Bad Sleep Linked to Alzheimer's

Poor sleep appears to be associated with early signs of Alzheimer's disease.

Feb 15, 2012— -- Disturbed sleep is associated with preclinical signs of Alzheimer's disease, researchers found.

In a small cohort study in cognitively normal people, frequent awakenings and a habit of lying awake were linked to higher levels of markers of the brain plaques that are a hallmark of Alzheimer's disease, according to Yo-El Ju, MD, of Washington University School of Medicine in St. Louis, and colleagues.

The full study is slated for presentation at the annual meeting of the American Academy of Neurology in New Orleans in April, but some of the data were released early.

Ju and colleagues cautioned that it's not clear if there's a cause-and-effect relationship or, if there is, which way it runs. "Further research is needed to determine why this is happening and whether sleep changes may predict cognitive decline," Ju said in a statement.

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Alzheimer's disease begins long before there any symptoms, the researchers noted, but signs of the beta-amyloid plaques that build up in the brains of Alzheimer's patients can be detected in some cognitively normal people.

There is also evidence from animal studies that sleep disruption causes a build-up in those beta-amyloid markers, they said.

To investigate the link in humans, they turned to the Adult Children Study, a cohort of which half the members have a family history of Alzheimer's. For this analysis, 100 participants, ages 45 to 80, were given standardized assessments and shown to be cognitively normal.

Participants wore an actigraph for 14 days to measure sleep in an objective fashion; sleep diaries and questionnaires were used to gather subjective measures.

The researchers also measured levels of amyloid beta-42 in cerebrospinal fluid and looked for increased retention of Pittsburgh compound B during amyloid imaging by positron emission tomography -- 25% of participants had preclinical signs of Alzheimer's.

On average, participants spent about eight hours in bed, as measured by both actigraph results and subjective reports, but average sleep time on the actigraph was 6.5 hours (significantly shorter at P<0.05) because of brief awakenings during the night.

Those who woke up more than five times an hour were more likely to have abnormal biomarkers indicating amyloid pathology.

And more of those with low sleep efficiency – defined as sleep time divided by time in bed of less than 85% -- had such signs compared with those with high sleep efficiency.

Such research is critical for the study of Alzheimer's disease, commented Judy Willis, MD, an educator and neurologist in Santa Barbara, Calif., and a member of the neurology academy.

"Interventions, once the disease has progressed to symptomatic diagnosis, are limited," Willis told MedPage Today in an email, "and there is no cure or even strong support for any treatment that can reverse the development of amyloid plaques in humans once they form."

But it may be possible to intervene at an earlier stage, especially if it turns out the disordered sleep actually causes the amyloid pathology, Willis said.

"Studies finding correlation are inadequate to confirm causality," she noted, adding it's equally possible that disrupted sleep has a role in the development of the disease or that it's an early sign of a disease already developing.

But studies in mice have found that interfering with their sleep led to increases in amyloid pathology. Although mice do not get Alzheimer's, that finding suggests that improved sleep might be a pathway to better mental health.

Even if disrupted sleep is just a predictor, it could be useful in pointing people toward future clinical trials, Willis said.

Ju said longer studies following sleep over years will be needed to tease out the cause-and-effect relationship. "Our study lays the groundwork for investigating whether manipulating sleep is a possible strategy in the prevention or slowing of Alzheimer's disease," she said.