Frontal functional connectivity and disease duration interactively predict cognitive decline in Parkinson's disease

Abstract Objective Cognitive decline does not always follow a predictable course in Parkinson’s disease (PD), with some patients remaining stable while others meet criteria for dementia from early stages. Functional connectivity has been proposed as a good correlate of cognitive decline in PD, although it has not been explored whether the association between this connectivity and cognitive ability is influenced by disease duration, which was our objective. Methods We included 30 patients with PD and 15 healthy controls (HC). Six cognitive domains were estimated based on neuropsychological assessment. Temporal connectivity at frontal and posterior cortical regions was estimated from a resting EEG. Results The PD group showed significant impairment for the executive, visuospatial, and language domains compared with HC. Increased connectivity at frontal regions was also found in the PD group. Frontal delta and theta connectivity negatively influenced general cognition and visuospatial performance, but this association was moderated by disease duration, with increased connectivity predicting worse performance after 8 years of disease duration. Conclusion Subtle neurophysiological changes underlie cognitive decline along PD progression, especially around a decade after motor symptoms onset. Significance Connectivity of EEG slow waves at frontal regions might be used as a predictor of cognitive decline in PD.