Background

Continuous Positive Airway Pressure (CPAP) is an approved treatment using a machine and nasal mask to deliver continuous air flow and help keep the airways open during sleep. Sleep-disordered breathing and obstructive sleep apnea cause sleep fragmentation and nighttime hypoxia. People with Alzheimer’s have high rates of insomnia and other sleep disorders (e.g., Cooke et al., 2006). Beyond making them sleepy during the day, these sleep disorders are thought to worsen their cognitive impairment. Sleep-disordered breathing has been linked to cerebrospinal fluid and brain-imaging biomarker changes that predict Alzheimer's dementia, raising the question of whether hypoxia-inducing sleep disorders are a contributor to or a consequence of AD pathogenesis (Osorio et al., 2014; Osorio et al., 2014; Daulatzai 2013). In general, human and animal model research is implicating sleep more broadly in the pathogenesis of Alzheimer's disease (e.g., May 2014 conference story; Aug 2012 conference story).  

CPAP is standard treatment for sleep-disordered breathing and sleep apnea. The rationale of testing CPAP at various stages of Alzheimer’s disease is twofold: to test whether continuous brain oxygenation during sleep delays the deterioration of memory and other existing symptoms of Alzheimer’s and related dementias, and to see whether improving brain oxygenation during sleep might even have a mechanistic effect on the underlying neurodegeneration. 

Findings

In the early 2000s, a controlled, randomized trial at the University of California, San Diego, tested a three- and a six-week course of CPAP in 52 people with mild to moderate Alzheimer’s and obstructive sleep apnea. The primary outcomes were sleep quality and daytime sleepiness as reported by patient and caregiver, and cognitive function. Published results from this trial indicated improvements in certain aspects of cognition, but were underpowered to make definitive statements. This study contacted participants a year later and compared five patients who continued to use CPAP to five others who did not. The report on this follow-up indicated a larger cognitive improvement for continued CPAP users but clearly noted insufficient power and other limitations (Chong et al., 2006; Ancoli-Israel, 2008; Cooke et al., 2009; Richards 2009). These papers sparked interest in further clinical exploration of CPAP to address sleep quality as a potentially treatable factor in cognitive impairment in AD. 

In 2010, a single-center trial in Saint-Etienne, France, started evaluating a four-month course of CPAP in 100 people with mild to moderate Alzheimer's. This trial measures the effect of nightly CPAP on cognition using Behavioral Assessment of Dysexecutive Syndrome (BADS) zoo map scores; its secondary measures are rate of sleep apnea, neuropsychological tests, and a quality-of-life questionnaire. The study is set to be completed in spring 2015.

In 2012, a trial at three sites evaluated a six-month course of CPAP in 110 people with mild cognitive impairment. Primary outcome measures include several memory-test and other cognitive assessments. Secondary outcome measures include eight additional cognitive, clinical, and functional measures widely used in Alzheimer's trials, as well as three neuroimaging measures. This trial was to conclude in 2014 but results have not been announced. 

In July 2013, a small, open-label prevention trial started up at New York University. It will enroll an estimated 45 cognitively normal people aged 50 and older who have sleep-disordered breathing. Some will be offered a six-month course of CPAP; those who decline CPAP or do not comply with the CPAP regimen will be considered controls. The trial's primary outcome measures are CSF tau and Aβ42 levels, as well as two MRI measures, hippocampal volume, and cerebral vasoreactivity to CO2 challenge. The trial has an interventional component that measures these outcomes, as well as some memory functions, again after six months of CPAP treatment, and an observational component that revisits these measures at a two-year longitudinal followup. This trial is set to run until July 2017.

For all clinical trials of CPAP in Alzheimer's, see clinicaltrials.gov.