People with sleep-disordered breathing experience repeated episodes of hypopnea (under-breathing) and apnea (not breathing) during sleep. The most common form, obstructive sleep apnea, occurs in around 3 in 10 men and 1 in 5 women, according to the Alzheimer's Association.
It occurs when the upper airway closes fully or partially while efforts to breathe continue, and it can wake a person 50 or 60 times a night, interrupting the stages of sleep necessary for a restful night. It often starts in middle age, before clinical signs of Alzheimer's tend to appear.
In one study of 516 cognitively normal adults 71 to 78 years old, those with sleep-disordered breathing had greater increases in beta-amyloid deposits — one of the biomarkers — over a three-year period. This was true regardless of whether they had the APOE-e4 gene considered a risk factor for Alzheimer's.
A second study found that obstructive sleep apnea was associated with increases in amyloid buildup in older people with mild cognitive impairment (MCI), and a third found such an association in both normal and MCI subjects.
While correlation between sleep apnea and dementia has been documented in the past, these are among the first longitudinal studies to look at the relationship between sleep disruption and the biomarkers commonly associated with Alzheimer's disease, said Megan Hogan, one of the Wheaton researchers.
Noting that past research has found that the brain clears up deposits of amyloid plaque during sleep, Hogan hypothesized that apnea may impede this process.
"During sleep . . . your brain has time to wash away all the toxins that have built up throughout the day. Continually interrupting sleep may give it less time to do that," she said.
It may be in the deepest stages of sleep that the clearing-up takes place, said Ronald C. Petersen, director of the Mayo Clinic Alzheimer's Disease Research Center and the Mayo Clinic Study of Aging. "If you're only making it to Stage 1 or Stage 2, and then you start choking or snoring or whatever, and you wake yourself up and you do it again and again, you may not even be aware of it, but you . . . may be accumulating this bad amyloid in the brain rather than clearing it," he said.
In recent research, people repeatedly jolted awake during the night showed immediate increases in amyloid buildup, Petersen said. And if the sleep disruption continued for a couple of weeks, subjects showed increases in the tau protein tangles that also are associated with Alzheimer's.
Repeated deprivation of oxygen to the brain that occurs during apnea also may contribute to amyloid buildup, as oxygen regulates an enzyme that plays a role in creating amyloid, Hogan said.
It is not yet clear whether the relationship between apnea and dementia is causative — "whether people with very early levels of brain disease are having trouble sleeping, or whether people having trouble sleeping are more likely to develop brain disease," said Keith N. Fargo, director of scientific programs and outreach at the Alzheimer's Association. He noted that animal studies have suggested it could go both ways.
"Ultimately it doesn't matter what the direction is for this to have an effect on your life," he said. "If you're waking up your partner multiple times a night or you're tired all day, then you really, really need to go get checked by your doctor, because it could be a sign of something serious. Or if it's not, just treating the apnea could help with your day-to-day cognition."
A next step in confirming that sleep disruption causes amyloid buildup could be to conduct an intervention with CPAP machines and see if their use reduces the incidence of amyloid buildup, Hogan and Fargo said.