Multiple step saccades in simply reactive saccades could serve as a complementary biomarker for the early diagnosis of Parkinson’s disease

Abstract

Objective: It has been argued that the incidence of multiple step saccades (MSS) in voluntary saccades could serve as a complementary biomarker for diagnosing Parkinson’s disease (PD). However, voluntary saccadic tasks are usually difficult for elderly subjects to complete. Therefore, task difficulties restrict the application of MSS measurements for the diagnosis of PD. The primary objective of the present study is to assess whether the incidence of MSS in simply reactive saccades could serve as a complementary biomarker for the early diagnosis of PD. Materials and methods: There were four groups of human subjects: PD patients, mild cognitive impairment (MCI) patients, elderly healthy controls (EHCs), and young healthy controls (YHCs). There were four monkeys with subclinical hemi-PD induced by injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) through the unilateral internal carotid artery and three healthy control monkeys. The behavioral task was a visually guided reactive saccade. Results: In a human study, the incidence of MSS was significantly higher in PD than in YHC, EHC, and MCI groups. In addition, receiver operating characteristic (ROC) analysis could discriminate PD from the EHC and MCI groups, with areas under the ROC curve (AUCs) of 0.76 and 0.69, respectively. In a monkey study, while typical PD symptoms were absent, subclinical hemi-PD monkeys showed a significantly higher incidence of MSS than control monkeys when the dose of MPTP was greater than 0.4 mg/kg. Conclusion: The incidence of MSS in simply reactive saccades could be a complementary biomarker for the early diagnosis of PD.