New research from the Washington University School of Medicine in St. Louis has found strong evidence that disruptions in sleep cycles could be an early, preclinical sign of Alzheimer's disease. A further companion study in mice found that circadian rhythm disruptions could directly accelerate the accumulation of amyloid plaques in the brain – the build-up of which are strongly linked to Alzheimer's disease and memory loss.

For some time, it has been understood that patients with Alzheimer's disease also suffer from broken sleep and disrupted circadian rhythms. In a newly published study, researchers set out to investigate if there was a correlation between broken sleep patterns and preclinical amyloid buildup in the brains of otherwise normal and healthy subjects.

The study followed 189 adults, with an average age of 66, and tested for the presence of amyloid proteins using positron emission tomography (PET) scans and cerebrospinal fluid testing. As well as completing a detailed sleep diary, the subjects all wore tracking devices designed to record movements day and night.

Fifty of the subjects had either abnormal brain scans or abnormal cerebrospinal fluid, and all 50 also noted significant circadian rhythm disruptions. After accounting for sleep apnea, age and sex, the correlations were still clearly identified.

"It wasn't that the people in the study were sleep-deprived," say Erik S. Musiek, first author on the study. "But their sleep tended to be fragmented. Sleeping for eight hours at night is very different from getting eight hours of sleep in one-hour increments during daytime naps."

The big question raised by the study is a classic chicken or the egg scenario. Does disrupted sleep cause a buildup of amyloid plaques in the brain, or is disrupted sleep simply a result of that amyloid buildup?

Previous research from the Washington University team has found that directly disrupting the sleep of healthy middle-aged subjects does cause an increase in amyloid beta levels. In fact, just one night of interrupted sleep was found to correlate with a 10 percent increase in amyloid beta levels.

Another more recent study from the team, published in the Journal of Experimental Medicine, examined how altering circadian rhythms in mice could affect the deposits of these amyloid plaques. The study used a mouse model in which the genes controlling the animals' circadian rhythms had been disabled.

"Over two months, mice with disrupted circadian rhythms developed considerably more amyloid plaques than mice with normal rhythms," says Musiek. "The mice also had changes in the normal, daily rhythms of amyloid protein in the brain. It's the first data demonstrating that the disruption of circadian rhythms could be accelerating the deposition of plaques."

The researchers suggest the strongest takeaway from the research at this stage is that sleep disruptions could act as clear biomarkers for preclinical stages of Alzheimer's disease. As the disease can often take 10 to 20 years of amyloid accumulation before clinically detectable symptoms occur, any early biomarkers can help physicians treat the disease before too much irreversible neurodegenerative damage takes place.

Following on from this work the Washington University team hopes to follow these human subjects over a longer span of time to see if Alzheimer's disease develops in those found to have disrupted sleep and early amyloid build up.

The new study was published in the journal JAMA Neurology.