Poor sleep and the risk of dementia go hand in hand, but no one knew which came first. In what researchers say is the first study of its kind, a study published Monday in the journal JAMA Neurology shows that excessive daytime sleepiness in cognitively normal elderly leads to a buildup of a plaque in the brain called amyloid.
Depositing amyloid in brain tissue is the first known preclinical stage of Alzheimer’s and happens well before any obvious symptoms of dementia begin.
“We know that sleep is necessary to clear toxins and beta-amyloid in the brain,” said study author Prashanthi Vemuri, a research faculty member at the Mayo Clinic, where the study was done. “We also know that beta-amyloid causes sleep disruptions. So, it’s been a chicken and an egg problem.
“In our study, we wanted to know if excessive daytime sleepiness causes an increase of amyloid over time in people without dementia,” Vemuri continued. “And the answer was yes.”
“While further research is necessary, this study adds a new question that doctors can ask patients to assess risk and potentially intervene, said Dr. Richard Isaacson, Director of the Alzheimer’s Prevention Clinic at Weill Cornell Medicine and NewYork-Presbyterian, who was not involved in the study.
“In fact, the findings will change the way i care for patients,” said Isaacson, “as i will now proactively ask about excessive daytime sleepiness as one of the many potentially modifiable risk factors for the disease.”
The Mayo researchers reached out to people 70 and older who were enrolled in the Mayo Clinic Study of Aging, a population-based sample in Olmsted County, Minnesota. To be included in the study, participants had to have baseline scan and a later scan of their brains on file, complete a sleep quality questionnaire and be certified free of dementia by a team of specialists who administered a battery of cognitive tests.
That process whittled down the initial sample of 2,172 to 283 people with an average age of 77. Researchers measured the amount of beta-amyloid buildup in their brains over time, and compared those results to the amount of daytime sleepiness each person reported.
Subjects who were most drowsy during the day were found to have greater amounts of Alzheimer’s-causing amyloids over the two-year period of the study, especially in the areas of the brain responsible for emotion, memory retrieval and behavior.
In an editorial that accompanied the study, sleep researchers Bryce Mander of the University of California, Irvine and Joseph Winer of the University of California, Berkeley said the study was the first to directly addresses the relationship over time of poor sleep and biomarkers for developing Alzheimer’s.
“What we’re excited about is that it’s the first to show longitudinal evidence in humans,” Winer said in an interview. “Most of our evidence has come from mice studies and looking at people at one time point. This is the first study that followed people over time.”
Dr. Yo-El Ju, a neurologist at the Washington University School of Medicine, agreed.
“Importantly, it is the first longitudinal study of the relationship between sleep and Alzheimer’s Disease in the preclinical stage, meaning before any cognitive changes appear,” said Ju. “This finding is important because it means we could potentially treat sleep problems to reduce risk of AD years down the road.”
However, the study was not able to determine what type of sleep disruption — such as insomnia, obstructive sleep apnea or restless legs syndrome — was the cause of the daytime fatigue.
The study was not able to answer the role of sleep stages, the extent of the damage that poor sleep might cause, nor “the extent to which treatment of OSA (obstructive sleep apnea) or other disorders or increased sleep duration can slow down amyloid accumulation and cognitive decline,” said Dr. Eric Reiman, executive director of the Banner Alzheimer’s Institute, who was not involved in the study. He hopes future research will tackle those and other questions.
Sleep and dementia research
Study after study has shown a link between fragmented sleep and the risk for cognitive decline.
A 2017 study found that people who get less REM, or dream-stage, sleep may be at higher risk for dementia. REM is the fifth stage of sleep, when the eyes move, the body heats up, breathing and pulse quicken and the mind dreams.
A separate 2017 study in the journal Neurology looked at the relationship between sleep quality and levels of various proteins and inflammatory markers in the cerebrospinal fluid of 101 cognitively healthy adults with an average age of 63. All participants had known risk factors for Alzheimer’s, such as family history or evidence of the APOE gene, which is associated with a greater chance of developing the disease.
“Our findings align with the idea that worse sleep may contribute to the accumulation of Alzheimer’s-related proteins in the brain,” said study co-author Barbara Bendlin of the Wisconsin Alzheimer’s Disease Research Center. “The fact that we can find these effects in people who are cognitively healthy and close to middle age suggest that these relationships appear early, perhaps providing a window of opportunity for intervention.”
Yet another study, published last year in the journal Brain, found that healthy middle-age adults who slept badly for just one night produced an abundance of beta-amyloid, according to study author Dr. Yo-El Ju, an assistant professor of neurology at Washington University’s Sleep Medicine Center.
She also found that a week of disrupted sleep increased the amount of tau, another protein responsible for the tangles associated with Alzheimer’s, frontal lobe dementia and Lewy body disease.
“Overall, these studies confirms the relationship between early Alzheimer’s disease and sleep disturbance,” said Dr. Yo-El Ju. “They expand — in terms of both time and symptoms — the window in which sleep-wake problems can be assessed for and treated, with the hope of reducing the risk of dementia due to Alzheimer’s disease.”
A sleep-deprived nation
The connection between sleep and dementia is especially worrisome, experts say, due to the sleep habits of Americans and people around the world.
According to the World Sleep Society, sleep deprivation is threatening the health of up to 45% of the world’s population.
Depending on our age, we are supposed to get between seven and 10 hours of sleep each night.
But according to the US Centers for Disease Control and Prevention, one in three Americans don’t get enough sleep. In addition, 50 million to 70 million Americans struggle with sleep disorders such as sleep apnea, insomnia and restless leg syndrome, which can ruin a good night’s shuteye.
The CDC calls that a “public health problem,” because disrupted sleep is associated with a higher risk of conditions including diabetes, stroke and cardiovascular disease.