Link between Alzheimer’s and sleep apnea affirmed in brain tissue study
A new study, from a team of Australian and Icelandic scientists, is offering some of the strongest evidence to date linking Alzheimer’s disease and sleep apnea. The research, based on studying autopsied brain tissue, shows how the toxic protein aggregations commonly associated with Alzheimer’s seem to start and spread in the same way in the brains of patients with sleep apnea.
"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," explains Stephen Robinson, lead investigator on the new research. "The connection is there but untangling the causes and biological mechanisms remains a huge challenge.”
A large number of PET imaging studies have found sleep apnea does seem to correlate with higher levels of the toxic proteins in the brain commonly associated with Alzheimer’s disease. This new research offers a granular insight into how similar these Alzheimer’s-like pathologies are in older subjects with sleep apnea.
The study analyzed post-mortem brain tissue from over 30 subjects with an average age of 67 and clinically verified obstructive sleep apnea. At time of death none of the subjects were displaying clinical signs of cognitive decline or dementia.
The focus of the analysis was on the hippocampus and the brainstem, two regions known to present some of the earliest pathogenic signs of Alzheimer’s. The researchers were looking for signs of the two primary pathological indicators of Alzheimer’s – amyloid plaques and neurofibrillary tau tangles.
"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 Robinson.
Interestingly, the volume of amyloid in the hippocampus served as an effective predictor for the severity of sleep apnea in a given subject. Tau and amyloid were found in the brainstem samples also, however, these burdens did not correlate with sleep apnea severity.
Another compelling finding from the study was the detection of similar volumes of amyloid plaques and tau tangles regardless of whether a subject was treating their apnea with a CPAP device. The researchers suggest this particular result should be interpreted with caution as there is prior evidence CPAP treatment for sleep apnea can slow cognitive decline in mild Alzheimer’s patients.
The big unanswered question hovering over this kind of research is whether sleep apnea is an early symptom of Alzheimer’s or whether it is a separate contributing risk factor. Previously researchers have suggested longer temporal studies are needed to answer this “chicken and egg problem.”
Robinson points out, although none of the subjects is this new study were clinically diagnosed with Alzheimer’s or dementia at their time of death, that doesn’t mean they weren't presenting with very early signs of the degenerative disease.
"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 Robinson.
There is certainly a solid causal hypothesis to explain how sleep apnea could accelerate the onset of Alzheimer’s disease. We know that one of the functions of deep slow wave sleep is to clear the brain of toxic proteins. We also know subjects suffering from sleep apnea may not effectively reach deep sleep stages due to the disruptions caused by phases of interrupted breathing.
Robinson suggests this new study solidifies our understanding of the links between sleep apnea and cognitive decline but it is still early days for this field of research. We may now have a clearer understanding of how these two conditions contribute to neurodegeneration, but exactly how to translate the findings into clinical treatments to prevent cognitive decline is still unclear.
"The next stage for our research will be to continue analyzing these samples to get a full understanding of the neuropathology, including signs of inflammation and changes to the blood vessels that supply nutrients to the brain,” says Robinson. "The sample size for this study was limited, so we would also like to work towards establishing a clinical study with a larger cohort."
The new study was published in the journal Sleep.