Untreated Sleep Apnea Nearly Doubles Parkinson Disease Risk
Key Clinical Summary
- JAMA Neurology (VA cohort, 11.3M veterans): Obstructive sleep apnea (OSA) increased Parkinson disease (PD) incidence by ~1.9-fold (HR 1.92; 95% CI 1.55–2.38; P < 0.001) over 6 years, equating to 1.61 additional PD cases/1000 vs those without OSA.
- CPAP treatment within 2 years of diagnosis lowered PD incidence by ~30%, reducing cases from 9.10 to 6.81 per 1000 (P < 0.001).
- Authors emphasized that early OSA diagnosis and CPAP use may enhance neuronal resilience, potentially mitigating neurodegenerative risk from chronic nocturnal hypoxia.
Obstructive sleep apnea (OSA) appears to nearly double the risk for later development of Parkinson disease (PD), but early continuous positive airway pressure (CPAP) treatment may attenuate that risk by 30%. Findings from the study of US veterans were published in JAMA Neurology.
“It’s not at all a guarantee that you’re going to get Parkinson disease, but it significantly increases the chances,” said co-author Gregory Scott, MD, PhD, assistant professor of pathology, Oregon Health & Science University (OHSU) School of Medicine, and pathologist at the VA Portland.
In the United States, an estimated 50 million people have OSA, with as many as 80% going undiagnosed. Concurrently, Parkinson disease is the fastest-growing neurological disorder worldwide, with an estimated 1 million people affected nationwide. The 2 conditions are hypothesized to be associated in some manner due to similar biological patterns. For example, people with OSA exhibit elevated levels of total and phosphorylated a-synuclein in plasma, as well as reduced striatal dopamine transporter availability.
Study Design and Results
To “rigorously test” the association between OSA and PD, as well as assess risk modification by CPAP, the authors designed a cohort study that utilized the US Department of Veterans Affairs Corporate Data Warehouse nationwide electronic health record (EHR) database. OSA diagnosis was determined by the relevant administrative code, while CPAP usage was determined from a semi-structured medical interview field in the HER. The primary outcome was cumulative incidence of PD, calculated while adjusting for competing risk of death after balancing for age, race, sex, and smoking status.
A total of 11,310,411 veterans (1,109,543 female [9.8%]) with a mean (SD) age of 60.5 (14.7) years were included in analyses. The mean (SD) follow-up for the study population was 4.9 (1.8) years. Of the included veterans, 1,552,505 (13.7%) had OSA. Veterans with OSA demonstrated 1.61 additional cases of PD (point estimate; 95% CI, 1.13-2.09; hazard ratio [HR] 1.92 [95% CI, 1.55-2.38; P < 0.001) at 6 years from diagnosis per 1000 people compared to those without OSA.
As for the effect of CPAP usage on PD risk, authors observed that initiation of CPAP within 2 years of initial OSA diagnosis significantly reduced incident PD compared to those who did not use CPAP, with a reduction of 2.28 cases of PD (OSA-no CPAP: 9.10; 95% CI, 8.18-10.01 vs OSA-CPAP: 6.81; 95% CI, 5.43-8.19; P < 0.001).
Expert Commentary
“If you stop breathing and oxygen is not at a normal level, your neurons are probably not functioning at a normal level either,” said lead author Lee Neilson, MD, assistant professor of neurology at OHSU and a staff neurologist at the Portland VA. “Add that up night after night, year after year, and it may explain why fixing the problem by using CPAP may build in some resilience against neurodegenerative conditions, including Parkinson disease.”
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