A task-specific cognitive domain decline is correlated with plasma and neuroimaging markers in patients with Parkinson's disease.

Abstract

Cognitive impairment is a disabling non-motor symptom of Parkinson's disease (PD). It remains uncertain whether declines in specific cognitive domains relate to imaging or plasma biomarkers across the disease continuum. We investigated whether neuroimaging and plasma biomarkers correlate with individual task-specific cognitive domain declines evidenced by computerized neuropsychological tests in PD patients. A total of 107 participants, including 87 PD patients (30 with normal cognition [PD-NC], 30 with mild cognitive impairment [PD-MCI], 27 with dementia [PDD]), and 20 healthy controls, were recruited. All received the Cambridge Neuropsychological Test Automatic Battery (CANTAB) test, brain MRI, and assays of plasma biomarkers, including α-synuclein, tau, Aβ42, and Aβ40. PD patients had generally poorer cognitive performance than controls. Patients with PD-MCI and PDD had worse performance in visual, verbal, and working memory and executive function than those with PD-NC. After adjusting for covariates, PDD patients had global cortical thinning, especially in the temporal and parietal lobes, and higher plasma α-synuclein levels and tau:Aβ42 ratios than PD-NC group. Plasma α-synuclein level was associated with frontal lobe-mediated tasks, while the tau:Aβ42 ratio was associated with posterior cortical-mediated tasks. Facial emotion recognition tasks and visual pattern recognition associated with frontotemporal cortical thinning. The accuracy of predicting PDD using age alone (area under the curve [AUC] 0.756) increased by incorporating plasma biomarkers (AUC = 0.851, p = 0.025). Cognitive decline in PD patients has a task-specific correlation with neuroimaging and plasma biomarkers, which may implicate the underlying neuropathological process of PDD.