Biomarker Identified for Early Cognitive Decline in Parkinson's Disease

By LabMedica International staff writers
Posted on 09 Mar 2016

Identifying biomarkers for cognitive impairment could be instrumental in facilitating both early diagnosis of mild cognitive impairment and developing new cognitive-enhancing treatments.

Many patients with Parkinson's disease (PD) develop mild cognitive impairment (MCI) or dementia and cerebrospinal fluid (CSF) markers beta-amyloid42 (Aβ42), total tau protein (t-tau), phosphorylated tau protein (p-tau), and α-synuclein reflect pathophysiological changes relevant to cognition in PD.

Image: Left: A healthy neuron with the alpha-synuclein (green) protein diffusely spread in the cell. The bright reddish dots are the garbage disposal lysosomes with alpha-synuclein entering, which gives them an orange hue. Right: This is a defective neuron from a Parkinson’s brain. The lysosomes are enlarged and puffy because the alpha-synuclein is stuck outside and unable to enter the lysosomes (Photo courtesy of the US National Institute of Health).

Scientists at the Haraldsplass Deaconess University Hospital (Bergen, Norway) and their colleagues investigated the development of biomarkers of progression in PD, and the study was comprised of 414 patients with untreated PD without dementia and 196 health control (HC) subjects from 24 clinical sites worldwide. The patients were evaluated for multiple cognitive skills, including visuospatial functions, verbal memory, executive function, and attention. Patients were defined as having MCI (PD-MCI) if they showed impairment on two or more tests, while patients not fulfilling criteria for MCI were classified as having normal cognition (PD-NC).

The investigation determined that lower α-synuclein was associated with reduced performance in cognition testing in the whole PD-group. Aβ42 was significantly decreased in PD with mild cognitive impairment compared with controls, while values in PD without MCI were identical to the HC group controls. After analyzing demographics and the results of CSF analysis, there were no significant differences in gender, age, or education between PD and HC patients. Among the PD patients, 140 PD-MCI subjects were significantly older, had less formal education, and had higher Unified Parkinson's Disease Rating Scores (UPDRS) than the 274 PD-NC subjects.

Ragnhild E. Skogseth, MD, the lead investigator said, “The association between reduced CSF α-synuclein concentrations and cognition suggests that α-synuclein pathology contributes to early cognitive impairment in PD, in particular to executive-attentional dysfunction. Longitudinal analyses are needed to determine if this and other CSF biomarkers in early Parkinson's disease are associated with the risk of future cognitive decline and dementia.” The study was originally published online on November 23, 2015, in the Journal of Parkinson's Disease.

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