Sleep Apnea May Boost Alzheimer's Risk

Megan Brooks

November 10, 2017

A new study suggests that obstructive sleep apnea (OSA) may have a role in amyloid accumulation in the brain, increasing the risk for Alzheimer's disease (AD).

In a longitudinal study of cognitively normal older adults, biomarkers of increased amyloid burden increased over time in those with OSA in proportion to OSA severity.

"Clinical interventions aimed at OSA (such as treatment with continuous positive airway pressure [CPAP] or dental appliances) could mitigate the progression of cognitive impairment and delay the onset of the disease," Ricardo Osorio, MD, senior study author, from the Center for Brain Health, NYU Langone Health in New York City, told Medscape Medical News.

The study was published online November 10 in the American Journal of Respiratory and Critical Care Medicine.

A Cause of Amyloid Deposition?

The researchers investigated cross-sectional and longitudinal associations between OSA severity and changes in cerebrospinal fluid (CSF) and Pittsburgh compound B positron emission tomography (PiB-PET) biomarkers of AD in 208 healthy, cognitively normal adults aged 55 to 90 years.

 Ninety-seven (46.6%) participants were free of OSA (apnea-hypopnea index [AHI] < 5) and were considered healthy controls; 76 (36.5%) had mild OSA (AHI, 5 to 14.9) and 35 (16.8%) had moderate to severe OSA (AHI ≥ 15).

Baseline OSA severity was associated with 2-year longitudinal decreases in CSF Aβ42 and a trend toward increases in cortical PiB-PET uptake — changes "potentially consistent with increased brain amyloid burden," which were also observed in a subset of individuals who underwent amyloid PET imaging.

These findings suggest that OSA "may play a role in amyloid deposition in late-life," the researchers write. They note that the magnitude of these changes was higher than that predicted by the presence of the apolipoprotein ε4 allele alone, which to date is considered the most important risk factor for sporadic AD.

Although OSA severity was associated with increases in brain amyloid burden, it was not predictive of cognitive decline over time. "This is not completely surprising," write the authors, "given that the relationship between amyloid burden and cognition is probably nonlinear and dependent on additional factors such as tau pathology and microvascular changes."

Dr Osorio told Medscape Medical News that several cross-sectional or epidemiologic studies have suggested that sleep disturbances might contribute to amyloid deposits and accelerated cognitive decline in those at risk for AD. But it's been challenging to verify causality for these associations because OSA and AD share risk factors and commonly coexist.

"This study uses objective measurements of sleep (home monitoring for OSA and actigraphy) and is longitudinal (measures AD biomarkers over time) so it is one of the first to show in humans that, at least in cognitively normal individuals, it is the sleep that might be driving the amyloid deposition and not vice versa," Dr Osorio told Medscape Medical News.  Therefore, treating OSA might delay the progression to mild cognitive impairment (MCI) or dementia in the elderly, he said.

OSA "Extremely Common" in the Elderly

Commenting on the findings for Medscape Medical News, Luca Giliberto, MD, PhD, neurologist at Northwell Health's Neuroscience Institute in Manhasset, New York, said the study is "well done and from a clinical perspective there is nothing really surprising."

"Sleep apnea is a risk factor for vascular brain disease. From a pathophysiological perspective, it is important because it confirms in another model of brain hypoxia, which is sleep apnea, that oxidative stress and hypoxia can be risks for worsening of Alzheimer's pathology," he said. "I think one of our duties as physicians is to ask all of our patients consistently about their sleep habits."

OSA is "extremely common" in the elderly and most don't know they have it, Ronald Chervin, MD, from the University of Michigan Sleep Disorders Center in Ann Arbor and past president of the American Academy of Sleep Medicine, told Medscape Medical News.

"What we have only begun to understand in more recent years are two important developments," said Dr Chervin. "First, that inadequate sleep is a risk factor for future transition from normal cognition to MCI, and from MCI to Alzheimer's, and second, that the 'glymphatic system' — essentially the interstitial flow of fluid outside and around neurons and glia in the brain, during sleep — serves each night to wash out metabolic byproducts, including some related to amyloid."

"The fascinating finding in this study," said Dr Chervin, "is that this highly common, underdiagnosed sleep disorder — OSA — could be an impactful cause of amyloid accumulation in the brain."

"The study was not designed to assess cause and effect definitively, but the correlation between OSA severity and longitudinal changes in both CSF Aβ42 levels and brain amyloid burden suggests that OSA could be causing these changes," Dr Chervin added.

"If so, this provides mechanistic insight into the observations from other studies that poor sleep can precede MCI or Alzheimer's. Even more importantly, the findings fuel speculation that identification and treatment for OSA could reduce risk for development of Alzheimer's disease. I think these are exciting findings to say the least."

The study was supported by the National Institutes of Health, Foundation for Research in Sleep Disorders, American Sleep Medicine Foundation , and Friedman Brain Institute. The authors, Dr Chervin , and Dr Giliberto have disclosed no relevant financial relationships .

Am J Respir Crit Care Med. Published online November 10, 2017. Abstract

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