Biomarkers Revealed for Cognitive Impairment in PD

Biomarkers have been identified that could predict the cognitive impairment typical of Parkinson's Disease (PD), a neurodegenerative disease that affects about half a million people in the USA, with approximately 50,000 people receive a PD diagnosis every year.

While there is no cure for PD, there are therapies that aim to slow down the advancement of the disease. Usually, however, PD is diagnosed when the symptoms become apparent, by which time the neurons affected have already been lost. This reduces the effectiveness of treatments that aim to delay PD's progression.

Scientists at the University of Pennsylvania and their colleagues examined 423 patients from 33 international centers for movement disorder, who had recently been diagnosed with PD. The patients had no symptoms of cognitive decline at the beginning of the study, in 2010. The patients were clinically followed for three years. In order to assess the predictive potential of certain biomarkers, the team conducted a series of tests.

The investigators analyzed 11 single nucleotide polymorphisms (SNPs, or genetic variations) that had been previously associated with cognition in PD. Cerebrospinal fluid (CSF) biomarkers were measured using the xMAP INNO-BIA AlzBio3 immunoassay for total tau, p-tau181 and beta-amyloid 1–42 (Aβ42). Finally, they ran a range of brain scans, including magnetic resonance imaging (MRI) and computed tomography (CT). They studied dopamine transporters, which are proteins that control the dynamic of the dopamine neurotransmitter in the brain and whose abnormal levels have been previously associated with PD. They also examined the volume and thickness of the brain.

The scientists found biomarkers that predicted cognitive decline including a deficiency in dopamine, a "diffuse" decrease in the brain volume across the frontal, temporal, parietal, and occipital lobes, pathological levels of beta-amyloid plaques which is similar to those found in Alzheimer's disease and some genetic variations. The study also found SNPs in the Catechol-O-methyltransferase (COMT) and Brain-derived neurotrophic factor (BDNF) genes, which had been previously shown to correlate with cognitive impairment.

Daniel Weintraub, MD, an associate professor of psychiatry and the lead investigator said, “Cognitive impairment in de novo Parkinson's disease increases in frequency 50% to 200% in the first several years of disease depending on the definition used, and is independently predicted by biomarker changes related to nigrostriatal or cortical dopaminergic deficits, global atrophy due to possible widespread effects of neurodegenerative disease, co-morbid Alzheimer's disease amyloid plaque pathology, and a mix of genetic factors.” The study was published on May 17, 2017, in the journal Public Library of Science ONE.