Article

Sleep/Wake Disruption and Circadian Rhythm Disturbance in Alzheimer's Disease


 

References

Among patients with Alzheimer’s disease or mild cognitive impairment, sleep disorders and abnormal circadian rhythms are common—but too often overlooked—problems that may have significant consequences.

MINNEAPOLIS—In most nursing homes, this is a pretty typical picture—the residents are sitting around and no matter what time of day or night it is, no matter where they are sitting, they are sound asleep. They briefly wake up, and then they are sound asleep again.

“The sleep/wake rhythm in this population is really a 24-hour problem,” said Sonia Ancoli-Israel, PhD, at the 25th Anniversary Meeting of the Associated Professional Sleep Societies. It is characterized by a lack of a defined sleep/wake cycle, as residents spend much of the day napping.

Dr. Ancoli-Israel, Professor of Psychiatry at the University of California, San Diego, calls this “wake fragmentation.” The residents have sleep fragmentation at night and wake fragmentation during the day. “What you see in a good sleep/wake activity rhythm is good strong activity during the day and very little activity at night,” she said. But for many nursing home residents with dementia, what is seen instead is very disrupted and disturbed sleep. Based solely on their sleep/wake activity rhythms, it would be difficult to tease out what time of day it was, because day and night look so similar.

“Essentially, these Alzheimer’s patients are never asleep for a full hour, and they are never awake for a full hour throughout the 24-hour day,” said Dr. Ancoli-Israel. The times of greatest alertness, she said, are usually breakfast, lunch, and dinner.

Dr. Ancoli-Israel cited one study in which Jennifer L. Martin, PhD, and colleagues found that among 492 nursing home residents, 69% experienced daytime sleeping, 60% had disturbed nighttime sleep, and 97% had abnormal circadian rhythms. The researchers also found that more daytime sleep and less nighttime sleep were associated with weaker circadian activity rhythms.

The Consequences of Not Sleeping Well
“There are consequences to not sleeping well, and there are consequences to disrupted rhythms in this population,” said Dr. Ancoli-Israel. In older adults, sleep disturbance—particularly nighttime insomnia—is a risk factor for mortality. For daytime sleepiness the risk is 1.5 times higher than that for normal older adults, and for sleep-onset delay (difficulty falling asleep) there is almost twice the risk of mortality. “So not sleeping well in nursing home patients is perhaps a sign of shorter survival.”

When Dr. Ancoli-Israel and colleagues compared their nursing home data with data collected from normal older adults, they found that patients with Alzheimer’s disease who had greater acrophase deviation—that is, the peak of their rhythm deviated on either side of the normal—had a higher risk of mortality. In a large study of community-dwelling women, at five-year follow-up those women with weaker circadian rhythm had a higher likelihood of developing MCI or dementia. A similar increased risk was seen in women with more phase delay.

Sleep Apnea and Dementia
“Sleep apnea is very common in older adults, but it is even more common in older adults who have dementia,” said Dr. Ancoli-Israel. Years ago, she and her colleagues showed that 90% of nursing home patients had at least five respiratory events per hour during sleep, with a mean apnea-hypopnea index (AHI) of 32. Just over 60% had an AHI of 15, and about half had an AHI greater than 20. “Sleep apnea is very common and can get quite severe in these nursing home patients with Alzheimer’s disease,” Dr. Ancoli-Israel said. In studying this association further, she and her colleagues found that those with more severe apnea were also more severely demented, and, similarly, those with severe dementia also had more severe sleep apnea. “There’s clearly a relationship between sleep apnea and dementia as well as circadian rhythms and dementia,” Dr. Ancoli-Israel said.

Next, Dr. Ancoli-Israel’s group looked at the cognitive effect of treating sleep apnea in patients with mild to moderate Alzheimer’s disease who were living at home with a caregiver. “We found that, first of all, they were able to tolerate continuous positive airway pressure (CPAP),” she said. “They wore the CPAP for about five hours per night—which is not that much less than many clinic patients wear it—and it clearly improved the sleep apnea, it improved their daytime sleepiness, it improved their nighttime sleep, and the most important part was that it improved some aspects of their cognitive functioning. And the caregivers also reported improvement not only in the patients but also in themselves. Their spouses with dementia were sleeping better, and they themselves were also sleeping better.”

The researchers then followed a small number of these patients. At six-month follow-up, those patients with Alzheimer’s disease who continued using CPAP showed less cognitive deterioration, less depression, and less daytime sleepiness, and they reported better sleep quality. “We’re not curing Alzheimer’s disease here, but we may be able to slow down the deterioration, and if that means that we can postpone institutionalization, then that would be a tremendous step forward in the field,” Dr. Ancoli-Israel commented.

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