People who have difficulty breathing during sleep may be more vulnerable to brain changes associated with Alzheimer’s disease. New research published in Neurobiology of aging We provide evidence that sleep-disordered breathing meaningfully impacts 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, making identifying modifiable risk factors an urgent priority. Sleep breathing disorder (a general term for conditions in which breathing is repeatedly interrupted during sleep, such as obstructive sleep apnea) is now thought to be one such factor.
Previous research suggests that sleep breathing problems may promote the accumulation of a toxic protein in the brain called amyloid beta, which is a hallmark of Alzheimer’s disease. However, studies have yielded inconsistent results, and few studies have investigated how these effects differ depending on how far along an individual is already in the Alzheimer’s disease process.
To better understand this difference, a team led by Mohammad Akhradi 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 disease), and people without cognitive impairment. Of all participants, 102 reported sleep-disordered breathing and 655 did not. Importantly, the researchers excluded people who currently treat sleep apnea with devices such as CPAP, meaning the study focused on completely untreated sleep-breathing problems.
All participants underwent three types of brain imaging tests. One detects deposits of amyloid beta protein, one measures how much energy different areas of the brain use (a proxy for how active and healthy those areas are), and one measures the physical volume of brain tissue. They also completed standard tests of memory and thinking skills, along with analysis of cerebrospinal fluid (the fluid that surrounds the brain and spinal cord) to check for tau and amyloid beta proteins.
To ensure robustness, the researchers used statistical methods to create a set of 512 matched participants and compared the results of those with and without sleep-disordered breathing within each group, accounting for variables such as age, gender, and BMI.
The results revealed a complex but understandable pattern. Among cognitively healthy people or those with mild cognitive impairment, those with untreated sleep-disordered breathing had lower amyloid beta accumulation in the brain and higher brain energy activity. This suggests that during the early stages of the disease, the brain may engage in a type of compensatory response, working overtime to offset the stress caused by sleep deprivation. These people also showed widespread changes in brain tissue volume. Some areas appeared to be expanding, perhaps as the brain tried to compensate, but most were shrinking.
However, in people who had already been diagnosed with Alzheimer’s disease, the pattern was reversed, with increased amyloid-beta plaques in the brain and decreased brain energy metabolism. Additionally, their cerebrospinal fluid showed a sharp decrease in amyloid beta levels. (In Alzheimer’s disease research, low levels of this protein in spinal fluid usually indicate that it is trapped and forming toxic plaques in the brain). Three specific brain regions showed particularly strong amyloid-related effects that were directly related to lower scores on tests of memory and thinking: the precuneus, middle temporal gyrus, and fusiform gyrus.
“We hope that this complex study will prompt 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,” concluded Akradi and colleagues.
The researchers cautioned that sleep-disordered breathing was identified through self-report rather than objective sleep testing, which may underestimate the true extent of the problem, especially for people with cognitive impairments who are unable to accurately recall or report symptoms. The cross-sectional design of this study also means that the findings reflect a single snapshot in time, making it impossible to clearly establish cause and effect or to precisely track how these brain changes evolve over the lifespan.
The study, “How are self-reported sleep-disordered breathing associated with Alzheimer’s disease biomarkers?” was authored by Mohammad Akradi, Tara Farzane-Daghigh, Amir Ebneabbasi, Hanwen Bi, Alexander Drzezga, Bryce A. Mander, Simon B. Eickhoff, and Masoud Tahmasian for Alzheimer’s Disease Neuroimaging. initiative.
