The progression of Parkinson disease and response to medication varies widely across individuals, which can make the prediction of disease course challenging.
A new study has found that some factors detectable at diagnosis may predict progression of Parkinson disease (PD). Mollenhauer and colleagues1 found that, in particular, cardiovascular risk factors like hypertension and diabetes, as well as elevated uric acid and markers of inflammation were linked to PD progression over four years.
“Our study is observational and exploratory, but upon independent validation patients should be informed in the early stages of PD about the need to immediately start reducing their cardiovascular risk factors including optimal control of blood pressure and type 2 diabetes,” wrote first author Brit Mollenhauer, MD, of Paracelsus-Elena-Klinik (Kassel, Germany), and colleagues with the DeNoPa Study Group.
“[C]linicians should pay attention to lifestyle interventions, including nutritional and physical activity in middle age even before the onset of PD,” they advised
The progression of PD and response to medication varies widely across individuals, which can make the prediction of disease course challenging. Current research suggests that the most important risk factors for progression include age and extent of motor symptoms at baseline. However, most studies so far have been small and have evaluated only a limited number of factors.
To investigate the issue in a larger group of patients, researchers conducted the De Novo Parkinson (DeNoPa) study. The single-center study took place between 2009 and 2012 at the Paracelsus-Elena-Klinik in Kassel, Germany. The study included 135 participants aged 40 to 85 years with PD diagnosed within the past six months, matched by age, sex and education with 109 healthy controls.
Researchers evaluated the annual rate of progression of motor symptoms using the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III), and cognitive symptoms using the Mini-Mental Status Examination (MMSE). They also looked at 44 baseline predictors of progression, which included sociodemographics, comorbidities, motor/nonmotor symptoms, sleep issues, MRI findings, serum and CSF biomarkers. Independent neurologists conducted followup evaluations at 24 and 48 months.
• Baseline predictors of motor progression specific to PD:
• Baseline Predictors of cognitive decline specific to PD:
The authors noted that these factors may be related to each other. While urate is an important natural antioxidant, high levels of it have been associated with increased incidence of cardiometabolic issues like hypertension, CAD, metabolic syndrome, obesity and insulin resistance. These disorders are usually associated with inflammation. Elevated CRP is a marker of increased inflammation and has been linked to decreased life expectancy and death in PD.
However, the study was observational and cannot determine why these predictors may be linked to progression in PD. The authors mentioned several factors related to PD progression that need further study. These include investigating the role of protein aggregation in PD progression, how medical comorbidities like diabetes contribute to failure of neuroprotective medication, and whether interventions to decrease CV risk can improve progression of PD.
Take Home Points
• The DeNoPa study found seven baseline factors specific to PD that were predictive of disease progression in patients with newly diagnosed PD
• Baseline factors predictive of motor progression included male sex, CAD, elevated blood pressure, and elevated serum uric acid
• Baseline factors predictive of cognitive progression included elevated CRP, elevated fasting glucose, and elevated HbA1c
• Further studies are needed, but newly diagnosed patients with PD may benefit from interventions to reduce CV risk
1. Mollenhauer B, Zimmermann J, Sixel-DÃ¶ring F, et al. Baseline predictors for progression 4 years after Parkinson's disease diagnosis in the De Novo Parkinson Cohort (DeNoPa). Mov Disord. 2018 Nov 23. [Epub ahead of print].