Alzheimer's & Dementia

Link between Alzheimer’s and sleep apnea affirmed in brain tissue study

Brain tissue analysis revealed sleep apnea generates similar patterns of toxic protein accumulation to what researchers see in Alzheimer's disease
Brain tissue analysis revealed sleep apnea generates similar patterns of toxic protein accumulation to what researchers see in Alzheimer's disease

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.

Source: RMIT

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6 comments
undrgrndgirl
i'm beginning to think everything is linked to alzheimer's disease...or nothing.
since we don't really know what alz is it's hard to know what's a risk.
Kpar
Considering the number of people I know using CPAPs (a surprisingly large number, including some young, fit people!), this needs to be researched more extensively. Alzheimer's has been on the increase- perhaps because people are living longer (?), but we need to get ahead of this trend.
Karmudjun
Nice article Rich. Sleep apnea's contribution to diabetes, heart disease, hypertension, and overall inflammation states has been well known so this article opens another avenue for research. However, looking at the sleep apnea syndrome as causative doesn't appear to be the best use of our time - we know obesity is a major contributing factor as is oropharyngeal tone. Central sleep apnea would have more of a pathological relationship to all neurological disorders, not just Alzheimers - so while this is a low powered study (too few subjects, no specificity for obstructive versus central sleep apnea, and a 'snapshot' sample since the only way to enroll in an autopsy study is to die first) it may open up another area of research.

But I think this avenue of research will just prove more of the same. We already know untreated sleep apnea contributes to metabolic disorders like HTN, DM, CAD, and Dementias, and that treated sleep apnea may increase one's lifespan by a combination of improving your sleep while slowing the progression into the metabolic syndrome(s). If we can lengthen one's life with devices like CPAPs and BiPAPs, we will find the oldsters will develop all of the metabolic & stress related diseases as they age. We need to find the key to reducing our 'self destructive lifestyles' impact on developing full blown Parkinson's, Alzheimers, Lewy body dementia, and so on. I'd rather not die of old age without awareness of where I am or who you are, and this kind of study doesn't answer any therapeutic questions.
KurtCannon
I have not heard any more about the Australian research team that learned ultrasound dissolves amyloid and tau plaque and reverses the cognitive decay. Being 72 I would like to know about this treatment.
P51d007
I'm in my early 60's. I got a smartwatch 2 years years ago, when the price dropped on the one I wanted, but was going to send it back as just a "fad". First couple days, NOT having to reach or pull out my phone to see who was calling, texting, emailing to me, was worth it. Noticed the "health" app and started tracking my sleep. It SUCKED! I was waking up 3-5 times a night, for what I thought was to "go to the bathroom". Plus, I noticed my heart rate DURING SLEEP, would pop up into the 90bpm a few times. On a routine checkup, I told my doctor, showed them what I had on my phone and they signed me up for a sleep study. I've been on a CPAP for almost a year and it's my BEST FRIEND! I routinely sleep though the night without waking, deep sleep is much better, and my resting heart rate stays in the low to mid 50's now. Also not tired during the day. Amazing piece of technology, CPAP machines.
Hugh Lynas
I am in my 88th year on this planet and have had sleep apnea for 25 years (treated with a CPAP machine). My brain is as sharp as it ever was - I do daily projects, talk with family, ride my bike, drive to stores, live life very much the way I have always done. I do have some short term memory issues, which are pretty common in people in my age bracket - "why did I come into this room?", "Gee, I can't remember his name - I know who you are talking about but..."Honey I went down for the wine but forgot it!" I know this does not prove anything, but the connection theory between Alzheimer's and sleep apnea is obviously not absolute. Thank God.