As the availability of potential biomarkers for Parkinson’s disease drives the debate around diagnosing prodromal Parkinson’s disease (pPD) from theory to practice, said authors of a recent study, clinicians should weigh each patient’s preferences, circumstances, and goals against the potential benefits and harms of disclosure. The study and an accompanying editorial appeared online in Neurology.
Because markers such as SNCA, LRRK2, and GBA mutations impact small subgroups of patients at risk of developing monogenic forms of Parkinson’s disease, wrote Richard N. Rees, MBChB, MD, from the Department of Clinical and Movement Neurosciences at University College London Queen Square Institute of Neurology, and colleagues, researchers are working to identify people at risk of idiopathic Parkinson’s disease using models based on known risk and protective factors. The recent development of highly accurate cerebrospinal fluid (and potentially serum) alpha-synuclein seed amplification assays, which may show Parkinson’s disease’s signature before overt symptoms appear, will reinforce these efforts, authors added.
‘Tap the Brakes’
However, sources interviewed by Neurology Reviews counseled caution with potential prodromal Parkinson’s disease biomarkers. “As the science advances in Parkinson’s disease and related disorders,” said Michael S. Okun, MD, “our ability to predict who will and will not be diagnosed will improve. We should, however, tap the brakes and consider the consequences of making a diagnosis in someone at risk — especially someone without symptoms.” Dr. Okun is National Medical Advisor to the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases at University of Florida Health in Gainesville, Florida. He was not involved with the study.
Neurologists should ask themselves why they are testing for Parkinson’s disease biomarkers, said Dr. Okun, and what counseling and shared decision-making they provided beforehand. “This already complex scenario becomes even more complicated when we consider that many people with GBA gene mutations and some with LRRK2 mutations may never actually manifest Parkinson’s disease.”
Dr. Michael S. Okun
Neurologists’ knowledge of Parkinson’s disease biomarkers remains in the research phase, said editorial co-author Colin Hoy, PhD, a postdoctoral researcher at the University of California, San Francisco, Weill Institute for Neurosciences in San Francisco, California. No one fully understands the relationships between potential biomarkers, what pathological risks they may carry, and how those risks eventually foment symptoms, he said.
Dr. Colin Hoy
The lack of disease-modifying therapies (DMTs) for Parkinson’s disease plays a critical role in whether patients want to know if they are at risk, added Dr. Hoy. In a survey of 101 patients with established Parkinson’s disease published in Neurology in 2020, 54% would have eschewed knowing about their risk in the absence of DMT.
Nevertheless, wrote Dr. Rees and colleagues, the earlier that patients with prodromal Parkinson’s disease know about it, the longer they might forestall Parkinson’s disease through nonpharmaceutical approaches. In a study published in Neurology in 2011, aerobic exercise reduced Parkinson’s disease risk. Similarly, techniques such as tai chi can significantly improve motor function, depression, and quality of life in Parkinson’s disease, according to a meta-analysis published in Parkinsonism & Related Disorders in 2017.
Having foreknowledge of Parkinson’s disease risk can empower people to manage comorbid conditions, seek evidence-based treatments, and enroll in clinical trials while their condition perhaps remains amenable to treatment, added Dr. Rees and colleagues. Patients also can proactively build support networks and address legal eventualities such as advance care directives, authors added.