative days. The sham rTMS group will follow the identical target and schedule, but the coil will be oriented perpendicular to the skull to avoid effective cortical stimulation. Primary outcome includes incidence of POCD at postoperative day seven (MoCA-based item-level definition). Secondary outcomes include changes in the MoCA total score and a prespecified cognitive subtest battery comprising the Digit Span Test (DST), Digit Symbol Substitution Test (DSST), Trail Making Test (TMT), and Delayed Story Recall (DSR), together with changes in serum inflammatory markers (IL-1β, IL-6, TNF-α, and HMGB1), assessed at preoperative day six, preoperative day one, postoperative day three, and postoperative day seven.

This trial will contribute to addressing the effectiveness of perioperative rTMS stimulation in elderly patients with TKA, and will initially clarify that perioperative rTMS preventive intervention can produce neuroprotective effects to reduce oxidative stress and inflammation, and to some extent block the possible pathway of POCD occurrence, thereby reducing the risk of POCD occurrence.

ClinicalTrials.gov ChiCTR2400081372. Registered on 29 February 2024.

The online version contains supplementary material available at 10.1186/s13063-025-09158-1.