Sleep Apnea May Increase Alzheimer's Risk

NOVEMBER 13, 2017
Matt Hoffman
Ricardo Osorio, MDRicardo Osorio, MD
Everyone knows that getting a good night of sleep is important - perhaps more so than we thought. New data has shown that obstructive sleep apnea (OSA) may increase the risk of developing Alzheimer’s disease (AD) in the elderly.

Using biomarkers for amyloid beta (Aß), investigators found that while OSA severity did not predict cognitive deterioration, it was associated with increases in brain amyloid burden over 2 years of follow-up. The findings suggest that clinical interventions could be helpful in the prevention of amyloid build up in the elderly.

Ricardo Osorio, MD, study author and an assistant professor of psychiatry at New York University School of Medicine, told MD Magazine that “this study uses objective measurements of sleep and is longitudinal (it 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.”

The study population included 208 patients with normal cognition (Clinical Dementia Rating [CDR] = 0). Patients were given a sleep evaluation consisting of the Epworth Sleepiness Scale (ESS), as well as a lumbar puncture (LP) and measurements of cerebral spinal fluid (CSF) amyloid beta (Aß42). 

At baseline, 97 patients were OSA free (apnea/hypopnea index with 4% desaturation [AHI4%] <5) and considered controls, while 76 had mild OSA (AHI4% 5 to 15) and 35 had moderate-to-severe OSA (AHI4% >15). In total, more than half of the population had OSA (53%).

“The prevalence of OSA in the elderly is very high, ranging from 30% to 80% depending on how you define it. In addition, in most cases the patient is asymptomatic, meaning that most subjects are not sleepy during the day and are not aware that they are suffering from this condition,” Osorio said. “In a person at risk for AD and OSA, clinical interventions aimed at OSA such as treatment with [continuous positive airway pressure] or dental appliances could mitigate the progression of cognitive impairment.”

Of the total patient population, 179 performed LP at baseline, with follow-up LP taken roughly 2.5 years later in 104 patients. Positron Emission Tomography (PET) scans were utilized to measure the Aß deposits in the brains of a subgroup of study participants. The PET scans revealed an uptick in amyloid levels.

The investigators found significant correlations between the longitudinal change in CSF Aß42 levels and baseline OSA severity over the 2 years. Although changes were not predictive of cognitive degeneration, the relationship was considered to be - most likely - nonlinear, and Osorio and colleagues suggested that other factors may influence the changes, such as tau pathology.

However, the use of biomarkers to identify these changes early on may be enough to make a difference. Osorio said that since no treatment exists for AD, the current state of thinking is that treatment is occurring too late, when brain damage is already widespread.

“There's the possibility that some of the drugs that we have discarded might work if we treat earlier in the disease process,” Osorio said. “Prior to clinical AD, there is an intermediate stage that we call Mild Cognitive Impairment, and before that there is a stage that we call preclinical AD. In preclinical AD, in which by definition there are no symptoms, there is already ongoing amyloid deposition and tau aggregates that can be detected using biomarkers, but only very incipient neurodegeneration, providing a critical opportunity for potential intervention with disease-modifying therapies. In this case, treatment of sleep disturbances.”

In a similar breadth, in October, the US Food and Drug Administration (FDA) approved a new sleep apnea device, the Remedē System, a device that stimulates diaphragm-signaling nerves in the chest which aides the breathing process. The FDA analyzed data involving 141 patients assessed on the AHI and found that after 6 months of treatment, about half of the patients had reported a reduction in AHI by 50% or more. While approved to treat central sleep apnea (CSA), the approval marks a notable step into addressing sleep-related issues.  

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