Obstructive sleep apnea may directly cause early cognitive decline

Obstructive sleep apnea is a potentially dangerous condition. During sleep, the throat muscles of people with obstructive sleep apnea relax and block the airflow into the lungs, so that they repeatedly stop breathing. Common symptoms of obstructive sleep apnea include restless sleep, loud snoring, daytime sleepiness, and prolonged headaches in the morning – highly debilitating for patients and their partners.

Obstructive sleep apnea is currently underdiagnosed: it may occur in as much as 15% to 30% of men and 10% to 15% of women, or approximately 1 billion adults worldwide, of whom an estimated 80% don’t know they have it. Major risk factors for obstructive sleep apnea include middle or old age, being obese, smoking, chronic nasal blockage, high blood pressure, and being male.

Now, researchers from the UK, Germany, and Australia have shown for the first time that in middle-aged men, obstructive sleep apnea can also cause early cognitive decline, even in patients who are otherwise healthy and not obese. The results are published in Frontiers in Sleep.

“We show poorer executive functioning and visuospatial memory and deficits in vigilance, sustained attention, and psychomotor and impulse control in men with obstructive sleep apnea. Most of these deficits had previously been ascribed to co-morbidities,” said Dr. Ivana Rosenzweig, a neuropsychiatrist who heads the Sleep and Brain Plasticity Centre at King’s College London, and the lead author of the study.

“We also demonstrated for the first time that obstructive sleep apnea can cause significant deficits in social cognition.”

Rare cohort without comorbidities

Rosenzweig and colleagues studied a group of 27 men between the ages of 35 and 70 with a new diagnosis of mild to severe obstructive sleep apnea but without any comorbidities. Such patients are relatively rare because most men and women with obstructive sleep apnea have comorbidities such as cardiovascular and metabolic disease, stroke, diabetes, chronic systemic inflammation, or depression.

The men were not currently smokers or alcohol abusers and were not obese (ie, with a body mass index (BMI) below 30). As a control, the researchers studied a group of seven age-, BMI-, and education-matched men without obstructive sleep apnea. The obstructive sleep apnea diagnosis was confirmed by a so-called WatchPAT test of their respiratory function during sleep at home, and also by video-polysomnography at King's College sleep center. With the latter method, the brain waves of sleeping subjects were measured by electroencephalography (EEG), while their blood oxygen levels, heart rate, breathing, and eye and leg movements were tracked.

The scientists also tested the subjects’ cognitive function with the CANTAB or "Cambridge Neuropsychological Test Automated Battery" of tests.

Premature cognitive decline

The results showed that patients with severe obstructive sleep apnea had poorer vigilance, executive functioning, short-term visual recognition memory, and social and emotion recognition than the matched controls. Patients with mild obstructive sleep apnea performed better in these domains than patients with severe obstructive sleep apnea, but worse than the controls.

“The most significant deficits…were demonstrated in the tests that assess both simultaneous visual matching ability and short-term visual recognition memory for nonverbalizable patterns, tests of executive functioning and cued attentional set-shifting, in vigilance and psychomotor functioning, and lastly, in social cognition and emotion recognition,” wrote the authors.

The authors conclude that obstructive sleep apnea is sufficient to cause these cognitive deficits, which previous studies had attributed to the most common comorbidities of obstructive sleep apnea, such as systemic hypertension, cardiovascular and metabolic diseases, and type 2 diabetes.

Unclear mechanism

But what is the mechanism by which obstructive sleep apnea causes premature cognitive decline? The authors speculated that the cognitive deficits are due to intermittent low oxygen and high carbon dioxide in the blood, changes in blood flow to the brain, sleep fragmentation, and neuroinflammation in patients with obstructive sleep apnea.

“This complex interplay is still poorly understood, but it’s likely that these lead to widespread neuroanatomical and structural changes in the brain and associated functional cognitive and emotional deficits,” said Rosenzweig.

Whether comorbidities have similar negative effects on cognition above and beyond those caused directly by obstructive sleep apnea is not yet clear.

“Our study is a proof of concept. However, our findings suggest that comorbidities likely worsen and perpetuate any cognitive deficits caused directly by obstructive sleep apnea itself,” said Rosenzweig.

“What remains to be clarified in future studies is whether comorbidities have an additive or synergistic effect on the latter deficits and whether there is a difference in brain circuitry in obstructive sleep apnea patients with or without comorbidities.”

Source: News Release
FRONTIERS
April 6, 2023