Researchers have been searching for clues to determine risk factors that predict which patients with PD will develop cognitive decline. Understanding who is at a higher risk could lead to earlier intervention and treatment, with the goal of preserving cognitive functioning and slowing the disease progression. Previous studies have found that demographic factors such as the age of onset (with a higher age at onset more associated with cognitive decline), depression, and fewer years of education have some predictive value. In addition, mutations in the beta-glucocerebrosidase gene (GBA) have been linked to an accelerated cognitive decline in people with PD. (GBA mutations are found in about 10% of patients with PD.)1,2
Now, researchers have developed a predictive algorithm that could provide a potential test to tell which patients with PD are more likely to develop cognitive decline. The research article was recently published in Lancet Neurology, and it describes how researchers evaluated longitudinal data from 1986 to 2016 of 3,200 patients with PD from North America and Europe. The predictive model includes a person’s age at onset of PD, baseline mental ability using the Serial Mini Mental State Examination (MMSE) scores, years of education, motor exam score, sex (males are more likely to develop cognitive impairment than females), depression, and GBA mutation status. By studying the medical records of patients with PD and using the predictive model, researchers were able to create a scoring that predicts cognitive impairment within 10 years of the onset of disease.1
Creating a scoring system
Each of the seven variables contributed to the score in the predictive model. Age of onset counted for 56.5% of the score, followed by the baseline mental ability (MMSE score) of 7.7%. Other factors counted for smaller percentages but were still important contributors: years of education (5.4%), motor exam score (4.7%), sex (2.6%), depression (1.9%), and GBA mutation status (1.5%).
The cognitive risk score showed a high accuracy for predicting whether a patient with PD will develop cognitive impairment within 10 years of the onset of their disease. Higher scores had an increased risk compared to those in the lowest scoring bracket. Of those with the scores in the lowest bracket, 95.8% survived for 10 years without global cognitive impairment, while only 34.9% of those with scores in the highest bracket didn’t have cognitive impairment at the 10-year mark.1
Benefits of the predictive scoring system
This new research and the development of a potential scoring system to predict cognitive decline is an important step in understanding PD. The predictive algorithm is based on variables that have been previously identified and proven through evidence to be correlated with cognitive impairment in PD, and the predictive scoring is non-invasive, allowing for implementation in any research setting that has access to a gene-testing laboratory. In addition, researchers have developed a clinical variables-only version that can be used when gene testing is not available. The new scoring system may be of great benefit to clinical trials that are focusing on restoring or slowing cognitive decline in people with PD.1
Not ready for routine clinical care
While the predictive scoring system provides important information that can help researchers, the study authors note that it is not yet ready for use in routine clinical care of people with PD. Additional studies are first needed to confirm the data. Also, while a low score on the predictive model may provide reassurance for some patients and family members, a high score has limited value for an individual patient. It is not yet known whether modifying any of the risk factors, such as education level or using a treatment aimed at GBA mutations, may impact the cognitive outcome.1
About cognitive decline in Parkinson’s disease
Cognitive changes are one of the most debilitating symptoms of Parkinson’s disease (PD). While not everyone with PD experiences cognitive changes, those who do experience cognitive decline may have difficulties with processing or responding to information, language dysfunction, trouble maintaining focus, memory problems, or difficulty in planning, organizing or regulating behavior to meet certain goals. Cognitive decline in people with PD is associated with a lower quality of life and a higher degree of nursing home placement, caregiver distress, and mortality.1,3
The study authors of the new predictive model are hopeful that in the near future, data-driven prediction of cognitive decline will inspire new research efforts in proactive and preventive methods of treating PD.1
Liu G, et al. Prediction of cognition in Parkinson's disease with a clinical–genetic score: a longitudinal analysis of nine cohorts. Lancet Neurology. Aug 2017;16(8):620-629.
Zhu K, van Hilten JJ, Marinus J. Predictors of dementia in Parkinson’s disease; ndings from a 5-year prospective study using the SCOPA-COG. Parkinsonism Relat Disord 2014; 20: 980–85.
Watson GS, Leverenz JB. Profile of cognitive impairment in Parkinson disease. Brain Pathol. 2010 May; 20(3): 640–645.