[Central Sleep Apnea] Key to Dying While Asleep

DNC: Health News - Scientists Find Key to Dying While Asleep: "People who die in their sleep may stop breathing due to a cumulative loss of brain cells in their breathing-command post, according to a new study published in the online edition of Nature Neuroscience.

'We wanted to reveal the mechanism behind central sleep apnea, which most commonly affects people after age 65,' said Jack Feldman, the study's principal investigator and distinguished professor of neurobiology at the David Geffen School of Medicine at UCLA.

'Unlike obstructive sleep apnea -- in which a person stops breathing when their airway collapses -- central sleep apnea is triggered by something going awry in the brain's breathing center,' he explained.

Role of PreBotC Neurons

In earlier research, Feldman's team pinpointed a brainstem region as the command post for generating breathing in mammals. They dubbed it 'the preBötzinger complex,' identifying a small group of preBötC neurons responsible for issuing the commands.

In the latest study, they examined the role of the preBötC neurons in generating breathing during sleep. Their goal was to determine what would happen if these brain cells were destroyed.

The researchers injected adult rats with a cell-specific compound to target and kill more than half of their specialized preBötC neurons and then monitored the animals' breathing patterns. After four or five days, they saw dramatic results.
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'We were surprised to see that breathing completely stopped when the rat entered REM sleep, forcing the rat to wake up in order to start breathing again,' said Leanne McKay, postdoctoral fellow in neurobiology.

'Over time, the breathing lapses increased in severity, spreading into non-REM sleep and eventually occurring when the rats were awake, as well,' she noted.

Cumulative Cell Deficit

The rat findings are relevant to the human brain because mammals' brains are organized in a similar fashion, say the scientists. Rats possess 600 specialized preBötC cells, and humans have a few thousand, Feldman theorizes, which slowly deteriorate over a lifetime.

"Our research suggests that the preBötzinger complex contains a fixed number of neurons that we lose as we age," he said. "Essentially, we sped up these cells' aging process in the rats over several days instead of a lifetime."

Long before the rats had difficulty breathing when awake, they developed a breathing problem during sleep. The same thing happens as people grow older, the researchers believe.

"We speculate that our brains can compensate for up to a 60 percent loss of preBötC cells, but the cumulative deficit of these brain cells eventually disrupts our breathing during sleep," Feldman said.

"There's no biological reason for the body to maintain these cells beyond the average lifespan, and so they do not replenish as we age," he observed. "As we lose them, we grow more prone to central sleep apnea."
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True Cause of Death Undetected

When elderly, but otherwise healthy, people die during sleep, physicians commonly record the cause of death as heart failure. But the loss of preBötC neurons sparks central sleep apnea in many cases, according to the UCLA researchers, and the true cause of death goes undetected.

Central sleep apnea also may strike people suffering the late stages of neurodegenerative disorders, such as Parkinson's disease, Lou Gehrig's disease and multiple system atrophy -- all serious conditions that lead to movement problems.

"People with these diseases breathe normally when they are awake, but many of them have breathing difficulties during sleep," said Wiktor Janczewski, assistant researcher in neurobiology.

"When central sleep apnea strikes, they are already very ill and their sleep‑disordered breathing may go unnoticed," he pointed out.

"As the patients grow sicker, their nighttime threshold for wakefulness rises. Eventually, their bodies reach a point when they are unable to rouse themselves from sleep when they stop breathing, and they die from lack of oxygen," Janczewski suggested.

The UCLA team will repeat their research with elderly rats in order to learn why central sleep apnea first strikes during REM sleep. They also plan to analyze the brains of people who die from neurodegenerative diseases to determine whether these patients show damage in their preBötzinger complexes.

The National Heart, Lung and Blood Institute funded the research.

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