Biomarkers for cognitive dysfunction in Parkinson's disease

Abstract

Introduction: Cognitive dysfunction is among the most prevalent and debilitating non-motor features of Parkinson's disease (PD). The neuropathological correlates of cognitive dysfunction in PD are being revealed by clinicopathological correlation studies. These findings are fostering the development of candidate biomarkers to facilitate diagnosis of cognitive impairment and dementia, and to predict cognitive decline and onset of dementia in PD.

Methods: A literature review of candidate biomarkers for cognitive dysfunction in PD was performed based on a PubMed search for peer-reviewed articles published from 1997 to June 2017 using the search terms "biomarker", "parkinson", and "dementia".

Results: Based on the neuropathological correlates of cognitive dysfunction in PD, significant efforts are underway to identify biomarkers that reflect the presence and degree of 1) proteinopathy (i.e., abnormal protein aggregation), 2) neurodegeneration, including neuronal loss and axonal degeneration (i.e., involvement of gray matter and white matter, respectively), 3) neurotransmitter deficiency (e.g., acetylcholine and dopamine), and 4) abnormalities of brain function and connectivity.

Conclusion: The complexity of multiple substrates of cognitive impairment and dementia in PD will likely preclude the simplicity of a single biomarker. Thus, increased efforts to develop and validate combined biomarkers and predictive algorithms are anticipated.

Keywords: Biomarker; CSF; Dementia; MRI; Mild cognitive impairment; Neuropathology; PET; Parkinson.