New research published in JAMA Neurology suggests that those people whose memory is intact and who do not show any signs of Alzheimer's can have disrupted circadian rhythms—which may be a very early sign of Alzheimer's.

One such study suggested that poor sleep may lead to brain proteins, such as amyloid beta and tau becoming tangled, a known hallmark of the neurological condition.

Another study suggested that sleep disorders may be an early sign of Alzheimer's disease, and although the study was observational, it found biological markers of the disease in the brains of people who reported insomnia or disrupted sleep.

Now, new research deepens our understanding of this complex relationship, as scientists find that disruptions in the sleep/wake cycle in completely asymptomatic people might signal the presence of preclinical evidence of Alzheimer's disease.

Dr. Erik S. Musiek—an assistant professor of neurology at the Washington University School of Medicine in St. Louis, MO—is the first author of the study.

The scientists were prompted in their new study by previous animal and human studies that were conducted at Washington University, which revealed that levels of the Alzheimer's-related brain protein amyloid beta go up and down at different times through the circadian rhythm. They also found that less sleep may lead to more amyloid beta in the brain.

They therefore set out to investigate circadian rhythms in seniors and checked their results by also carrying out a second study in mice. The findings are particularly significant given that Alzheimer's-related brain damage can occur up to 20 years before any symptoms start to show, so early detection is crucial.

Disrupted body clock linked with Alzheimer's

Dr. Musiek and colleagues used tracking devices and sleep diaries to track the sleep and circadian patterns of 189 participants who were aged 66, on average.

They underwent positron emission tomography scans, cerebral spinal fluid tests, or both to check for the presence of Alzheimer's-related brain proteins.

Of these people, 139 had no signs of Alzheimer's, and the majority of them had relatively normal circadian rhythms.

However, 50 participants whose brain scans and spinal fluid tests revealed some preclinical signs of Alzheimer's all had a disrupted sleep/wake cycle, which means that they rested more than normal during the day and less than normal during the night.

Overall, therefore, the people who had more disorderly circadian patterns—such as taking frequent naps during the day—were more likely to have preclinical signs of Alzheimer's.

"In this new study, we found that people with preclinical Alzheimer's disease had more fragmentation in their circadian activity patterns, with more periods of inactivity or sleep during the day and more periods of activity at night."

Study co-author Dr. Yo-El Ju, Washington University School of Medicine

"It wasn't that the people in the study were sleep-deprived," notes Dr. Musiek, "[b]ut their sleep tended to be fragmented. Sleeping for 8 hours at night is very different from getting 8 hours of sleep in 1-hour increments during daytime naps."

Causality remains unclear

The findings echo those of the mouse study published The Journal of Experimental Medicine. In it, mice were genetically engineered to have a dysfunctional circadian clock.

"Over 2 months, mice with disrupted circadian rhythms developed considerably more amyloid plaques than mice with normal rhythms," explains Dr. 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," he adds.

Still, the researchers also emphasize the fact that the findings are too preliminary to tell whether or not Alzheimer's causes body clock disruptions or vice versa. "At the very least, these disruptions in circadian rhythms may serve as a biomarker for preclinical disease," Dr. Ju says.