September 16, 2020
Obstructive sleep apnea (OSA) treatment with positive airway pressure (PAP) therapy was associated with a lower odds of incident Alzheimer's disease and other dementia in a large retrospective cohort study of Medicare patients with the sleep disorder.
The study builds on research linking OSA to poor cognitive outcomes and dementia syndromes. With use of a 5% random sample of Medicare beneficiaries (more than 2.7 million) and their claims data, investigators identified approximately 53,000 who had an OSA diagnosis prior to 2011.
Of these Medicare beneficiaries, 78% with OSA were identified as "PAP-treated" based on having at least one durable medical equipment claim for PAP equipment. And of those treated, 74% were identified as "PAP adherent" based on having more than two PAP equipment claims separated by at least a month, said Galit Levi Dunietz, PhD, MPH, at the virtual annual meeting of the Associated Professional Sleep Societies.
Dr. Dunietz and her coinvestigators used logistic regression to examine the associations between PAP treatment and PAP treatment adherence, and incident ICD-9 diagnoses of Alzheimer's disease (AD), mild cognitive impairment (MCI), and dementia not otherwise specified (DNOS) over the period 2011-2013.
After adjustments for potential confounders (age, sex, race, stroke, hypertension, cardiovascular disease, and depression), OSA treatment was associated with a significantly lower odds of a diagnosis of AD (odds ratio, 0.78; 95% confidence interval 0.69-0.89) or DNOS (OR, 0.69; 95% CI, 0.55-0.85), as well as nonsignificantly lower odds of MCI diagnosis (OR, 0.82; 95% CI, 0.66-1.02).
"People who are treated for OSA have a 22% reduced odds of being diagnosed with AD and a 31% reduced odds of getting DNOS," said Dr. Dunietz, from the University of Michigan in Ann Arbor, in an interview after the meeting. "The 18% reduced odds of mild cognitive disorder is not really significant because the upper bound is 1.02, but we consider it approaching significance."
Adherence to treatment was significantly associated with lower odds of AD, but not with significantly lower odds of DNOS or MCI, she said. OSA was confirmed by ICD-9 diagnosis codes plus the presence of relevant polysomnography current procedural terminology code.
All told, the findings "suggest that PAP therapy for OSA may lower short-term risk for dementia in older persons," Dr. Dunietz and her co-nvestigators said in their poster presentation. "If a causal pathway exists between OSA and dementia, treatment of OSA may offer new opportunities to improve cognitive outcomes in older adults with OSA."
Andrew W. Varga, MD, of the division of pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai and the Mount Sinai Integrative Sleep Center, both in New York, said that cognitive impairment is now a recognized clinical consequence of OSA and that OSA treatment could be a target for the prevention of cognitive impairment and Alzheimer's disease in particular.
"I absolutely bring it up with patients in their 60s and 70s. I'm honest -- I say, there seems to be more and more evidence for links between apnea and Alzheimer's in particular. I tell them we don't know 100% whether PAP reverses any of this, but it stands to reason that it does," said Dr. Varga, who was asked to comment on the study and related research.
An analysis published several years ago in Neurology from the Alzheimer's Disease Neuroimaging Initiative cohort found that patients with self-reported sleep apnea had a younger age of MCI or AD onset (about 10 years) and that patients who used continuous positive airway pressure had a delayed age of onset. "Those who had a subjective diagnosis of sleep apnea and who also reported using CPAP as treatment seemed to go in the opposite direction," said Dr. Varga, a coauthor of that study. "They had an onset of AD that looked just like people who had no sleep apnea."
While this study was limited by sleep apnea being self-reported -- and by the lack of severity data -- the newly reported study may be limited by the use of ICD codes and the fact that OSA is often entered into patient's chart before diagnosis is confirmed through a sleep study, Dr. Varga said.
"The field is mature enough that we should be thinking of doing honest and rigorous clinical trials for sleep apnea with cognitive outcomes being a main measure of interest," he said. "The issue we're struggling with in the field is that such a trial would not be short."
There are several theories for the link between OSA and cognitive impairment, he said, including disruptions in sleep architecture leading to increased production of amyloid and tau and/or decreased "clearance" of extracellular amyloid, neuronal sensitivity to hypoxia, and cardiovascular comorbidities.
Dr. Dunietz's study was supported by The American Academy of Sleep Medicine Foundation. She reported having no disclosures. Dr. Varga said he has no relevant disclosures.