February 6, 2018

Fractured Sleep, Fractured Mind

Which comes first: sleep problems or the accumulation of proteins related to Alzheimer's?

Your regular sleep-wake cycle — the time you normally go to bed and when you wake up — is a big part of the daily patterns that make up the body's clock or circadian rhythms.

Disruptions in sleep patterns seem to be linked to certain mental health disorders, like depression, but they are also thought to be a potential sign of more serious problems such as Alzheimer’s disease. A new study confirms this connection, though it’s still not exactly clear which comes first, the sleep changes or the brain changes.

“[P]eople 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.”

Researchers had 190 participants, average age 66, undergo brain scans, spinal fluid testing or both, to measure amyloid beta, a main protein that accumulates in the plaques seen in Alzheimer’s disease. People participating in the study also kept sleep diaries to chronicle their sleep patterns, and wore devices that monitored their movements throughout the day and night, to confirm when they were sleeping or awake.

The results were striking: About 140 of the participants had normal levels of amyloid beta and the majority of this group didn’t have many sleep problems. Some did have sleep apnea, or certain sleep problems due to being on the older end of the spectrum, but nothing outstanding.

All of the 50 participants who did have higher levels of amyloid beta had some sleep problems, including higher levels of activity at night or more periods of sleep during the day. This was true even taking into account variables that might affect activity/sleep like sleep apnea and age.

“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,” said study author, Yo-El Ju, in a statement.

Meanwhile, the Washington University School of Medicine team conducted another experiment, this one with mice. Using genetic engineering, they knocked out a gene that controls circadian rhythm, so the mice’s sleep patterns were disrupted. These mice, compared to normal controls, had more accumulation of amyloid beta in their brains over time, the researchers found.

The brain does its housekeeping during sleep. This is when it clears out biological waste products such as the proteins related to Alzheimer’s. But even with these two new studies, it’s not totally clear which comes first: the sleep problems or other brain changes related to Alzheimer’s.

The results do suggest that changes in sleep patterns may at least be a possible early marker for Alzheimer’s disease to come. The team plans to follow up with the participants to see who develops full-blown Alzheimer’s disease over time.

It’s important to remember that not everyone with Alzheimer’s-related proteins in their brains will develop major symptoms. And it’s also worth pointing out that not everyone with sleep problems will develop dementia — millions of people have insomnia or other sleep problems, and they aren't necessarily an early marker of brain disease. So don’t worry too much if you have trouble sleeping every now and then.

The results may eventually help doctors diagnose the disease or at least know who’s at greater risk in the future. And it’s certainly a reminder to take sleep seriously and not let it be the first thing we sacrifice when life gets busy.

The human study is published in JAMA Neurology; the mouse study is published in The Journal of Experimental Medicine.

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