Does sleep apnea pave way for cognitive decline?

Researchers have found a critical link between obstructive sleep apnea during the rapid-eye-movement stage of sleep and early signs of brain changes associated with cognitive decline.

Their study suggests that low oxygen levels—known as hypoxemia—during REM sleep may contribute to injury in brain regions vital to memory, even in older adults without cognitive impairment.

“We may have found a missing piece of the puzzle.”

Obstructive sleep apnea is when throat muscles relax during sleep, blocking the airway and causing a person to wake up repeatedly to breathe. This disrupted sleep pattern can lower oxygen levels, which in turn can damage small blood vessels in the brain.

While the study does not prove that sleep apnea causes this degeneration, it does show an association.

The findings in Neurology come from the Biomarker Exploration in Aging, Cognition and Neurodegeneration study, which focused on white matter hyperintensities—a form of cerebrovascular damage detectable by MRI—and structural changes in the medial temporal lobe, a region essential for memory formation.

“Sleep apnea is important because low oxygen levels during sleep can harm the ability of our brain and bodies to function properly,” says co-corresponding author Bryce A. Mander, assistant professor of psychiatry and human behavior at the University of California, Irvine.

“Obstructive sleep apnea is a sleep disorder that increases with age. Our study found that low oxygen levels from obstructive sleep apnea may be linked to cognitive decline due to damage to the small blood vessels in the brain and the downstream impact of this damage on parts of the brain associated with memory.”

Co-corresponding author Michael Yassa, UC Irvine professor of neurobiology and behavior and director of the campus’s Center for the Neurobiology of Learning & Memory, adds: “We may have found a missing piece of the puzzle. Low oxygen during REM sleep seems to harm tiny blood vessels in the brain, and that damage shows up in areas we rely on for memory. This might help explain why even mild sleep apnea can impact brain health long before memory problems show up.”

Sleep and memory

The study included 37 people with an average age of 73 who did not have cognitive impairment. They participated in overnight sleep studies and received advanced brain imaging. Of the group, 24 people had obstructive sleep apnea.

The researchers discovered that lower oxygen levels during REM sleep—not just the number of breathing interruptions—were most strongly linked to increased white matter hyperintensities, especially in the frontal and parietal lobes. These brain regions are highly active during REM sleep and especially vulnerable to low oxygen.

This vascular damage was also associated with thinning in the entorhinal cortex, a brain area often affected early in Alzheimer’s disease. Participants with thinner entorhinal cortices showed poorer overnight memory retention, suggesting that sleep-related oxygen deprivation might impair the brain’s ability to consolidate memories.

“REM sleep is when your brain does some of its most important cleanup and memory storage work,” says co-corresponding author Destiny E. Berisha, a doctoral researcher in neurobiology and behavior at UC Irvine. “If oxygen levels drop during that time, we may be interrupting critical maintenance for the brain’s memory systems.”

A hidden risk

The research raises questions about how obstructive sleep apnea is typically diagnosed and treated. Many patients with obstructive sleep apnea have a mild apnea-hypopnea index score, the standard clinical measure of sleep apnea severity. But this study found that even those with mild scores experienced significant drops in oxygen during REM sleep, which were linked to brain changes.

“This is important, because we often rely on this to determine treatment,” Mander says. “Our findings show that focusing solely on the number of breathing events may miss the true physiological harm being done—especially during REM sleep.”

Alzheimer’s prevention

The study supports a growing body of evidence linking sleep disorders and dementia. The entorhinal cortex, which showed the strongest relationship to sleep-related damage, is one of the first regions affected by Alzheimer’s pathology. The researchers believe their findings could help explain how untreated sleep apnea may raise Alzheimer’s risk over time.

The authors stress that more research is needed in larger, more diverse populations and in people with more severe forms of obstructive sleep apnea. However, their results underscore the need to rethink how sleep apnea is evaluated and managed in older adults.

“Most research on sleep apnea is focused on the early part of the night, dominated by non-REM sleep,” Yassa says.

“Our data suggest we may need to pay closer attention to what happens during REM sleep, when the brain may be most vulnerable.”

Multiple grants from the National Institute on Aging and the American Academy of Sleep Medicine Foundation supported the research. The authors thank participants in the Biomarker Exploration in Aging, Cognition and Neurodegeneration study for their invaluable contributions.

Source: UC Irvine

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