Less REM Sleep Associated With Higher Mortality Risk in Older Adults

Eileen B. Leary, PhD, RPSGT, clinical scientist, Jazz Pharmaceuticals

Eileen B. Leary, PhD, RPSGT

An analysis of a cross-sectional study of more than 4000 patients from the Outcomes of Sleep Disorders in Older Men Sleep Study (MrOS; n = 2675) and Wisconsin Sleep Cohort (WSC; n = 1386) suggests that lower amounts of rapid eye movement (REM) sleep is associated with an increased risk of all-cause mortality in middle-aged and older adults.¹

Ultimately, over the 12.1-year period of the MrOS study, which began in 2003, there was a 13% higher mortality rate for every 5% reduction in REM sleep, which was confirmed with the second cohort in the 20.8 years of the WSC study, which began in 1988. The study was conducted by a group of researchers including Eileen B. Leary, PhD, RPSGT, clinical scientist, Jazz Pharmaceuticals.

“A robust association was found between percentage of REM sleep and mortality in 2 independent cohorts, which persisted across different causes of death and multiple sensitivity analyses. Given the complex underlying biologic functions, further studies are required to understand whether the relationship is causal,” Leary et. al wrote. They noted that accelerated brain aging may be a better marker than risk factor for mortality as it could be a cause of less REM sleep, though studies will need to confirm this.

“Strategies to preserve REM sleep may influence clinical therapies and reduce mortality risk, particularly for adults with less than 15% REM,” Leary and colleagues concluded.

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In an accompanying editorial, Michael S. Jaffee, MD; Liza H. Ashbrook, MD; and Milena K. Pavlova, MD, wrote that while these data do not imply a causal relationship, the neurologist community should be aware of them, as it brings into question the possibility that REM sleep could serve as a general health biomarker.²

“Fundamentally, our understanding of the function of REM sleep is still incomplete. In recent years, the role of REM sleep in memory consolidation and synaptic remodeling and pruning has become [clearer],” Jaffee et al. wrote. They clarified since the understood roles of REM sleep do not clearly suggest there is 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.”

The MrOS cohort was 100% men, with a mean age of 76.3 years (standard deviation [SD], 5.5), of which 91.5% (n = 2448) were white. They were followed for a median of 12.1 years (interquartile range [IQR], 7.8—13.2). The WSC cohort was 54.3% men (n = 753), with a mean age of 51.5 years (SD, 8.5), of which 94.6% (n = 1311) were white. They were followed for a median of 20.8 years (IQR, 17.9–22.4).

In MrOS, the percentage of REM sleep varied from 0% to 43.9% and was normally distributed. The total mean percentage of REM sleep was 19.2% (SD, 6.6%) with a mean time in REM sleep of 69.7 minutes (SD, 28.6). From the lowest quartile to the highest, those values increased from 14.8% to 23.6% (quartile 1: <14.8% REM, n = 677; quartile 2: 14.8%—19.4% REM, n = 662; quartile 3: 19.5%–23.5% REM, n = 667; quartile 4: >23.6% REM, n = 669).

There were 1404 deaths (52.5%) over the follow-up period in MrOS, with a 13% higher all-cause mortality rate for every 5% reduction in REM sleep (hazard ratio [HR], 1.13; 95% CI, 1.08—1.19) after adjusting for covariates. Cardiovascular disease-related mortality continued this association (HR, 1.11; 95% CI, 1.02–1.20), as did other mortality (HR, 1.19; 95% CI, 1.11–1.28). Cancer-related mortality was not significantly altered by lower REM (HR, 1.06; 95% CI, 0.96–1.17). Those with <15% REM sleep had a higher mortality rate compared with those with ≥15% for all mortality definitions (HR range, 1.20–1.35).

For the WSC cohort, the mean number of minutes in REM sleep was 67.8 (SD, 28.9) and a percentage of REM sleep range of 0% to 43.0%, similar to the MrOS cohort. Although the overall mean percentage of REM sleep was lower (mean, 17.6% [SD, 6.5%]). From the lowest to highest quartiles, the values increased from 13.3% to 21.8% (quartile 1: <13.3% REM, n = 345; quartile 2: 13.3%—17.5% REM, n = 348; quartile 3: 17.6%–21.7% REM, n = 347; quartile 4: >21.8% REM, n = 346).

In part due to the younger age of the WSC group, there were fewer deaths (184 [13.3%]). For a 5% reduction in REM sleep, the effect size on the risk of all-cause mortality was also significant (HR, 1.17; 95% CI, 1.03—1.34). This was also the case for and non-cardiovascular disease and non-cancer-related mortality (HR, 1.26; 95% CI, 1.01–1.58), despite the inclusion of both men and women, longer follow-up period, reduced samples size, and event frequency. For cardiovascular disease-related mortality and cancer-related mortality, the findings were also similar, though with wider confidence intervals (cardiovascular: HR, 1.13 [95% CI, 0.87–1.45]; cancer: HR, 1.13 [95% CI, 0.91–1.40]). Those with <15% REM sleep had a higher mortality rate compared with individuals with ≥15% (OR range, 1.36 to 1.78) for all mortality definitions saver for cardiovascular (HR, 1.00; 95% CI, 0.52–1.90).

“Sensitivity analyses showed findings persisted in subgroups with sleep duration between 5—8 and 6–8 hours (except cancer), without depression, severe sleep apnea, and in those not using medications that may affect REM,” Leary and colleagues noted. “In sum, decreased REM sleep was an indicator of mortality risk across a broad age range, which is consistent with the study evaluating REM sleep and mortality in the Sleep Heart Health Study. When stratified by sex, there was a higher rate of all-cause mortality in women compared with men.”

REFERENCES

1. Leary Eb, Watson KT, Ancoli-Israel S, et al. Association of Rapid Eye Movement Sleep With Mortality in Middle-aged and Older Adults. JAMA Neurol. Published online July 6, 2020. doi:10.1001/jamaneurol.2020.2108.

2. Jaffee MS, Ashbrook LH, Pavlova MK. Should Neurologists Be Concerned With REM Sleep Quantity? JAMA Neurol. Published online July 6, 2020. doi:10.1001/jamaneurol.2020.2122.