A new study confirms links between obstructive sleep apnea and Alzheimer’s disease. Possible reasons for the association include the build up of toxic products due to lack of oxygen.
In obstructive sleep apnea, a person’s breathing repeatedly stops and restarts. Symptoms include loud snoring, restless sleep, and sleepiness during the day.
Estimates of the condition’s prevalence among adults in the general population vary widely, from 9–38%. However, sleep apnea is typically more common among males, older people, and individuals with obesity.
Sleep apnea has links to poor attention, memory, and executive skills, and is a recognized risk factor for the development of dementia.
“We know that if you have sleep apnea in mid-life, you’re more likely to develop Alzheimer’s when you’re older and if you have Alzheimer’s, you are more likely to have sleep apnea than other people your age,” says Prof. Stephen Robinson of the School of Health and Biomedical Sciences at RMIT University in Bundoora, Australia.
“The connection is there, but untangling the causes and biological mechanisms remains a huge challenge,” he adds.
By studying postmortem samples from people who had sleep apnea, Prof. Robinson and his colleagues recently discovered that the severity of the condition correlates with reductions in the volume of the hippocampus.
This part of the brain, which is closely involved in memory, also atrophies in people with Alzheimer’s.
Using the same brain samples, Prof. Robinson’s team has now found the first evidence of amyloid plaques associated with sleep apnea.
Amyloid plaques are a hallmark of the damage seen in Alzheimer’s, together with clumps of fibers known as neurofibrillary tangles.
The researchers discovered that the plaques appear first in the same locations and spread in the same way in the brains of people with sleep apnea as they do in people with Alzheimer’s.
In addition, the extent of the plaques correlated with the severity of sleep apnea.
“It’s an important advance in our understanding of the links between these conditions and opens up new directions for researchers striving to develop therapies for treating and hopefully preventing Alzheimer’s disease,” says Prof. Robinson, who led the research.
The authors published the study, which was a collaboration between RMIT University and the National University Hospital of Iceland in Reykjavik, in the journal Sleep.
The scientists investigated preserved brain samples from 34 people with a mean age of 67 years who had received a diagnosis of obstructive sleep apnea. Brainstems were available for study from 24 of these individuals.
None of the patients had received a diagnosis of dementia during their lifetimes. However, 70% had neurofibrillary tangles and 38% had amyloid plaques in their hippocampi.
“While some people may have had mild cognitive impairment or undiagnosed dementia, none had symptoms that were strong enough for an official diagnosis, even though some had a density of plaques and tangles that were sufficiently high to qualify as Alzheimer’s disease,” says Prof. Robinson.
After adjusting for factors such as age, body mass index (BMI), and sex, the researchers found that severity of sleep apnea a person experienced significantly correlated with the amount of amyloid plaque in their hippocampus.
Sleep apnea correlated less well with the number of neurofibrillary tangles in their hippocampus, and there was no significant correlation after adjusting for age.
When examining the brainstem samples, the researchers found that although about two-thirds contained tangles and a fifth contained amyloid plaques, their amounts did not correlate with the severity of sleep apnea.
In Alzheimer’s disease, plaques and tangles first appear in a cortical area close to the hippocampus called the parahippocampal gyrus. The lesions then progress to the hippocampus, before spreading to the rest of the cortex.
The same pattern of progression seems to occur in sleep apnea.
“In cases of mild sleep apnea, we could only find plaques and tangles in the cortical area near the hippocampus, precisely where they are first found in Alzheimer’s disease,” says Prof. Robinson.
In their paper, the researchers speculate that in sleep apnea, repeated bouts of oxygen deprivation during sleep may cause oxidative stress that leads to the build up of amyloid plaques in the hippocampus.
“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, alternatively, sleep apnea may disrupt the clearance of amyloid from the brain that normally occurs during sleep.
A study in mice found that sleep helps to flush beta-amyloid from the brain. By repeatedly disturbing sleep throughout the night, sleep apnea may therefore cause a slow build up of the protein.
Interestingly, the authors of the new study write that the amount of rapid eye movement (REM) and non-REM sleep reduces in both Alzheimer’s and sleep apnea.
Among the study’s limitations were the relatively small number of brain samples solely from people from Iceland and a lack of control samples from people who did not have the condition.
Prof. Robinson says his team is working towards establishing a clinical study with a larger cohort.
One of the study’s findings was that a common treatment, known as Continuous Positive Airway Pressure (CPAP), did not appear to affect the number of plaques and tangles found in the samples.
However, the authors note that there were no records of the extent or timing of CPAP use, so this finding is unreliable.