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Autonomic dysfunction is increasingly recognized in Alzheimer’s disease (AD). We evaluated whether ultrasound guided stellate ganglion block(SGB) as an adjunct to standard drug therapy was associated with better outcomes in patients with clinically diagnosed mild to moderate Alzheimer’s disease(AD). We conducted a prospective, single center, assessor blinded, parallel group randomized trial. Forty patients aged 55 to 85 years with clinically diagnosed mild to moderate Alzheimer’s disease (AD) were randomized 1:1 to stellate ganglion block(SGB) plus standard drug therapy or standard drug therapy alone. The intervention included 10 ultrasound guided sessions over about 20 days, with alternating sides. Outcomes were assessed at baseline, day 20 after treatment, and at 1, 3, and 6 months. The prespecified outcome was global cognition measured by the Mini-Mental State Examination(MMSE) at 1 month. Secondary outcomes included depression, anxiety, quality of life, and instrumental activities of daily living. Efficacy was analyzed in the intention to treat population using longitudinal linear mixed effects models. Adverse events were monitored throughout the study. All 40 randomized participants were included in the intention to treat analysis. At one month, Mini-Mental State Examination (MMSE) was higher in the intervention group, with a between group difference of 4.51 points (95% CI 1.94 to 7.08). Differences also favored the intervention group at day 20, 3 months, and 6 months. At 1 month, depression and anxiety scores were lower, with between group differences of -7.14 (95% CI -12.48 to -1.80) and -11.56 (95% CI -18.08 to -5.04). Quality of life and instrumental activities of daily living were higher, with between group differences of 7.62 (95% CI 4.93 to 10.31) and 3.00 (95% CI 0.29 to 5.71). No serious adverse events occurred. In the intervention group, 4 of 20 participants reported mild transient adverse events that resolved within 30 min. No adverse events were reported in the control group. In this exploratory assessor blinded trial, ultrasound guided stellate ganglion block (SGB) as an adjunct to standard drug therapy was associated with higher cognitive scores and exploratory signals in several nonprimary domains in patients with clinically diagnosed mild to moderate Alzheimer’s disease (AD). These findings should be interpreted with caution, particularly because biomarker confirmation was not available. Larger sham controlled trials in more rigorously characterized populations are needed to determine whether these preliminary signals reflect a true treatment effect and to define the optimal treatment schedule. Trial registration ClinicalTrials.gov identifier: NCT07351773, retrospectively registered on 30 December 2025. National Medical Research Registration and Record System (China): MR-33–25-088660.