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

J Neurol. 2022 Dec;269(12):6530-6543. doi: 10.1007/s00415-022-11301-w. Epub 2022 Aug 14.

Abstract

Background: 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.

Objective: We investigated whether neuroimaging and plasma biomarkers correlate with individual task-specific cognitive domain declines evidenced by computerized neuropsychological tests in PD patients.

Methods: 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.

Results: 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).

Conclusions: Cognitive decline in PD patients has a task-specific correlation with neuroimaging and plasma biomarkers, which may implicate the underlying neuropathological process of PDD.

Keywords: Biomarkers; CANTAB; Cognition; Parkinson’s disease; Plasma.

MeSH terms

  • Biomarkers
  • Cerebral Cortical Thinning
  • Cognition
  • Cognitive Dysfunction* / complications
  • Cognitive Dysfunction* / etiology
  • Humans
  • Neuroimaging
  • Neuropsychological Tests
  • Parkinson Disease* / complications
  • Parkinson Disease* / diagnostic imaging
  • Parkinson Disease* / pathology
  • alpha-Synuclein

Substances

  • alpha-Synuclein
  • Biomarkers