A number of cerebrovascular risk factors found to be associated with a subsequent diagnosis of Alzheimer disease also showed a high association with a diagnosis of Parkinson disease, pressing the impetus for controlling these modifiable factors.
Babak Navi, MD, MS
New study results have suggested that in a similar fashion to their association in Alzheimer disease, cerebrovascular risk factors are associated with the development of Parkinson disease.
Based on findings from data including 1,035,536 Medicare beneficiaries followed for an average of 5.2 years, 1.5% were diagnosed with Parkinson and 7.9% with Alzheimer, with the majority of cerebrovascular risk factors, including stroke, atrial fibrillation, congestive heart failure, diabetes, and coronary heart disease, among others, being associated with a subsequent diagnosis of Parkinson.
Study author Babak Navi, MD, MS, chief, Division of Stroke and Hospital Neurology, Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center, told NeurologyLive that while a small proportion of Parkinson disease is the result of genetic mutation, a portion of that group shows incomplete penetrance, opening the door for the genetic mutation to show variation in symptom and disease onset.
“I think that our study's findings may be especially important for these patients and families who harbor these mutations because aggressive efforts can be made to control their cerebrovascular risk factors, which unlike the mutations, are modifiable,” Navi said. “While such an approach will first need to be evaluated in rigorously conducted clinical trials, there is a chance that it could lead to reduced risks or postponement in the subsequent development of Parkinson disease.”
Those risk factors which were associated with the highest risk were obstructive sleep apnea (hazard ratio [HR], 1.65; 95% CI, 1.56—1.75), prior stroke (HR, 1.55; 95% CI, 1.39–1.72), congestive heart failure (HR, 1.43; 95% CI, 1.31–1.55), hypertension (HR, 1.41; 95% CI, 1.32–1.50), and chronic kidney disease (HR, 1.31; 95% CI, 1.24–1.40).
“I was surprised that obstructive sleep apnea had the strongest association with subsequent Parkinson disease. There may be something unique about the link between sleep apnea and Parkinson disease pathophysiology. This should be explored in translational research studies.”
Similarly, for Alzheimer disease, the highest risk associated factors for a subsequent diagnosis were stroke (HR, 2.06; 95% CI, 1.98—2.15), congestive heart failure (HR, 1.90; 95% CI, 1.72–2.10), and hypertension (HR, 1.58; 95% CI, 1.53–1.63). Tobacco use (HR, 1.61; 95% CI, 1.57–1.66) and alcohol abuse (HR, 1.58; 95% CI, 1.52–1.64) were also highly associated with Alzheimer.
Additionally, coronary heart disease (HR, 1.28), peripheral vascular disease (HR, 1.28), atrial fibrillation (HR, 1.20), chronic obstructive pulmonary disease (HR, 1.13), diabetes (HR, 1.17), tobacco use (HR, 1.20), and valvular heart disease (HR, 1.17) were also associated with a subsequent diagnosis of Parkinson.
Ultimately, all 14 risk factors evaluated were associated with an HR above 1.05 for subsequent diagnosis of Alzheimer disease. All but 1 (alcohol abuse: HR, 0.93) had an HR above 1.00 for Parkinson, though hyperlipidemia did also result in a lower-bound confidence interval below 1.00 (HR, 1.03; 95% CI, 0.99—1.08).
“Our study is retrospective and based on claims data in an elderly Medicare population,” Navi explained. “Therefore, before it leads to changes in clinical practice, the findings from our study should be validated in a prospective cohort that includes patients of all age groups and has a longer follow-up time.”
As a negative control, Navi and colleagues additionally explored these 14 cerebrovascular risk factors with a diagnosis of renal colic, due to its unlikely biologic association with cerebrovascular disease. Most of the risk factors were not associated with it, save for chronic kidney disease (HR, 1.21) and obstructive sleep apnea (HR, 1.24).
“The takeaway message for community-based clinicians is that cerebrovascular risk factors seem to increase the risk for Parkinson disease in a similar fashion as they do for Alzheimer disease,” Navi explained to NeurologyLive. “Therefore, there is now even more impetus to prevent or control these risk factors as they not only place patients at higher risk for developing stroke and other cardiovascular events, but also neurodegenerative diseases, which are often disabling and associated with poor quality of life.”
Kummer BR, Diaz I, Wu X, et al. Associations between cerebrovascular risk factors and Parkinson disease. Ann Neurol. Published online August 29, 2019.