Alzheimer Biomarkers Linked to Sleep-Disordered Breathing

Daniel M. Keller, PhD

June 11, 2013

PHILADELPHIA, Pennsylvania — Sleep-disordered breathing in healthy elderly subjects is associated with several biomarkers for Alzheimer's disease, leading researchers to think that sleep-disordered breathing might be a risk factor for the development of dementia.

But the reverse is also possible. It might be that "preclinical Alzheimer's increases or starts sleep-disordered breathing, but then sleep-disordered breathing makes things worse and produces brain injury and accumulation of amyloid beta," said Ricardo Osorio, MD, from the New York University Langone School of Medicine, in New York City.

Dr. Osorio and his colleagues conducted a cross-sectional study of 68 healthy elderly subjects. The results were presented here at the American Thoracic Society 2013 International Conference.

All subjects underwent clinical examinations, neuropsychologic testing, home monitoring for sleep-disordered breathing, and testing for biomarkers of Alzheimer's disease, including cerebrospinal fluid amyloid beta-42, p-tau, t-tau, positron emission tomographic imaging with fluorodeoxyglucose for brain hypometabolism and with Pittsburgh compound B, and structural magnetic resonance imaging.

To diagnose sleep-disordered breathing, researchers used the apnea–hypopnea index (AHI4%), which measures the number hourly episodes of sleep-disordered breathing with at least 4% oxygen desaturation.

Of the 68 healthy elderly participants, 26.5% had normal breathing during sleep, but 48.5% had mild sleep-disordered breathing (AHI4%, 5 - 15) and 25.0% had moderate to severe sleep-disordered breathing (AHI4%, >15).

Body mass index was higher in those with moderate to severe sleep-disordered breathing than in those with mild sleep-disordered breathing (< .05), but otherwise, there was no difference in terms of neuropsychologic tests or clinical parameters.

Only a few biomarkers of Alzheimer's disease were found in the obese subjects. However, in subjects with a body mass index below 25 kg/m², the pattern of biomarkers was "very similar to what we see in people who are facing Alzheimer's disease," Dr. Osorio reported.

Lean subjects showed hippocampal atrophy, hypometabolism in the medial temporal lobe and the posterior cingulate cortex — regions that are usually very sensitive to risk for Alzheimer's disease — and an increase in p-tau and t-tau in the cerebrospinal fluid. In contrast, in obese subjects, glucose hypometabolism was significant only in the medial temporal lobe (< .01).

Table. Biomarkers for Alzheimer's Disease in Lean Subjects

Biomarker P value
Increased cerebrospinal fluid p-tau .02
Glucose hypometabolism  
   Alzheimer's disease-vulnerable regions .05
   Medial temporal lobe <.01
   Lateral temporal lobe .04
   Posterior cingulate cortex/precuneus <.01


Dr. Osorio noted that he does not think that obesity protects against Alzheimer's disease or that being lean is detrimental. "I think that in the group of lean subjects, we are probably seeing people who have signs of preclinical Alzheimer's, and preclinical Alzheimer's is one of the reasons sleep-disordered breathing goes up late in life," he speculated.

The good news is that sleep-disordered breathing can be treated with continuous positive airway pressure (CPAP). "If we treat subjects with CPAP and see changes in the biomarkers, we could be talking about a new therapy for the prevention of Alzheimer's. I don't think it will cure Alzheimer's, but it may delay the disease many years, which would be very beneficial," Dr. Osorio said.

"This is only one probable contributing factor to something that is most likely multifactorial, yet may represent a potential therapeutic target in the toolbox of the Alzheimer's physician," said Susheel Patil, MD, clinical director of pulmonary and critical care medicine at Johns Hopkins Bayview Medical Center in Baltimore, Maryland, who was asked by Medscape Medical News for comment. He was not involved in the study.

He noted that sleep apnea results in intermittent periods of hypoxia. It turns out that the hippocampus is extremely sensitive to hypoxia, so there seems to be a biologic plausibility to sleep apnea being a risk factor for the development or acceleration of Alzheimer's disease, he said.

The reverse could also be true, Dr. Patil explained. Because this is a cross-sectional study, it could be that Alzheimer's disease affects the development of sleep-disordered breathing.

Dr. Osorio noted that sleep is very important for memory processing, and for brain health in general, so it makes sense that a sleep disorder would affect the brain and memory systems.

Dr. Patil pointed out that animal and human studies have demonstrated that certain brain structures are particularly sensitive to the effects of hypoxia. So far, however, no connection between hypoxia and impaired cognition has been established.

Because no clear therapeutic target exists for Alzheimer's disease and because the field is moving toward finding earlier targets to prevent disease onset or progression, sleep-disordered breathing might be a good place to look, Dr. Patil said.

This study received no commercial funding. Dr. Osorio and Dr. Patil have disclosed no relevant financial relationships.

American Thoracic Society (ATS) 2013 International Conference: Abstract A2320. Presented May 19, 2013.


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