Less REM Sleep Tied to Higher Mortality

Erik Greb

July 14, 2020

Less rapid eye movement (REM) sleep is associated with an increased risk for death in middle-aged and older adults, new research suggests.

Investigators at the University of California, San Diego, found that over a 12-year period, each 5% reduction in REM sleep was associated with a 13% increase in mortality rate. However, the investigators note that this is only an association and does not indicate cause and effect.

Dr Sonia Ancoli-Israel

"Determining causality can be difficult," study investigator Sonia Ancoli-Israel, PhD, professor emeritus of psychiatry at the University of California, San Diego, told Medscape Medical News.

"It is therefore important that physicians and the public understand that our findings suggest an increased risk, but that does not mean that reduced REM will always result in shorter survival. With all the self-monitoring sleep gadgets available to the public, I would caution against any panic if one notices reduced REM. But mentioning it to a physician may be a clue to examine what else might be going on with that patient that could more easily be targeted," Ancoli-Israel added.

The research was published online July 6 in JAMA Neurology.

Negative Consequences

Approximately 50 to 70 million Americans have problems with sleep. Such problems have a multitude of consequences for health, including cardiovascular disease; metabolic, psychiatric, and cognitive disorders; lower quality of life; and increased mortality.

The investigators note that the aspects of sleep that may be driving this association remain unclear. Because decreased REM sleep has been associated with poor mental and physical health outcomes, the researchers hypothesized that decreased REM sleep may be associated with an increased risk for death.

To test this hypothesis, they conducted a multicenter population-based cross-sectional investigation using data from independent cohorts ― the Outcomes of Sleep Disorders in Older Men (MrOS) Sleep Study, and the Wisconsin Sleep Cohort (WSC).

The MrOS cohort included 2675 men (mean age, 76.3 years) who were recruited from December 2003 to March 2005 at six US centers and were followed for a median of 12.1 years.

The WSC cohort included 1386 individuals (54.3% men, mean age 51.5 years) and had a median follow-up of 20.8 years. Data from this study were used to replicate the findings from the MrOS study.

Primary outcome measures included all-cause and cause-specific mortality, which were confirmed using death certificates.

Participants in both cohorts underwent polysomnography and evaluation with the Epworth Sleepiness Scale. For MrOS participants, investigators calculated the total number of minutes per night spent in REM sleep and the corresponding percentage of total sleep time.

Less Sleep, More Death

Self-report sleep measures in MrOS participants were collected using the Pittsburgh Sleep Quality Index and the Functional Outcomes of Sleep Questionnaire

The investigators contacted participants in MrOS every 4 months to determine vital status. Cause of death was categorized by the International Classification of Diseases, Ninth Revision, as cardiovascular, cancer, and other.

In WSC, the researchers identified deaths by matching participants' social security numbers with national and state registries. The cause of death was categorized in the same manner as in the MrOS cohort.

Approximately half (53%) of the MrOS cohort died during follow-up. For each mortality category, the highest percentage of deaths occurred among those in the lowest quartile percentage of REM sleep.

Adjusted analyses revealed that the MrOS participants had a 13% higher mortality rate for every 5% reduction in REM sleep (hazard ratio [HR] 1.13; 95% CI, 1.08 – 1.19). These findings were similar for cardiovascular and other causes of death but were not significant for cancer-related mortality.

For all mortality categories, the mortality rate was higher for participants who had less than 15% REM sleep per night in comparison with individuals who had 15% or more.

The findings were similar in the WSC cohort despite its younger age, the inclusion of women, and longer follow-up (HR, 1.13; 95% CI, 1.08 – 1.19). Compared with MrOS participants, WSC participants were more likely to be obese and to use more antidepressants or sedatives.

Overall, the mean percentage of REM sleep was 19.2%. Participants in the lowest quartile of REM sleep generally were older, had higher rates of antidepressant use, hypertension, heart attack, and transient ischemic attack, and engaged in less physical activity.

Ask About Sleep

When the data were stratified by sex, the association between decreased REM sleep and mortality was significant for women but not for men.

Dr Susan Redline

"Obtaining a sleep study, representative of the patient's usual sleep, that shows reduced REM time should alert the neurologist to look for reasons for low REM," the study's co-investigator, Susan Redline, MD, MPH, Peter C. Farrell Professor of Sleep Medicine at Harvard Medical School in Boston, Massachusetts, told Medscape Medical News.

Redline added that measures to promote sleep health, such as encouraging regular, sufficient nightly sleep; offering guidance on avoiding alcohol before bedtime and on other healthy sleep practices; and treating sleep disorders may be beneficial.

Low REM time, especially interpreted with other relevant clinical information, may alert the neurologist that a patient may have risk factors for poorer health, she added.

Sleep studies are expensive and are in high demand, so "the most realistic approach is for the neurologist to be asking each and every patient about their sleep," said Ancoli-Israel.

"By asking a few more questions in every intake, the neurologist is more likely to determine if there are any occult sleep disorders that need to be addressed. By improving sleep in general, one is more likely to also improve any REM abnormalities," she said.

Disease Indicator?

In an accompanying editorial, Michael S. Jaffee, MD, vice chair of neurology at the University of Florida in Gainesville, and colleagues note that the study raises the question of whether REM sleep "could serve as a biomarker for general health."

"Since the known roles of REM sleep do not easily suggest a causal link with mortality...it seems more likely that REM sleep reduction is either a crude marker of health or specific disease states that decrease REM sleep may play an important role in contributing to mortality," they write.

Neurologists should remember that certain medications affect sleep architecture, the editorialists advise. They note that serotonin reuptake inhibitors, selective serotonin and norepinephrine reuptake inhibitors, and tricyclic antidepressants reduce REM sleep, and that gabapentin, prazosin, and bupropion, on the other hand, increase REM sleep. However, data regarding whether these medications have an effect on mortality are insufficient.

The editorialists write that the study findings are a "welcome addition to the literature and demonstrate definitively that the association between sleep and mortality extends beyond the simple measure of total sleep time."

Funding for the MrOS and WSC studies was provided by the National Institutes of Health and the National Institute on Aging. Ancoli-Israel consults for Eisai and Merck on matters unrelated to the study. Redline has received grants and personal fees from Jazz Pharmaceuticals, consulting fees from Respicardia, and personal fees from Eisai unrelated to the study. Jaffee served on a data and safety monitoring board for Helius Medical Technologies and consulted for the National Collegiate Athletic Association and the Department of Defense.

JAMA Neurol. Published online July 6, 2020. Abstract, Editorial

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