Sleep and Alzheimer’s disease

Researchers at the University of Toronto say a sleep disorder that causes people to act out their dreams is the best current predictor of brain diseases like Parkinson’s and some other forms of dementia.

“Rapid-eye-movement sleep behaviour disorder (RBD) is not just a precursor but also a critical warning sign of neurodegeneration that can lead to brain disease,” says associate professor and lead author John Peever.

“In fact, as many as 80 to 90 per cent of people with sleep behaviour disorder will develop a brain disease.”1

Sleep is disrupted in people who likely have early Alzheimer’s disease but do not yet have the memory loss or other cognitive problems characteristic of full-blown disease, researchers at Washington University School of Medicine in St. Louis reported in a recent issue of JAMA Neurology.

The finding confirms earlier observations by some of the same researchers. Those studies showed a link in mice between sleep loss and brain plaques, a hallmark of Alzheimer’s disease. Early evidence tentatively suggests the connection may work in both directions: Alzheimer’s plaques disrupt sleep, and lack of sleep promotes Alzheimer’s plaques.


Sleep problems are common in people who have symptomatic Alzheimer’s disease


Sleep problems are common in people who have symptomatic Alzheimer’s disease, but scientists recently have begun to suspect that they also may be an indicator of early disease.

Participants who had preclinical Alzheimer’s disease had poorer sleep efficiency (80.4 percent) than people without markers of Alzheimer’s (83.7 percent). On average, those with preclinical disease were in bed as long as other participants, but they spent less time asleep. They also napped more often.2

What role does sleep apnea play in Alzheimer’s disease? According to some research it could be significant.

Severe sleep apnea is associated with measures of delayed recall and executive function in cognitively healthy older adults. Although further study is needed, this evidence may provide further rationale for the treatment of sleep apnea in older adults. Moreover, the role of sleep apnea as a risk factor for cognitive disorders needs to be determined.3

A recent study looking at sleep-disordered breathing and markers for Alzheimer’s disease (AD) risk in cerebrospinal fluid (CSF) and neuroimaging adds to the growing body of research linking the two.

But this study also poses an interesting question: Could Alzheimer’s disease in its “preclinical stages” also lead to sleep-disordered breathing and explain the increased prevalence of sleep-disordered breathing in the elderly?

“It’s really a chicken and egg story,” said Ricardo S. Osorio, MD, a research assistant professor at NYU School of Medicine who led the study. “Our study did not determine the direction of the causality, and, in fact, didn’t uncover a significant association between the two, until we broke out the data on lean and obese patients.”

When the researchers did consider body mass, they found that lean patients (defined as having a body mass index25), with sleep-disordered breathing did possess several specific and non-specific biomarkers of AD risk.  Among obese patients (BMI >25), glucose hypometabolism was also found in the medial temporal lobe, but was not significant in other AD-vulnerable regions.

“We know that about 10 to 20 percent of middle-aged adults in the United States have SDB [defined as an apnea-hypopnea index greater than 5] and that the number jumps dramatically in those over the age of 65,” said Dr. Osorio, noting that studies put the percentage of people over the age of 65 with SDB between 30 and 60 percent. “We don’t know why it becomes so prevalent, but one factor may be that some of these patients are in the earliest preclinical stages of AD.”

According to Dr. Osorio, the biochemical harbingers of AD are present 15 to 20 years before any of its currently recognized symptoms become apparent.

The NYU study enrolled 68 cognitively normal elderly patients (mean age 71.4±5.6, range 64-87) who underwent two nights of home monitoring for SDB and were tested for at least one diagnostic indicator of AD.

Dr. Osorio and his colleagues are planning to test their hypothesis that very early stage preclinical AD brain injury that associates with these biomarkers can lead to SDB. They have proposed a two-year longitudinal study that would enroll 200 cognitively normal subjects, include AD biomarkers and treat those patients with moderate to severe SDB with continuous positive airway pressure, or CPAP, over time.

The purpose of the study would help determine the “direction” of causality between SDB and preclinical AD in elderly patients. After an initial assessment, the patients would be given CPAP to treat their sleep apnea. After six months, they would be evaluated again for biomarker evidence of AD.

“If the biomarkers change, it may indicate that SDB is causing AD,” explained Dr. Osorio. “If they don’t change, the probable conclusion is that these patients are going to develop AD with or without CPAP, and that AD may either be causing the apneas or may simply coexist with SDB as part of aging.”

Either way, Dr. Osorio believes the relationship between SDB and AD deserves further study.

“Sleep apnea skyrockets in the elderly, and this fact hasn’t been given the attention it deserves by the sleep world or the Alzheimer’s world,” Dr. Osorio said. “Sleep particularly suffers from an outmoded perception that it is an inactive physiological process, when, in reality, it is a very active part of the day for the brain.”

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1. Acting out dreams while asleep could be warning sign of brain disorder. University of Toronto

2. University of Washing at St. Louis Newsroom. Michael C. Purdy

3. Ju G, Yoon IY, Lee SD, Kim TH, Choe JY, Kim KW. Effects of sleep apnea syndrome on delayed memory anActing out dreams while asleep could be warning sign of brain disorderd executive function in elderly adults. J Am Geriatr Soc. 2012 Jun;60(6):1099-103. doi: 10.1111/j.1532-5415.2012.03961.x. Epub 2012 May 30.