Sleep cycle troubles may be early sign of Alzheimer’s disease


A fitful night’s sleep and a habit of daytime catnapping may be an early-warning sign of Alzheimer’s dementia, according to new research conducted in humans and mice.

Restless nights and sleepy days are a common pattern in patients with full-blown Alzheimer’s. Those disrupted circadian rhythms are a symptom that can upend the lives of caregivers and cause confusion and anxiety in patients.

Less dramatic levels of sleep disruption, including trouble falling asleep and more frequent nighttime wakening, are also typical as people age.


A new study finds that, in older people who show no signs of cognitive impairment, those with a sleep-wake cycle that is subtly off-kilter are more likely to have amyloid protein deposits in their brains. Those amyloid “plaques” are a hallmark of Alzheimer’s, and they can develop years before symptoms of memory loss or thinking problems are evident.

Study participants whose sleep patterns followed a clearer pattern of sleeping through the night and staying awake during the day were less likely to have significant clumps of amyloid protein in their brains, suggesting they were less likely to go on to develop Alzheimer’s disease.

The new research, published Monday by the journal JAMA Neurology, doesn’t answer the question of whether a messy sleep pattern actually contributes to the development of Alzheimer’s or is just a sign of the disorder.

If it’s merely a sign of impending Alzheimer’s, could still be a useful tell. Currently, the earliest clear signs of Alzheimer’s disease — those plaque deposits — can only be detected with sophisticated brain imaging. If physicians and researchers had a behavioral signpost that could be readily detected with a wearable activity monitor, they’d likely identify more people who could enroll in research studies, or who might benefit from early efforts to head off dementia.

On the other hand, if a sleep-wake cycle with frequent nighttime awakening and more daytime sleeping actually helps Alzheimer’s gain a foothold, that finding could be even more valuable: Patients with broken sleep patterns could be counseled to take steps to improve their nighttime sleep quality, perhaps delaying or preventing their progression toward dementia.

“I don’t want to scare people into thinking that if they wake up often at night they’ll have Alzheimer’s,” said study co-author Dr. Erik S. Musiek, a Washington University neurologist who studies the role of the circadian clock on aging.


Some changes in sleep are typical as people age. But while disrupted sleep patterns generally manifest themselves as nighttime awakenings and short bursts of compensating daytime sleep, participants didn’t always notice or report these occurrences, Musiek said.

“These are subtle things, and we can detect them in a large group of people,” he said.

The role that sleep disruption plays in early Alzheimer’s — whether it contributes to the disease or merely signals its presence — should become clearer as his research team tracks study participants into old age.

In the meantime, research conducted on mice offers a tantalizing peek at an answer, Musiek said. When scientists from Washington University and the University of Pennsylvania bred mice who whose normal circadian rhythms were completely knocked out by a combination of drugs and genetic engineering, amyloid plaques accumulated quickly in the hippocampus, a key structure in memory and learning.

Only later would the behavioral symptoms of Alzheimer’s appear.

That study, slated for publication in the Journal of Experimental Medicine, suggests that irregularities of circadian rhythm accelerate amyloid plaque accumulation in the brain and speed the appearance of Alzheimer’s more obvious symptoms — memory and thinking problems.

Whether that dynamic is repeated in humans remains to be shown.

In the research published Monday, 189 participants had an average age of close to 67 years when they enrolled in the study between 2010 and 2012. Each wore an activity monitor for seven to 14 days. The wearable device detected when and for how long a participant slept, how often she awakened at night, and when she appeared to be napping during the day.

The participants, both men and women, all were cognitively healthy at the time they enrolled, with no signs of mental impairment or memory problems.

Around the time they wore their activity-devices, 142 of the participants also had a specialized PET scan of the brain to detect amyloid deposits.

Some 26 of the study’s subjects showed amyloid deposits suggestive of very early Alzheimer’s disease, while 116 did not. On three of eight arcane measures of circadian function, the group with early Alzheimer’s scored higher than those shown to have no significant build-up of amyloid in their brains.

“A clear implication of our findings is that therapies directly targeting the circadian system to normalize circadian timing, rather than just augmenting total sleep, may be beneficial in the prevention of Alzheimer’s Disease,” the authors wrote.

Musiek said he recommends a range of practices to patients concerned about the prospect of dementia. They aren’t that different from the usual “sleep hygiene” practices that sleep-medicine specialists recommend for all patients.

“You want to consolidate your sleep as much as possible at night,” he said. “I always tell my patients not to use electronic devices at night, to sleep in a dark room — and to go to sleep, not watch TV in bed.”

Musiek also urges his patients to “get up in morning, get active, go out and get into the morning light.” Eating a good breakfast “helps synchronize your clock,” he added.

Finally, he said, our early-bird and night-owl inclinations often have their roots in our genes. We would do well to try to accommodate, not fight, those differences.

“People get into trouble trying to force themselves into a different mode,” Musiek said. “We should listen to our bodies, and try to understand our own rhythms, and keep day and night within that range.”

Twitter: @LATMelissaHealy


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