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

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.

 

 

Other Sleep Disorders
Restless legs syndrome should also be considered among sleep disorders in the nursing home population. “Perhaps all the pacing that we see in the nursing home residents with Alzheimer’s disease might be a result of restless legs,” Dr. Ancoli-Israel suggested. She cited research by Kathy Richards, PhD, RN, and colleagues, who looked at probable RLS and sleep apnea in relation to agitation in older adults with dementia.

They found probable RLS in 24% of their community sample. Agitation was associated with severe cognitive impairment but low apnea. So “RLS may be something we might want to examine a little more carefully in these patients,” said Dr. Ancoli-Israel. “If you can’t make the diagnosis, it might not be such a bad idea to just go ahead and try treating it and see if the treatment can be used in a diagnostic fashion. You may see improvement in pacing and agitation in this group.”

Environment Plays a Role
Apart from physiologic factors, environment also has a great influence in poor sleep and poor circadian rhythms. “In the nursing home, we found that patients are exposed to very little light,” Dr. Ancoli-Israel reported. Her own group has done research showing that the median daily exposure to light above 1,000 lux in a nursing home population was one minute. And at night the reverse is often true—not enough darkness. “Not getting enough light during the day and getting too much light at night are contributing to the poor rhythms and fragmented sleep that we see in this population.”

Likewise, sound has also been shown to contribute to poor sleep in the nursing home setting. “Reminding the staff to speak quietly,” Dr. Ancoli-Israel suggested, “might in itself help patients sleep better at night.”

Research with bright light therapy has shown that it may slightly decrease agitative behavior, consolidate the sleep/wake cycle, and increase the strength of the rest/activity rhythm, “but none of these results in any of these studies has been really robust,” Dr. Ancoli-Israel said. Trials with melatonin also have yielded weak results.
The Next Steps
“Where do we go from here? I think we still need some very good randomized, controlled trials examining the efficacy of both pharmacologic and behavioral treatments on sleep and circadian rhythms in Alzheimer’s disease and … other neurodegenerative diseases. We need to look at combinations of treatments, and light, exercise, and sleeping pills, if necessary,” said Dr. Ancoli-Israel.

She also advocated treating related disorders such as sleep apnea and RLS. “We need to include mortality in our outcome measures—that’s an end point that’s important to look at,” Dr. Ancoli-Israel said. “And we need to perhaps start earlier in our treatments. Let’s not wait until the patients are severely demented. Let’s not wait until they are institutionalized. Perhaps if we intervene earlier with some of these behavioral or pharmacologic treatments we might be able to influence activity rhythms. We might be able to decrease the risk of cognitive impairment or at least slow down deterioration. If we could show in our epidemiologic studies poor rhythms in people at risk for developing MCI or dementia, then maybe we should be doing something to fix those rhythms before they get to that point.”

—Glenn S. Williams
References

Suggested Reading
Martin JL, Webber AP, Alam T, et al. Daytime sleeping, sleep disturbance, and circadian rhythms in the nursing home. Am J Geriatr Psychiatry. 2006;14(2):121-129.
Neikrug AB, Ancoli-Israel S. Sleep disturbances in nursing homes. J Nutr Health Aging. 2010;14(3):207-211.
Rose KM, Beck C, Tsai PF, et al. Sleep disturbances and nocturnal agitation behaviors in older adults with dementia. Sleep. 2011;34(6):779-786.
Westerberg CE, Lundgren EM, Florczak SM, et al. Sleep influences the severity of memory disruption in amnestic mild cognitive impairment: results from sleep self-assessment and continuous activity monitoring. Alzheimer Dis Assoc Disord. 2010; June 29 [Epub ahead of print].

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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.

 

 

Other Sleep Disorders
Restless legs syndrome should also be considered among sleep disorders in the nursing home population. “Perhaps all the pacing that we see in the nursing home residents with Alzheimer’s disease might be a result of restless legs,” Dr. Ancoli-Israel suggested. She cited research by Kathy Richards, PhD, RN, and colleagues, who looked at probable RLS and sleep apnea in relation to agitation in older adults with dementia.

They found probable RLS in 24% of their community sample. Agitation was associated with severe cognitive impairment but low apnea. So “RLS may be something we might want to examine a little more carefully in these patients,” said Dr. Ancoli-Israel. “If you can’t make the diagnosis, it might not be such a bad idea to just go ahead and try treating it and see if the treatment can be used in a diagnostic fashion. You may see improvement in pacing and agitation in this group.”

Environment Plays a Role
Apart from physiologic factors, environment also has a great influence in poor sleep and poor circadian rhythms. “In the nursing home, we found that patients are exposed to very little light,” Dr. Ancoli-Israel reported. Her own group has done research showing that the median daily exposure to light above 1,000 lux in a nursing home population was one minute. And at night the reverse is often true—not enough darkness. “Not getting enough light during the day and getting too much light at night are contributing to the poor rhythms and fragmented sleep that we see in this population.”

Likewise, sound has also been shown to contribute to poor sleep in the nursing home setting. “Reminding the staff to speak quietly,” Dr. Ancoli-Israel suggested, “might in itself help patients sleep better at night.”

Research with bright light therapy has shown that it may slightly decrease agitative behavior, consolidate the sleep/wake cycle, and increase the strength of the rest/activity rhythm, “but none of these results in any of these studies has been really robust,” Dr. Ancoli-Israel said. Trials with melatonin also have yielded weak results.
The Next Steps
“Where do we go from here? I think we still need some very good randomized, controlled trials examining the efficacy of both pharmacologic and behavioral treatments on sleep and circadian rhythms in Alzheimer’s disease and … other neurodegenerative diseases. We need to look at combinations of treatments, and light, exercise, and sleeping pills, if necessary,” said Dr. Ancoli-Israel.

