ObjectivesThe study aimed to analyze the clinical features and gait characteristics of patients with Parkinson's disease (PD) who also suffer from fatigue and to develop a model that can help identify fatigue states in the early stages of PD.MethodologyA total of 81 PD patients have been enrolled for the Parkinson's Fatigue Scale (PFS-16) assessment and divided into two groups: patients with or without fatigue. Neuropsychological assessments of the two groups, including motor and non-motor symptoms, were collected. The patient's gait characteristics were collected using a wearable inertial sensor device.ResultsPD patients who experienced fatigue had a more significant impairment of motor symptoms than those who did not, and the experience of fatigue became more pronounced as the disease progressed. Patients with fatigue had more significant mood disorders and sleep disturbances, which can lead to a poorer quality of life. PD patients with fatigue had shorter step lengths, lower velocity, and stride length and increased stride length variability. As for kinematic parameters, PD patients with fatigue had lower shank-forward swing max, trunk-max sagittal angular velocity, and lumbar-max coronal angular velocity than PD patients without fatigue. The binary logistic analysis found that Movement Disorder Society-Unified Parkinson's Disease Rating Scale-I (MDS-UPDRS-I) scores, Hamilton Depression Scale (HAMD) scores, and stride length variability independently predicted fatigue in PD patients. The area under the curve (AUC) of these selected factors in the receiver operating characteristic (ROC) analysis was 0.900. Moreover, HAMD might completely mediate the association between Hamilton Anxiety Scale (HAMA) scores and fatigue (indirect effect: β = 0.032, 95% confidence interval: 0.001–0.062), with a percentage of mediation of 55.46%.ConclusionCombining clinical characteristics and gait cycle parameters, including MDS-UPDRS-I scores, HAMD scores, and stride length variability, can identify PD patients with a high fatigue risk.