A recent research shows that obstructive sleep apnea is associated with Alzheimer’s disease. The build-up of harmful compounds due to lack of oxygen is a potential explanation for the association.
A person’s breathing repeatedly stops and restarts during obstructive sleep apnea. During the day, symptoms include loud snoring, restless sleep, and sleepiness.
Estimates of the prevalence of the disease in the general population among adults differ widely, from 9 to 38 percent. Sleep apnea, however, is usually more common in males, older adults , and people with obesity.
Sleep apnea is a recognised risk factor for the development of dementia and is related to impaired concentration , memory and executive skills.
“We know that if you have mid-life sleep apnea, you are more likely to develop Alzheimer’s when you are older, and if you have Alzheimer’s, you are more likely than those of your age to have sleep apnea,” says Prof. Stephen Robinson of the RMIT University School of Health and Biomedical Sciences in Bundoora, Australia.
“The link is there, but it remains a huge challenge to untangle the triggers and biological mechanisms,” he adds.
Prof. Robinson and his colleagues recently discovered that the magnitude of the disorder correlates with decreases in the volume of the hippocampus by analyzing postmortem samples from individuals who had sleep apnea.
In individuals with Alzheimer’s, this portion of the brain, which is closely involved in memory, also atrophies.
Using the same brain extracts, the first evidence of amyloid plaques associated with sleep apnea has now been discovered by Prof. Robinson’s team.
Hallmarks of Alzheimer’s
A characteristic of the damage seen in Alzheimer’s is amyloid plaques, along with clumps of fibers known as neurofibrillary tangles.
The researchers found that the plaques first appear in the same positions and spread in the brains of people with sleep apnea in the same way as they do in people with Alzheimer’s.
Moreover, the magnitude of the plaques was associated with the severity of sleep apnea.
“It is an significant step in our understanding of the associations between these disorders and opens up new avenues for researchers working to establish treatment therapies to cure Alzheimer’s disease and potentially avoid it,” says Prof. Robinson, who led the study.
The research, a collaboration between RMIT University and the National University Hospital of Iceland in Reykjavik, was published by the authors in the journal Sleep.
Scientists investigated preserved brain samples from 34 individuals who obtained a diagnosis of obstructive sleep apnea with a mean age of 67 years. Brainstems from 24 of these individuals were eligible for analysis.
During their lifetimes, none of the patients were diagnosed with dementia. However, 70 percent had neurofibrillary tangles and in their hippocampi, 38 percent had amyloid plaques.
While some individuals may have had mild cognitive impairment or undiagnosed dementia, none had symptoms that were severe enough for official diagnosis, even though some had a density of plaques and tangles that were high enough to classify as Alzheimer’s disease, “says Prof. Robinson.” While some individuals may have had mild cognitive impairment or undiagnosed dementia, none had symptoms that were severe enough for official diagnosis.
Correlation in the hippocampus
The researchers found that the severity of sleep apnea a person suffered was significantly associated with the amount of amyloid plaque in their hippocampus after controlling for variables such as age, body mass index ( BMI) and sex.
In their hippocampus, sleep apnea associated less well with the amount of neurofibrillary tangles, and there was no important association after age change.
The researchers found that when analyzing the brainstem samples, while about two-thirds contained tangles and a fifth contained amyloid plaques, their quantities were not associated with the intensity of sleep apnea.
In Alzheimer’s disease, in a cortical region close to the hippocampus called the parahippocampal gyrus, plaques and tangles first appear. Then, before spreading to the rest of the cortex, the lesions advance to the hippocampus.
In sleep apnea, the same pattern of development appears to occur.
“We were only able to locate plaques and tangles in the cortical region near the hippocampus in cases of moderate sleep apnea, exactly where they were first identified in Alzheimer’s disease,” says Prof. Robinson.
In their paper , the researchers propose that repeated bouts of oxygen deprivation during sleep can cause oxidative stress in sleep apnea that leads to the hippocampus build-up of amyloid plaques.
“Thus, [sleep apnea] may render these areas more vulnerable to the (as yet unknown) causative agent in [Alzheimer’s], thereby facilitating the pathogenesis of this disease. This is supported by our previous findings of reduced hippocampal volume in the same brains.”
They write that, instead, the clearance of amyloid from the brain that typically occurs during sleep can interfere with sleep apnea.
Sleep helps to flush beta-amyloid from the brain, a study in mice showed. Therefore, sleep apnea can trigger a slow build up of protein by repeatedly disturbing sleep during the night.
Interestingly, the authors of the new study write that both Alzheimer’s and sleep apnea decrease the amount of fast eye movement (REM) and non-REM sleep.
The comparatively small number of brain samples solely from individuals from Iceland and a lack of control samples from people who did not have the disease were among the limitations of the research.
Prof. Robinson says his team is collaborating with a larger cohort to construct a clinical study.
One of the results of the study was that the amount of plaques and tangles found in the samples did not appear to affect a standard procedure, known as Continuous Positive Airway Pressure (CPAP).
The authors note, however, that no records of the degree or timing of CPAP usage have been recorded, so this result is unreliable.