She also advocated treating related disorders such as sleep apnea and RLS. “We need to include mortality in our outcome measures—that’s an end point that’s important to look at,” Dr. Ancoli-Israel said. “And we need to perhaps start earlier in our treatments. Let’s not wait until the patients are severely demented. Let’s not wait until they are institutionalized. Perhaps if we intervene earlier with some of these behavioral or pharmacologic treatments we might be able to influence activity rhythms. We might be able to decrease the risk of cognitive impairment or at least slow down deterioration. If we could show in our epidemiologic studies poor rhythms in people at risk for developing MCI or dementia, then maybe we should be doing something to fix those rhythms before they get to that point.”

—Glenn S. Williams

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.

 

 

Other Sleep Disorders
Restless legs syndrome should also be considered among sleep disorders in the nursing home population. “Perhaps all the pacing that we see in the nursing home residents with Alzheimer’s disease might be a result of restless legs,” Dr. Ancoli-Israel suggested. She cited research by Kathy Richards, PhD, RN, and colleagues, who looked at probable RLS and sleep apnea in relation to agitation in older adults with dementia.

They found probable RLS in 24% of their community sample. Agitation was associated with severe cognitive impairment but low apnea. So “RLS may be something we might want to examine a little more carefully in these patients,” said Dr. Ancoli-Israel. “If you can’t make the diagnosis, it might not be such a bad idea to just go ahead and try treating it and see if the treatment can be used in a diagnostic fashion. You may see improvement in pacing and agitation in this group.”

Environment Plays a Role
Apart from physiologic factors, environment also has a great influence in poor sleep and poor circadian rhythms. “In the nursing home, we found that patients are exposed to very little light,” Dr. Ancoli-Israel reported. Her own group has done research showing that the median daily exposure to light above 1,000 lux in a nursing home population was one minute. And at night the reverse is often true—not enough darkness. “Not getting enough light during the day and getting too much light at night are contributing to the poor rhythms and fragmented sleep that we see in this population.”

Likewise, sound has also been shown to contribute to poor sleep in the nursing home setting. “Reminding the staff to speak quietly,” Dr. Ancoli-Israel suggested, “might in itself help patients sleep better at night.”

Research with bright light therapy has shown that it may slightly decrease agitative behavior, consolidate the sleep/wake cycle, and increase the strength of the rest/activity rhythm, “but none of these results in any of these studies has been really robust,” Dr. Ancoli-Israel said. Trials with melatonin also have yielded weak results.
The Next Steps
“Where do we go from here? I think we still need some very good randomized, controlled trials examining the efficacy of both pharmacologic and behavioral treatments on sleep and circadian rhythms in Alzheimer’s disease and … other neurodegenerative diseases. We need to look at combinations of treatments, and light, exercise, and sleeping pills, if necessary,” said Dr. Ancoli-Israel.

She also advocated treating related disorders such as sleep apnea and RLS. “We need to include mortality in our outcome measures—that’s an end point that’s important to look at,” Dr. Ancoli-Israel said. “And we need to perhaps start earlier in our treatments. Let’s not wait until the patients are severely demented. Let’s not wait until they are institutionalized. Perhaps if we intervene earlier with some of these behavioral or pharmacologic treatments we might be able to influence activity rhythms. We might be able to decrease the risk of cognitive impairment or at least slow down deterioration. If we could show in our epidemiologic studies poor rhythms in people at risk for developing MCI or dementia, then maybe we should be doing something to fix those rhythms before they get to that point.”

—Glenn S. Williams
References

Suggested Reading
Martin JL, Webber AP, Alam T, et al. Daytime sleeping, sleep disturbance, and circadian rhythms in the nursing home. Am J Geriatr Psychiatry. 2006;14(2):121-129.
Neikrug AB, Ancoli-Israel S. Sleep disturbances in nursing homes. J Nutr Health Aging. 2010;14(3):207-211.
Rose KM, Beck C, Tsai PF, et al. Sleep disturbances and nocturnal agitation behaviors in older adults with dementia. Sleep. 2011;34(6):779-786.
Westerberg CE, Lundgren EM, Florczak SM, et al. Sleep influences the severity of memory disruption in amnestic mild cognitive impairment: results from sleep self-assessment and continuous activity monitoring. Alzheimer Dis Assoc Disord. 2010; June 29 [Epub ahead of print].

References

Suggested Reading
Martin JL, Webber AP, Alam T, et al. Daytime sleeping, sleep disturbance, and circadian rhythms in the nursing home. Am J Geriatr Psychiatry. 2006;14(2):121-129.
Neikrug AB, Ancoli-Israel S. Sleep disturbances in nursing homes. J Nutr Health Aging. 2010;14(3):207-211.
Rose KM, Beck C, Tsai PF, et al. Sleep disturbances and nocturnal agitation behaviors in older adults with dementia. Sleep. 2011;34(6):779-786.
Westerberg CE, Lundgren EM, Florczak SM, et al. Sleep influences the severity of memory disruption in amnestic mild cognitive impairment: results from sleep self-assessment and continuous activity monitoring. Alzheimer Dis Assoc Disord. 2010; June 29 [Epub ahead of print].

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