Prolonged visual fixation as a surrogate marker of cholinergic deficit in Parkinson's disease: A 2-year follow-up study.

INTRODUCTION: The search for biomarkers of cognitive impairment in Parkinson's disease is driven by the potential clinical applications in disease prognostication. Various eye tracking studies on cognitive functions in Parkinson's disease suggest a promising role of eye movement parameters as a biomarker for cognitive decline but the clinical utility has not been validated in longitudinal studies. The present study aims to investigate the longitudinal progression of eye fixation duration in a visual search task and its correlation with domain-specific cognitive impairment. METHOD: This is a 2-year follow-up study on a group of non-demented Parkinson's disease patients, with baseline eye movement metrics and multi-domain cognitive functions measured, to assess the association between domain-specific cognitive impairment and progression of visual fixation duration. RESULTS: A total of 49 from the original 62 non-demented Parkinson's disease patients were re-examined at a 2-year follow-up. 15 cases (31%) were classified as having mild cognitive impairment. Visual fixation duration was significantly prolonged after 2 years. Using repeated measures ANOVA, impairment in semantic verbal fluency, visual and verbal recognition memory and orienting function of attention had a significant effect on prolonging visual fixation over time. CONCLUSION: Correlation between prolonged visual fixation and multiple domains of cognitive impairment related to cholinergic dysfunction in repeated measures over two years provides preliminary evidence for the eye tracking paradigm as a surrogate marker for cholinergic deficit in Parkinson's disease. The clinical utility in terms of disease prognostication is yet to be confirmed in prospective longitudinal studies with longer follow-up periods.

Eye movement parameters and cognitive functions in Parkinson's disease patients without dementia.

BACKGROUND: Cognitive deficits and eye movement abnormalities have been demonstrated to be detectable early clinical manifestations of Parkinson's disease. Understanding the relationship between these phenotypes may yield insight into the underlying anatomical pathways, assisting in the search for simple non-invasive markers of early neurodegeneration. OBJECTIVE: To explore the correlations between eye movement parameters with multi-domain cognitive functions in patients suffering from Parkinson's disease without dementia. METHOD: This is a cross-sectional case-control study of Parkinson's disease patients without dementia. Participants underwent global and domain-specific cognitive tests and an eye-tracking visual search task to characterize eye movement parameters. RESULTS: 62 Chinese Parkinson's disease patients without dementia and 62 sex-, age- and education-matched controls were recruited. The disease group performed worse in multiple cognitive tasks and exhibited a smaller saccadic amplitude. Negative correlations between the eye fixation duration and performance in semantic verbal fluency, verbal and visual recognition memory tasks were observed, though there was no moderation effect on the correlations due to the presence of Parkinson's disease. A common cholinergic deficit in the temporal and parietal regions may account for the observed correlations. The lack of association with predominantly frontal-executive tasks may suggest specificity of these correlations. CONCLUSION: Prolonged visual fixation duration is correlated with poorer performance in semantic verbal fluency, verbal and visual recognition memory tasks in Parkinson's disease patients without dementia, although these correlations are not specific. The clinical utility of eye movement parameters as an early marker for cognitive decline in Parkinson's disease warrants further exploration in longitudinal studies.