Men With Obstructive Sleep Apnea May be at Risk of Early Cognitive Decline

Ivana Rosenzweig, PhD

Results from a recently published study in Frontiers in Sleep demonstrated that middle-aged men with obstructive sleep apnea (OSA) without comorbidities showed distinct cognitive changes, including deficits in attention, executive function, and memory.¹ The findings suggest that distinct OSA-driven processes, particularly when OSA is severe, may be sufficient for cognitive changes to occur as early as middle age, in otherwise healthy male patients.²

Among 27 men, 16 were diagnosed with mild OSA and 11 patients were diagnosed with severe OSA. Results revealed that the patients with severe OSA had poorer vigilance, executive functioning, short-term visual recognition memory, and social and emotion recognition compared with matched controls. Patients with mild OSA performed better in the domains compared with those who had severe OSA, although worse than the controls.

“We show poorer executive functioning and visuospatial memory and deficits in vigilance, sustained attention, and psychomotor and impulse control in men with OSA. Most of these deficits had previously been ascribed to co-morbidities,” said senior author Ivana Rosenzweig, PhD, neuropsychiatrist and head of the Sleep and Brain Plasticity Centre at King’s College London in a statement.¹ “We also demonstrated for the first time that OSA can cause significant deficits in social cognition.”

In patients with different OSA severities, the preliminary analysis of cognitive parameters was taken from the multimodal clinical study, InCOSA (NCT02967536). A group of men between the ages of 35 and 70 years old with a de novo diagnosis of mild to severe OSA and no comorbidities were recruited from the study. The participants were nonsmokers or nonalcohol abusers, were mildly somnolent, and not obese (body mass index [BMI] lower than 30). The researchers studied a group of 7 age-, BMI-, and education-matched men without OSA for 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.²

Diagnosis of OSA was performed via WatchPAT test for patients’ respiratory function during sleep, and also through a video-polysomnography in the sleep center at King's College. During sleep, patients had their brain waves studied and measured by electroencephalography (EEG), while investigators recorded was blood oxygen levels, heart rate, breathing, and eye and leg movements. In addition, the researchers analyzed the participants’ cognitive function with the Cambridge Neuropsychological Test Automated Battery (CANTAB) tests.

“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 in a statement.¹

Researchers noted that the occurrence of cognitive deficits might be because of intermittent low oxygen and high carbon dioxide in the blood, blood flow changes to the brain, sleep fragmentation, and neuroinflammation in patients with OSA. Whether comorbidities had similar negative effects on cognition above and beyond those caused directly by OSA is not yet clear, according to the study investigators.

Rosenzweig and colleagues concluded OSA is sufficient to cause cognitive deficits in middle-aged men regardless of their health status. Compared with previous research, the most common comorbidities of OSA were reported as systemic hypertension, cardiovascular and metabolic diseases, and type 2 diabetes.³

Patients with OSA experience common symptoms such as restless sleep, loud snoring, daytime sleepiness, and prolonged headaches in the morning. Current research shows that it may occur in as much as between 15% and 30% in men and between 10% and 15% in women, or approximately 1 billion adults worldwide, of whom an estimated 80% are underdiagnosed. Some of the major risk factors for OSA include patients who are at middle or old age, are obese, a smoker, have chronic nasal blockage, high blood pressure, and are a male.¹

“Our study is a proof of concept. However, our findings suggest that comorbidities likely worsen and perpetuate any cognitive deficits caused directly by OSA itself,” said Rosenzweig in a statement.¹ “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 OSA patients with or without comorbidities.”

REFERENCES
1. Obstructive sleep apnea may directly cause early cognitive decline. News Release. Published April 6, 2023. Accessed May 10, 2023. Frontiers. https://blog.frontiersin.org/2023/04/06/frontiers-sleep-obstructive-sleep-apnea-cognitive-decline/
2. Gnoni, V, Mesquita, M, O’Regan D, et al., 2023. Distinct cognitive changes in male patients with obstructive sleep apnoea without co-morbidities. Front Sleep. Published 2023 April 6. doi: 10.3389/frsle.2023.1097946
3. Bucks RS, Olaithe M, Rosenzweig I, Morrell MJ. Reviewing the relationship between OSA and cognition: Where do we go from here?. Respirology. 2017;22(7):1253-1261. doi:10.1111/resp.13140