Abstract： Objective： To observe the effect of the therapy of Qingxin Kaiqiao Prescription combined with Donepezil Hydrochloride Tablets on the cognitive function，traditional Chinese medicine （TCM） syndromes and nerve damage indexes of patients with early-onset Alzheimer's Disease （AD） of orifices confused by phlegm type. Methods： A total of 104 patients with early-onset AD of orifices confused by phlegm type admitted to Quzhou Hospital of Traditional Chinese Medicine from February 2023 to April 2024 were selected and divided into the combination group and the western medicine group according to the random number table method， with 52 cases in each group. The western medicine group was treated with Donepezil Hydrochloride Tablets，and the combination group was additionally treated with Qingxin Kaiqiao Prescription based on the treatment of the western medicine group. Both groups were treated for 12 weeks. The cognitive function indexes [scores of Alzheimer's Disease Assessment Scale Cognitive Subscale（ ADAS-cog） and Mini-Mental State Examination（ MMSE） scale]，TCM syndrome（ the head feels heavy as if wrapped, accompanied by obesity and abundant phlegm, a lack of desire and speech, depression and indifference, as well as frequent dreams and early waking） scores， nerve damage indexes [neuron-specific enolase （NSE） and calciumbinding protein B （S100B）]，clinical effects and incidence of adverse reactions were compared between the two groups. Results：After 12 weeks of treatment，the ADAS-cog scores，various TCM syndrome scores，and levels of NSE and S100B in the two groups were lower than those before treatment， and the ADAS-cog scores， various TCM syndrome scores，and levels of NSE and S100B in the combination group were lower than those in the western medicine group， differences being significant （P＜0.05）. The MMSE scores in the two groups were higher than those before treatment， and the MMSE score in the combination group was higher than that in the western medicine group， differences being significant （P＜0.05）. The total effective rate was 89.80% （44/49） in the combination group， higher than that of 73.47% （36/49） in the western medicine group，the difference being significant （P＜0.05）. The incidence of adverse reactions was 12.24% （6/49） in the combination group and 8.16% （4/49） in the control group， there being no significance in the difference （P＞0.05）. Conclusion： Compared with the single use of Donepezil Hydrochloride Tablets， the combination use of Qingxin Kaiqiao Prescription and Donepezil Hydrochloride Tablets can enhance the clinical effect on early-onset AD of orifices confused by phlegm type， which can improve the cognitive function and reduce the nerve damage with great safety.