BLOOD AND CEREBROSPINAL FLUID BIOMARKERS OF COGNITIVE IMPAIRMENT IN PARKINSON’S DISEASE

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease, characterized by
dopaminergic neuronal loss in substantia nigra and α-synuclein accumulation in intraneuronal aggregates.
Apart from the cardinal motor symptoms, non-motor features are also evident; among them, cognitive
impairment is a consistent finding in PD patients, who are susceptible to an increased dementia risk.
Progressing cognitive decline includes the stages of subjective cognitive decline, mild cognitive impairment
(MCI) and dementia. Various mechanisms contribute to each of these stages, whereas responsible
neuropathological correlates have been investigated in clinicopathological correlation studies. Longitudinal
studies focus on the prognostic value of different molecules in assessments of cognitive decline over time.
The composition of the cerebrospinal fluid (CSF) reflects brain metabolism and neuronal condition; hence,
CSF proteins may be promising biomarkers of cognitive dysfunction mechanisms in PD. Plasma and serum
studies have also revealed candidate biomarkers for assessing cognition in PD. Since MCI conversion to
dementia is variable, biomarkers that enhance early identification of cognitive dysfunction factors and
prediction of dementia risk are necessary. This review summarizes recent studies of promising blood and
CSF biomarkers of PD-related cognitive impairment. Several correlates of neuronal damage have been
shown indicative of poor cognitive performance and predicted cognitive deterioration, including amyloid-β
and neurofilament light chain. Inflammatory factors, lysosomal dysfunction, oxidative stress and genetic
variants could be also useful in assessing cognitive decline in PD. Future research is needed for the validation
of the candidate biomarkers, recognizing the potential benefit of robust biomarkers in clinical practice and
their implementation in clinical trials.