IntroductionAmnestic mild cognitive impairment (aMCI) is a high-risk precursor to Alzheimer's disease (AD). Acupuncture has been shown to improve cognitive function and regulate the brain function in patients with aMCI. Nevertheless, acupuncture's underlying cerebral mechanism in patients with aMCI is incompletely revealed. Therefore, this study proposes to investigate acupuncture's effect and cerebral mechanism for aMCI. MethodsThis study will be a randomized, parallel, and controlled trial. The trial will consist of a 12-week treatment period along with a 12-week follow-up period. The study will enrol 72 patients who have been diagnosed with aMCI. They will be randomly assigned to one of two groups, acupuncture and waiting list, in a 1:1 ratio. Each subject in either group will receive health education about improving cognitive function for 24 weeks. In addition, 20 healthy subjects will be included in the control group. The primary outcome will be an assessment of changes in global cognitive function that will be evaluated using Alzheimer's Disease Assessment Scale-Cognitive at baseline to 12 and 24 weeks after randomization. Acupuncture's neuroimaging mechanism will be investigated by detecting changes in cerebral functional connectivity at baseline and treatment endpoint. Furthermore, the imaging data will be correlated with clinical variables to investigate the possible relationship between acupuncture effect and functional connectivity. ConclusionThis study is envisaged to provide high-quality evidence from a clinical randomized controlled trial of the effect of acupuncture on the treatment of aMCI. Meanwhile, our results will partially illuminate the neuroimaging mechanism to understand how acupuncture exerts its effective role. Trial registrationChinese Clinical Trials Register ChiCTR2200062062.