Research 5 min read

Secrets of Sleep in Alzheimer’s Disease

Intense disruptions to the circadian clock may impact how the disease develops.

By Abigail Fagan featured image Rawpixel /Getty Images

Doctors have long observed that people with Alzheimer’s disease have strange sleep patterns. They may get a burst of energy in the evening when the rest of the family is getting ready for bed. They may wake up repeatedly throughout the night and then take a string of naps throughout the day. Scientists previously attributed this unusual trait to the overall degeneration taking place in the brain, but now researchers are investigating the connection more closely.

A team from Washington University in St. Louis recently explored the relationship between circadian disruption and Alzheimer’s in two separate studies. They found evidence that a buildup of amyloid proteins in the brain — one of the hallmarks of Alzheimer’s disease — occurs when the circadian clock is off-kilter, even in adults with healthy memories. And while the findings don’t answer the question of whether circadian disruptions are a cause or effect of Alzheimer’s, they could be a useful indicator of the disease.

“Circadian dysfunction happens very early in the course of Alzheimer’s disease, and it may play a role in the disease progression,” says Erik Musiek, an assistant professor of neurology at the Washington University School of Medicine in St. Louis and an author on both studies.

For the first study, published in the journal JAMA Neurology, Musiek and his team collected sleep cycle data from 189 people over the age of 45 who showed no other signs of cognitive impairment. The participants wore a movement-tracking wristwatch and recorded the time they woke up and went to sleep for two weeks. The participants were also tested for “preclinical Alzheimer’s,” a period in which a person has no noticeable clinical symptoms, such as memory loss or confusion, but the brain shows some changes and biological markers of the disease. Musiek and his team checked for these biological markers, using an imaging technique called positron emission tomography, a spinal tap, or both within three years of gathering the person’s sleep data.

Most of the study participants had relatively normal sleep cycles and had no amyloid buildup. But the researchers found that the 50 people with preclinical Alzheimer’s all had more fragmented sleep rhythms than those with no sign of the disease.

That doesn’t mean that people should assume they have Alzheimer’s disease if they don’t sleep well, Musiek says. Sleep disruptions naturally increase with age, but the disruptions that correlated with preclinical Alzheimer’s were especially severe.

In a second study, published in the Journal of Experimental Medicine, the researchers also genetically disrupted the circadian rhythms in mice to see if they developed similar signs of Alzheimer’s. The mice constantly bounced between sleep and wake instead of resting for a substantial period of time. And after four months, the genetically modified mice had more amyloid plaques than typical mice.

The second study clearly demonstrates that severe changes to the circadian clock are linked to the accumulation of amyloid proteins, says Andrew Lim, an assistant professor of neurology at the University of Toronto and a neurologist at Sunnybrook Health Sciences Centre, who was not associated with the study.

But the studies don’t explain exactly how messy sleep patterns and Alzheimer’s are connected. “It really leaves open the question of whether these changes in sleep and circadian behavior are a manifestation of the Alzheimer’s disease pathology or whether they actually contribute to the development of the Alzheimer’s disease pathology,” Lim says.

It’s also uncertain whether the 50 individuals with preclinical Alzheimer’s will go on to receive a definitive diagnosis of the disease, says Clifford Saper, chairman of the department of neurology at Beth Israel Deaconess Medical Center and a professor of neurology and neuroscience at Harvard Medical School, who was not involved with the study. That’s because cognitive decline doesn’t usually start occurring until years or sometimes decades after preclinical signs appear.

But any links to circadian disruption are still critical for Alzheimer’s researchers to study. The disease has no cure, so sleep is a domain that scientists can target, control, and change. And normalizing sleep patterns could lead to better care, Saper says.

“It’s a huge problem,” Saper says. “If you had some sort of remedy that would allow people with Alzheimer’s disease to sleep eight hours of nice consolidated sleep between 11 p.m. and 7 a.m., you could potentially make it a lot easier to take care of them.”

Right now, when a loved one with Alzheimer’s begins to wander off at night, the family often institutionalizes them, Saper says. A regular sleep pattern could help them remain at home longer. And for those in specialized care centers, it could prevent nurses from sometimes sedating patients who are active at night. The drugs lead patients to feel groggy the next day, which can make their dementia appear worse, Saper says.

Musiek also hopes that doctors can eventually use a circadian rhythm test to identify how far along people are in the course of the disease. While positron emission tomography scans and spinal taps are fairly accurate, more affordable and less invasive alternatives would be even better, he says. Many researchers are working on developing similar early tests for the disease — from blood tests to cognitive assessments — with the goal of identifying the turning point when accumulating amyloid proteins starts causing memory loss.

“It’s one of the great mysteries of the disease, how you can walk around with a brain full of amyloid plaques for 10 or 15 years and be totally fine, and then all of a sudden things go downhill. If we can predict when that’s going to happen, it would be very useful,” Musiek says.