Poor sleep and daytime dozing may be an early sign of Alzheimer's disease
Circadian dysfunction may indicate early stage for Alzheimer's Disease
The research is published JAN.29 in the Journal JAMA Neurology
People with Alzheimer's disease are known to experience disturbances in internal body clocks, which affect the sleep-awake cycle and may increase the risk of developing a disorder. Alzheimer’s is characterized by amyloid plaques, initial interactions between beta-amyloid and nerve cells can lead to toxicity. Some studies suggest that the toxic effects of beta-amyloid occur before the formation of plaques and oligomers.
Recently, a new study that was conducted at the University of Washington Medical School in St. Louis showed that such circadian dysfunction occurs much earlier in individuals whose memories are intact, but whose brain scans indicate early, preclinical indications of Alzheimer's disease.
Research findings could potentially help doctors identify earlier people at risk from Alzheimer's Disease. This is important because the damage to Alzheimer's disease is likely to begin 15 to 20 years before the clinical symptoms occur. The development of amyloid plaques in the brain has been associated with Alzheimer's disease.
Sleep and circadian problems are very common in Alzheimer disease (AD)
The research was published on January 29th, 2018, in JAMA Neurology. "It wasn't the people in the study were sleep-deprived. But their sleep tended to be fragmented," said Erik S. Musiek, MD, PhD, assistant professor of neuroscience. "Sleeping for 8 hours at night is very different from getting those 8 hours of sleep in 1-hour increments during daytime naps."
The researchers also conducted a separate study in mice, published on 30th January 2018 in The Journal of Experimental Medicine, which shows that similar circadian disruptions speeded up the development of the beta-amyloid plaques, that have been linked to Alzheimer's disease.
Previous studies at the University of Washington, conducted in humans and animals, have found that amyloid levels fluctuate in predictable ways during the day and at night.
According to the study, amyloid levels of the protein fluctuate fall during sleep and rise when sleep this is interrupted or when people do not get enough deep sleep.
"In this new study we found that people with pre-clinical Alzheimer's disease had more dislocation in their normal activities, with more periods of inactivity or sleep during the day and more periods of nighttime activity," said Ju, a neuroscience professor.
Researchers followed circadian rhythms in 189, mentally normal, elderly adults with an average age of 66 years. Some people did (PET scans) to look for amyloid plaques associated with Alzheimer's in their brains. In others, they had examined their cerebrospinal fluid for Alzheimer-associated proteins, while some had scans and spinal fluid tests.
Out of all participants, 139 had no sign of amyloid proteins associated with preclinical Alzheimer’s, though several had circadian disruptions that were linked to advanced age, sleep apnea or other causes.
However, among the remaining 50 individuals (who either had abnormal cerebral tests or abnormal cerebrospinal fluid), all of them without exception experienced significant disturbances in the internal body clocks, determined by the duration and quality of rest achieved and activity during the day.
The sleep/wake cycle disorders remained, even after having been statistically tested for sleep apnea, age, and other factors.
Study subjects, from Washington University's Disease Control Center, all wore devices similar to "exercise trackers" for one to two weeks. Everyone also completed a detailed sleeping calendar every morning. By monitoring activity throughout the day and night, the researchers could assess how "scattered" was resting and activity within a 24-hour period.
People who had short intervals of activity and daytime and nighttime rest were more likely to have evidence of amyloid accumulation in their brains. These findings in humans were enhanced by research in mice.
In this study, in collaboration with Geraldine J. Kress, PhD, assistant professor of neuroscience, Dr. Musiek studied circadian rhythm disorders in Alzheimer's in mice. To disrupt circadian animal rhythms, the team of scientists suspended genes that control circadian clocks. "Over two months, those mice with disturbed circadian rhythms developed significantly more amyloid plaques than mice at normal rates," Dr. Musiek said. "Mice also had changes in the normal daily rhythms of amyloid protein in the brain."
It is the first evidence that interruption of circadian rhythms can accelerate the deposition of plaques.
Both Dr. Musiek and Dr. Ju have stated that it is too early to answer the question of whether disturbed circadian rhythms put people at risk for Alzheimer's disease or whether Alzheimer's disease related changes in the brain disrupt their circadian rhythms.
"At the very least, these disruptions in circadian rhythms may serve as a biomarker for preclinical disease," Dr. Ju said. "We want to bring back these subjects in the future to learn more about whether their sleep and circadian rhythm problems lead to increased Alzheimer's risk or whether the Alzheimer's disease brain changes cause sleep/wake cycle and circadian problems."