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Objective: To explore the mechanism of olfactory three needle therapy on Parkinson's disease dementia (PDD) by observing its effects on expression of apolipoprotein E (ApoE)、glial fibrillary acidic protein (GFAP) and related core pathology substrates in the hippocampus of PDD model mice. Method: Male C57BL/6 mice were randomly divided into four groups: control group (Control), sham operation group (Sham), model group (Model) and acupuncture electrotherapy group (AE), with 10 mice in each group. The PD model was established by injecting 6-OHDA into the medial forebrain tract (MFB) and PDD mice were selected. After successful modeling and selection, the AE group received "olfactory three needle" electroacupuncture treatment. After 14 days of intervention, Morris water maze test and shuttle box test were used to evaluate the learning and memory ability of mice in each group. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of hippocampal CA1 region. Western blotting was used to detect the expression of αsyn, Aβ and ApoE proteins in hippocampal CA1 region. The colocation rate of ApoE and GFAP in hippocampal CA1 region was observed by double immunofluorescence markers. Result: Compared with Model group, the AE group exhibited a shortened escape latency in water maze (P< 0.01), increased platform crossing (P<0.05), increased active escape times of shuttle box (P<0.05), and reduced the average total time of electric stimulation (P<0.01). In the Model group, the neurons in the hippocampal CA1 area were sparsely arranged and showed signs of degeneration and necrosis; and cell nuclei were small, hyperchromatic and had unclear structures, indicating the appearance of nuclear pyrosis. In contrast, the AE group showed significant improvements in neuronal pathology, with most cells regularly arranged, round and large nuclei, lightly stained and clearly shaped. Compared with the Model group, the expression levels of αsyn, Aβ, ApoE protein and the colocalization rate of ApoE and GFAP in hippocampal CA1 region in AE group were decreased (P<0.01, P<0.01, P<0.01, P<0.05). Conclusion: The "Olfactory three needle" acupuncture can improve the cognitive ability and restore the morphological structure and function of neurons in PDD mice. The mechanism may be related to the inhibition of ApoE expression in astrocytes and the reduction of α-syn and Aβ deposition in hippocampal CA1 region. [ABSTRACT FROM AUTHOR]