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Treating OSA with positive airway pressure decreased amyloid levels in CSF



Soluble amyloid-beta in cerebrospinal fluid (CSF) decreased when subjects with obstructive sleep apnea used a positive airway pressure device with good adherence, suggesting that improving sleep could reduce the risk of Alzheimer’s disease in this population.

A patient wears a CPAP device yelo34/ThinkStock

The small decrease in cerebrospinal amyloid-beta 40 (Ab40) and Ab42 hints at decreased neuronal release of the neurotoxic protein, wrote Yo-El S. Ju, MD, and her colleagues. The report was published online in Annals of Neurology.

Alzheimer’s disease (AD) biomarker studies typically find decreased CSF levels associated with increased Ab brain plaques. But before plaques form, increased soluble Ab in CSF is a risk factor for aggregation. Thus, higher soluble Ab levels in mid-life may suggest a risk of later Ab pathology, wrote Dr. Ju of Washington University, St. Louis.

“We tested individuals without any AD pathology as assessed by Ab42 [in CSF], a highly sensitive biomarker of amyloid plaques,” Dr. Ju and her coauthors wrote. “This means our study findings can be extrapolated to the large population of people with OSA [obstructive sleep apnea], many of whom are middle-aged or younger, and have many years to accrue benefit from AD risk reduction ... The effect of OSA on SWA [slow wave activity], Ab, and possibly tau, is a probable proximal step in a cascade whereby OSA increases the risk of AD.”

The researchers recruited 35 subjects with mild to severe OSA and without abnormal Ab levels in CSF. Subjects used auto-titrating positive airway pressure (PAP) for 1-4 months; 18 were sufficiently compliant to be included in the analysis (more than 4 hours on more than 70% of 30 preceding nights as recorded by the machine). CSF was obtained after a baseline polysomnogram and after the treatment period lasting 1-4 months.

Of the 18 analyzed patients, 7 had mild OSA and 11 had moderate to severe OSA. They were an average of nearly 57 years old with a mean body mass index of 30.4 kg/m2; 7 patients had hypertension.

PAP treatment was effective, indicated by a normalized apnea-hypopnea index and decreased time in hypoxemia. Total sleep time and sleep efficiency were unchanged, but slow-wave activity did increase. As expected, hourly arousals and time in hypoxemia decreased, and hypoxic nadir shifted from an oxygen saturation of 82.5% to 91%.

“As a group, there was no significant change in Ab with treatment,” the researchers wrote. But a correlational analysis found that “greater improvement in OSA was associated with greater decrease in Ab40 and Ab42. Additionally, we found that change in tau negatively correlated with OSA improvement.”

The team suggested a two-factor model to explain the relationship between OSA and Ab levels. “Due to decreased SWA, there would be relatively increased release of Ab into the [interstitial fluid]. However, as OSA severity worsens, pressure effects of obstructive respiratory events impede the clearance of Ab and tau out of the interstitial space, resulting in lower levels in the CSF and an inverse U-shaped curve. In this model, a small improvement in OSA may result in an increase in Ab or tau, whereas a larger improvement in OSA – that ameliorates both SWA and clearance mechanisms – will result in a decrease in Ab and tau.”

The project was funded in part by Philips-Respironics, which provided the devices, and by the National Institutes of Health. Philips-Respironics had no input or role in any other part of the study. The authors had no financial disclosures.

SOURCE: Ju YS et al. Ann Neurol. 2018 Dec 31. doi: 10.1002/ana.25408.

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