Electroacupuncture to improve post-stroke cognitive function and modulate cerebral iron deposition: a randomized controlled trial protocol using MRI

Ning Sun¹Fang Xie²Zhetao Wang³Liu YiWei¹Hui-Lin Yang¹Lei Chen¹Jing-Kang Lu¹Yi He¹Chengqi He¹Shaxin Liu^1*

• ¹Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital of Sichuan University, Chengdu, China
• ²Chengdu University of Chinese Medicine, Cheng Du, China
• ³Department of Radiology, West China Hospital of Sichuan University, Chengdu, China

Background: Post-stroke cognitive impairment (PSCI) is common and hampers rehabilitation. Dysregulated iron homeostasis and ferroptosis are implicated in PSCI, yet targeted treatments are lacking. Acupuncture may improve cognition, but its early-intervention efficacy and iron-related mechanisms remain unclear. Methods and analysis: This single-blind randomized controlled trial will enroll 72 patients with ischemic stroke-related cognitive impairment (IS-CI). Participants will be randomized 1:1 to electroacupuncture (EA) or sham electroacupuncture (sEA) in addition to standard pharmacotherapy and rehabilitation. Participants in the EA group will receive verum stimulation at Baihui (GV20), Sishencong (EX-HN1), Shenting (GV24), and bilateral Neiguan (PC6), along with five adjunct points—Hegu (LI4), Zusanli (ST36), Xuanzhong (GB39), Sanyinjiao (SP6), and Taichong (LR3)—on the affected side. The sEA group will receive sham acupuncture at non-acupoint, non-meridian locations situated 1–2 cun away from the true acupoints. Interventions are delivered 5 times weekly for 4 weeks (20 sessions, 30 minutes each). The primary outcome is change in Montreal Cognitive Assessment (MoCA) score from baseline to week 4. Secondary outcomes include Mini-Mental State Examination (MMSE), Modified Barthel Index (MBI), Hamilton Anxiety (HAMA) and Depression (HAMD) scales, Pittsburgh Sleep Quality Index (PSQI), and PSCI incidence at 3 months post-stroke (MoCA <26). A prespecified MRI substudy (n=30) will use 3.0 T quantitative susceptibility mapping (QSM) to quantify regional cerebral iron and explore associations between changes in susceptibility and cognitive measures. Participants and outcome assessors are blinded; allocation is concealed; analyses will follow prespecified statistical plans. Conclusion: This trial is designed to evaluate the effects of EA on cognitive function in patients with IS-CI and to explore whether changes in cognition are accompanied by changes in cerebral iron deposition measured by QSM. It aims to assess the feasibility 3 and preliminary effects of this intervention and to explore iron-related mechanisms in PSCI using an imaging approach.