Efficacy and acupoint specificity of sedative-tranquilizing acupuncture for Alzheimer’s disease with sleep disorders: a three-arm randomized controlled trial protocol

Sleep disorders (SD) are highly prevalent in patients with Alzheimer's disease (AD); however, effective pharmacological interventions are often limited by adverse effects or insufficient efficacy. This study aims to evaluate the clinical synergistic value and the “sleep-cognition co-modulation” effect of sedative-tranquilizing acupuncture, a specialized non-pharmacological therapy, in managing AD-SD comorbidity. This is a multicenter, randomized, controlled trial (RCT) involving 72 participants diagnosed with both AD and SD. Participants will be randomly assigned (1:1:1) to one of three groups: the control group, receiving standard care (donepezil hydrochloride combined with cognitive behavioral therapy for insomnia [CBT-I]); the acupuncture group, receiving sedative-tranquilizing acupuncture in addition to standard care; and the sham acupuncture group, receiving sham acupuncture plus standard care. The primary outcome measure is the change from baseline in the Pittsburgh Sleep Quality Index (PSQI) score. Secondary outcomes include cognitive function (Mini-Mental State Examination [MMSE]), quality of life (Quality of Life in Alzheimer’s Disease [AD-QOL] scale), and psychological symptoms (Hamilton Anxiety Scale [HAMA] and the 17-item Hamilton Depression Scale [HAMD-17]). Furthermore, peripheral biochemical markers, polysomnography (PSG) parameters, and neuroimaging data will be analyzed to explore underlying mechanisms. All analyses will be performed on an intention-to-treat (ITT) basis. This trial is expected to provide robust clinical evidence regarding whether sedative-tranquilizing acupuncture can effectively assist in improving sleep quality and cognitive function in patients with AD-SD comorbidity. The findings will further elucidate the potential neurobiological mechanisms of acupuncture and offer a novel integrative strategy for the management of AD-related sleep disturbances. This protocol was approved by the Ethics Committee of Nanchang Hongdu Hospital of Traditional Chinese Medicine (KYKS-2024044-1(X-2) and registered with the International Traditional Medicine Clinical Trial Registry ( https://itmctr.ccebtcm.org.cn/mgt/project/user/user-project-view/09DB9DBC-F576-4AF9-AF4E-D6D88E1B1B6B ) • The first RCT to investigate the “Sedative-tranquilizing acupuncture” acupuncture protocol specifically for AD-SD comorbidity. • The rigorous three-arm design, including control, acupuncture, and sham acupuncture groups, effectively distinguishes specific acupuncture effects from non-specific placebo responses and standard treatments. • Sleep-cognition co-modulation is driven by synergistic multimodal signatures identifiable via EEG, fMRI, and plasma biomarkers. • Findings support acupuncture as a safe, non-pharmacological complementary therapy for AD-SD comorbidity.