Untreated sleep apnea linked to physical brain changes in Alzheimer’s disease

People who have difficulty breathing during sleep may be more vulnerable to the brain changes associated with Alzheimer’s disease. New research published in Neurobiology of Aging provides evidence that sleep-disordered breathing has a meaningful effect on key brain and spinal fluid markers of the condition across different stages of cognitive decline.

Alzheimer’s disease is the most common cause of dementia, and identifying modifiable risk factors has become an urgent priority. Sleep-disordered breathing — an umbrella term for conditions where breathing is repeatedly interrupted during sleep, including obstructive sleep apnea — is now thought to be one such factor.

Previous research suggested that sleep breathing problems might accelerate the build-up of a toxic protein called amyloid-beta in the brain, a hallmark of Alzheimer’s disease. However, studies have produced inconsistent results, and few have examined how these effects differ depending on how far along the Alzheimer’s disease process an individual already is.

To better understand this distinction, a team led by Mohammad Akradi of Shahid Beheshti University in Tehran analyzed data from 757 participants enrolled in the Alzheimer’s Disease Neuroimaging Initiative, a large collaborative research database.

The sample included people with Alzheimer’s disease, mild cognitive impairment (a condition that can be a precursor to Alzheimer’s), and cognitively unimpaired individuals. Of all the participants, 102 reported having sleep-disordered breathing and 655 did not. Importantly, researchers excluded anyone currently treating their sleep apnea with devices like a CPAP machine, meaning the study focused entirely on untreated sleep breathing issues.

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All participants had undergone three types of brain imaging: one to detect amyloid-beta protein deposits, one to measure how much energy different brain regions were using (a proxy for how active and healthy those regions are), and one to measure the physical volume of brain tissue. They also completed a standard test of memory and thinking ability, alongside an analysis of their cerebrospinal fluid (the liquid surrounding the brain and spinal cord) to check for tau and amyloid-beta proteins.

To ensure robustness, the researchers created 512 matched sets of participants using a statistical technique, comparing outcomes between those with and without sleep breathing problems within each group to account for variables like age, sex, and body mass index.

The results revealed a complex but telling pattern. Among those who were cognitively healthy or had mild cognitive impairment, those with untreated sleep breathing problems had lower amyloid-beta build-up in the brain and higher brain energy activity. This suggests that in the earlier stages of disease, the brain may be mounting a kind of compensatory response, working in overdrive to offset the stress caused by poor sleep. These individuals also demonstrated widespread alterations in brain tissue volume—mostly shrinkage, though some areas appeared enlarged, possibly as the brain attempted to compensate.

However, in those already diagnosed with Alzheimer’s disease, the pattern reversed: amyloid-beta brain plaques were higher, and brain energy metabolism was lower. Furthermore, their cerebrospinal fluid showed a steeper drop in amyloid-beta levels. (In Alzheimer’s research, lower levels of this protein in the spinal fluid typically indicate that it is getting trapped and forming toxic plaques inside the brain). Three specific brain regions — the precuneus, the middle temporal gyrus, and the fusiform gyrus — showed particularly strong amyloid-related effects that were directly linked to poorer scores on the memory and thinking test.

“We hope that this multimodal study incentivizes clinicians to consider the importance of screening and treating individuals with sleep disordered breathing as potential therapeutic targets to reduce the burden of Alzheimer’s disease,” Akradi and colleagues concluded.

The researchers cautioned that sleep-disordered breathing was identified through self-report rather than objective sleep testing, which likely underestimates the true extent of the problem, particularly in those with cognitive impairment who may not accurately recall or report their symptoms. The study’s cross-sectional design also means the findings reflect a single snapshot in time, making it impossible to definitively establish cause and effect or track exactly how these brain changes evolve over a lifespan.

The study, “How is self-reported sleep-disordered breathing linked with biomarkers of Alzheimer’s disease?,” was authored by Mohammad Akradi, Tara Farzane-Daghigh, Amir Ebneabbasi, Hanwen Bi, Alexander Drzezga, Bryce A. Mander, Simon B. Eickhoff, and Masoud Tahmasian, for the Alzheimer’s Disease Neuroimaging Initiative.