“Significant cognitive impairment is a dreaded outcome for Parkinson’s disease patients,” says Daniel Weintraub, Professor of Psychiatry at the University of Pennsylvania’s Perelman School of Medicine. “We need to do all that we can to understand this key non-motor feature of the disease and to develop better treatments and preventive strategies.” To that end, Weintraub and his colleagues are investigating the neurobiology of cognitive changes – and the effort has led to a new set of biomarkers that could help predict which patients are most likely to suffer cognitive decline (1).
The team found four distinct biomarkers, each independently associated with cognitive impairment over the study’s three-year duration: dopamine deficiency, lower levels of β-amyloid protein in the cerebrospinal fluid (CSF), and single nucleotide polymorphisms in the COMT and BDNF genes. In addition, decreased brain volume or thickness upon imaging was also associated with impairment. “We now have evidence that changes in the dopamine system, Alzheimer’s disease pathology, and unrelated genetic factors all contribute independently to cognitive decline in Parkinson’s disease.” So is there potential for a clinical test – for diagnosis, prognosis, or therapeutic monitoring? Potentially all of the above, says Weintraub. “It is relatively simple and inexpensive to obtain blood (for genotyping), a brain structural MRI (for atrophy and thickness) and CSF (for Alzheimer’s disease biomarkers). Any of these biomarkers, singly or as a group, could help predict present and future cognitive decline.” As to monitoring treatments, the potential is certainly there, but Weintraub notes that additional studies will need to determine whether the biomarkers predict response to, or are affected by, cognitive-enhancing medications. If such a test were developed, it would be of greatest use in patients with early-stage Parkinson’s disease, before significant cognitive impairment has occurred. Weintraub foresees an additional application, though. “It will also be helpful when we have pathology-specific treatments, such as amyloid- or synuclein-focused compounds, when we need to know the specific neural substrate for cognitive impairment at an individual level.” The first step along that path is to follow a larger number of patients for a longer period of time, so that the researchers can see whether or not these same factors predict not just cognitive decline over a three-year period, but also conversion to dementia – an even more serious outcome.
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References
- C Caspell-Garcia et al., “Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease”, PLoS One, 12, e0175674 (2017). PMID: 28520803.
