Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by tremor, rigidity, bradykinesia and postural instability. A major complication is that mild cognitive impairment is commonly associated with PD and about 80% of patients will eventually develop dementia. Biomarkers are needed to follow and help predict the cognitive progression of PD for improved disease management and prognosis. It is suggested that saccades (rapid eye movements) may provide a direct measure of the oculomotor pathways and associated control systems that degenerate in PD and thus a possible biomarker for cognitive impairment in this disorder.In the first and major study, one hundred and one patients with PD and 47 healthy age and education matched controls were recruited. Comprehensive neuropsychological testing classified PD patients as either cognitively normal (PDN, n = 59), with mild cognitive impairment (PD-MCI n = 25), or with dementia (PDD, n = 17). Eye movements were recorded with a video-based iView X Hi-Speed tracking system. Each participant completed reflexive, predictive, self-paced, memory-guided and antisaccade oculomotor paradigms. In all tasks, PDD patients exhibited prolonged latency, reduced gain (accuracy) and increased errors relative to PD-MCI patients. PD-MCI patients in turn exhibited prolonged latency, reduced gain and increased errors relative to control and PDN groups, who did not differ. Regression analysis showed that cognitive status significantly influenced latency and primary gain in each saccadic task, percent of predictive saccades, percent of memory-guided errors and percent of antisaccade errors. These saccade measures all highly correlated with cognitive status even after controlling for motor function, age, education and sex.Study 2 examined whether saccades could be used to assess changes in cognitive function resulting from amantadine or anticholinergic treatment. Study 2 used the same paradigms as in study 1, in a pre-post treatment design, using recently (less than five years) diagnosed patients (n=36) without cognitive impairment initiated on either amantadine (n=22) or anticholinergic (n=14) treatment as their first antiparkinson medication. Pre and post treatment test scores in these patients and a control (n=26) group were compared using ANOVA. Anticholinergic treatment reduced neuropsychological scores, and increased memory-guided errors. Amantadine treatment showed a small, but significant improvement in general cognitive performance and saccade primary gain in the predictive and self-paced tasks. In conclusion, a cross sectional study (Study 1), showed that a range of saccade measures was strongly associated with cognition in PD indicating that they may prove to be a unique biomarker of PD status and progression. Study 2 assessed the use of saccade measures to track cognitive changes associated with two drug treatments in early PD. In future a longitudinal study is desirable to determine whether saccadic parameters (including latency, accuracy and error rate) may faithfully reflect PD progression.
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Cognition and eye movements in Parkinson's disease