Link between sleep apnea and dementia, according to a study in mice

by University of Queensland

Urotensin II-saporin induces specific lesions of cholinergic neurons at mesopontine tegmentum. A Diagrams and photomicrographs of coronal sections of the brainstem, the right column being immunostained for ChAT-positive neurons within the laterodorsal tegmental nucleus (LDT) following unilateral direct injection of UII-saporin (UII-SAP) into the right mesopontine tegmentum (MPT). Scale bar = 200 μm. Images are representative of N = 3 animals. B Direct injection bilateral of UII-SAP into the MPT reduces the number of ChAT-positive neurons within the LDT compared with Blank-SAP injections (P < 0.0001). C Intraventricular injection of UII-SAP reduced the number of ChAT-positive neurons within the LDT compared to control unconjugated saporin injections (Blank-SAP) (P = 0.0003). D Direct injection of UII-SAP into the LDT does not affect the number of calbindin-positive GABAergic neurons in the LDT compared to Blank-SAP injection (P = 0.8857). E The number of ChAT-positive hypoglossal motor neurons per section following injection of UII- SAP or Blank-SAP is not different (P = 0.9470). F The distance traveled by UII-SAP- and Blank-SAP-injected mice in the center area of the open field test, which was not different between conditions (P = 0.8313). G Time spent on the Rotarod in three successive trials lasting up to 3 min each is not different between UII-SAP- and Blank-SAP-injected mice. Comparisons by Students’ unpaired two-tailed t-test; ****P < 0.0001, n.s., non-significant. Results are presented as mean ± s.e.m. Each data point represents an individual animal. Credit: Nature Communications (2022). DOI: 10.1038/s41467-022-33624-y

Researchers at The University of Queensland have discovered a link between obstructive sleep apnea and an increased risk of developing dementia.

Professor Elizabeth Coulson from UQ’s Queensland Brain Institute and School of Biomedical Sciences and her team found a causal relationship between a lack of oxygen to the brain during sleep and Alzheimer’s disease in mice.

“We found sleep deprivation alone in mice caused only mild cognitive impairment,” Professor Coulson said.

“But we developed a novel way to induce sleep-disrupted breathing and found the mice displayed exacerbated pathological features of Alzheimer’s disease.

“It demonstrated that hypoxia—when the brain is deprived of oxygen—caused the same selective degeneration of neurons that characteristically die in dementia.”

Professor Coulson said the next step would be to determine what levels of hypoxia result in brain degeneration in humans.

“It’s estimated around 50% of elderly people have obstructive sleep apnea, when their throat muscles intermittently collapse and block the airway during sleep causing their breathing to stop and start,” she said.

The current gold standard treatment is a CPAP (continuous positive airway pressure) machine, which keeps the airway open during sleep and allows oxygen to the brain.

“We couldn’t fit CPAP to mice, but we experimentally prevented the hypoxia and this stopped the cognitive impairment and neuron death, and also reduced the Alzheimer’s pathology,” Professor Coulson said.

“This suggests that CPAP treatment of obstructive sleep apnea has the potential to reduce dementia risk.”

Professor Coulson said the findings could change the way dementia clinicians diagnose and treat their patients.

“Thirty percent of people with obstructive sleep apnea being fitted for CPAP machines already display signs of dementia-like cognitive impairment,” she said.

“Unfortunately the hospital system isn’t referring those people to dementia clinics.

“Some dementia clinicians have reported their patient’s memory has improved after their sleep problems were identified and treated.”

Professor Coulson said not everyone with obstructive sleep apnea would get dementia.

“But we need to define the ‘at risk’ population,” she said.

“Early stage human trials are underway with sleep clinicians in Brisbane and Sydney to determine the correlation between hypoxia and sustained cognitive impairment, and whether CPAP can reduce dementia risk.

“I would strongly recommend anyone with obstructive sleep apnea use a CPAP machine to maintain cognitive function, as well as assist with other health issues.”

The study has been published in Nature Communications.