By Alan Z. Segal, MD
Associate Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Segal reports no financial relationships relevant to this field of study.
SYNOPSIS: Total sleep duration declines with increasing age, as does the fraction of sleep spent in rapid eye movement (REM) sleep. The decline in REM is associated with increasing mortality, but it is not clear if this is a cause or a marker of declining health and declining brain function.
SOURCE: 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 2020;77:1241.
Although the precise physiological benefit of sleep remains poorly understood, lack of sleep has multiple consequences, including cardiovascular disease, depression, impairments in cognition, and overall mortality. Much of sleep research uses subjects’ self-reporting of sleep duration and quality, but cannot address details such as sleep stages, e.g., differentiating between rapid eye movement (REM) and non-REM (NREM) sleep. Although wearable technologies (such as Fitbit, Whoop, or Apple Watch) increasingly are capable of using accelerometry and pulse oximetry monitoring to accurately identify sleep stages, polysomnography remains the gold standard in quantification of REM and NREM (stages 1, 2, or 3) sleep. The two large, prospective cohorts studied here gathered valuable comprehensive polysomnography data and can be considered among the “Framingham Studies” of sleep research. Now approximately 20 years old, the Outcomes of Sleep Disorders in Older Men (MrOS) and the Wisconsin Sleep Cohort (WSC) both are showing a rising degree of mortality over time and, therefore, increasingly are capable of providing insight into this crucial outcome measure.
There are important differences between MrOS and WSC. MrOS enrolled 2,675 subjects, all men, and generally older (mean age of 76 years at enrollment between 2003 and 2005). Overall, 52% of the MrOS cohort has died. In contrast, WSC, with a total of 1,386 subjects, enrolled men and women roughly equally and had a mean age of 51 years at enrollment in 1998. Both studies showed a relationship between REM sleep and longevity. MrOS showed a 13% increase in mortality for every 5% reduction in REM sleep. Men achieving < 15% REM sleep showed a mortality hazard ratio (HR) of 1.35 compared to those who spent > 15% of their sleep in REM. WSC had a longer period of follow up (on average, 20 years compared to 12 years in MrOS), but overall mortality was only 13%, given that it studied younger patients. WSC showed a 1.17 HR of death among those with < 15% of the night in REM sleep. Additionally, both studies showed that the mortality benefit was specifically the result of REM duration rather than overall sleep quantity. Results were comparable whether subjects slept for shorter (five- to seven-hour) compared to longer (six- to eight-hour) periods. REM duration ranged from 0% to 44% (19% on average) in MrOS and 0% to 43% (18% on average) in WSC. All of these data were statistically significant, controlling for covariables, such as race/ethnicity, educational level, body mass index, hypertension, smoking status, alcohol, caffeine, and use of sleep aids.
The results reported here were similarly shown in the Sleep Heart Health Study (SHHS), a large cohort study of 6,600 subjects with obstructive sleep apnea (OSA).1 However, in SHHS, the benefit of REM sleep was found only in women, likely because of the overwhelmingly deleterious effect of OSA among male subjects. Other studies of REM vs. NREM sleep have cast doubt on the specificity of REM as a marker of effective sleep. Although some have shown benefits of REM for cognitive performance and mood, others suggest that total sleep time, or quantity of slow wave (stage 3) sleep rather than REM, seemed more favorable in the prevention of obesity and the metabolic syndrome. As the authors observed, the results reported here are generalizable, given that they were replicated in two well-validated cohorts, diverse in gender and age. They also pointed out obvious weaknesses, including that both studies were more than 90% of white ethnicity. The authors also acknowledged one of the thorniest issues in this type of sleep research — that is, reverse causality. It remains unknown whether REM sleep is merely a marker of brain and overall physical health, rather than a direct cause of longevity.
- Butler MP, Emch JT, Rueschman M, et al. Apnea-hypopnea event duration predicts mortality in men and women in the Sleep Heart Health Study. Am J Respir Crit Care Med 2019;99:903-912.