In the present study, we evaluated pre-existing PSGs of healthy university students without clinical RBD and observed RWA for one or more epochs in 88.0% participants, with an RWA index of 2.8%. This suggests that RWA has a high occurrence rate even in healthy young adults without parasomnia, and provides useful information for determining the natural history of age-related changes in RWA. Various scoring methods and cutoff values have been proposed for quantifying RWA [12,13,14], however, methods for measuring, quantifying, and evaluating RWA have not yet been standardized. Moreover, limited data exist on RWA in young, healthy adults, and a reference range for normal values has not been established. When RWA was evaluated in SM, in the control group, phasic EMG activity ranged from 4.3 to 19.8% and “any” EMG activity ranged from 8.4 to 21.6% [12, 13, 16, 19]. Moreover, “any” EMG activity was found in 12.8–13.2% individuals in their 20 s, when considering the 95th percentile values [16, 18]. The cutoffs for phasic and “any” EMG activity in SM were 15.5–16.3% and 19.5–21.6%, respectively [12, 13, 16, 19]. Some studies have reported that RWA was incidentally identified on PSG in 5.6% cases and that the cutoff value exceeded in 12% cases with incidental RWA [20, 21]. In other previous studies, the frequency of RWA exceeding the diagnostic cutoff value for RBD without dream-enacting behaviors ranged from 14 to 32% [12, 16]. The RWA EMG activities in this study restricted to young adults was lower than the cutoff values for prodromal RBD reported in previous studies. These activity values were in line with the definitions of phasic or tonic RWA proposed by several groups, including the Sleep Innsbruck Barcelona group and the Mayo Clinic group [12, 19, 22]. The RWA index (2.8%) was intermediate relative to the indices for patients with excessive daytime sleepiness (0.6%) and patients with narcolepsy (type 1, 9.2%; type 2, 3.9%) in a previous study [15]. Their EMG activity values were within normative values in terms of mean duration and amplitude, and their RWA index was lower than the cutoff value. A recent longitudinal study showed that the cutoff for RWA to distinguish between prodromal RBD and control was 6.3% for “any” EMG activity in the mentalis muscle [23]. In this study, however, the RWA index was lower, at 2.8%. None of them exceeded the cutoff values of 16.3% and 9.6% for the phasic and tonic RWA indices, respectively [12]. In addition, the phasic RWA duration in SM was 1.4 s, which was similar to the mean duration of 0.50–1.09 s (95th percentile) in SM in previous studies [16, 19]. In this way, although the RWA index for participants in their 20 s was below the cutoff for RBD diagnosis in this study, longitudinal follow-up is needed to determine if their RWAs will become pathological in the future. On the other hand, it was noteworthy that at least one epoch of EMG activity during REM sleep could be identified for 88% of healthy university students without clinical RBD. However, it is unclear whether the results of this study apply to all races, and future large-scale studies involving young adults from various ethnicities are warranted. The mean age of the individuals in previous studies that showed cutoff values was in the 60 s [12, 13, 19, 22], which may be one of the reasons for the discrepancy with the RWA activity in this study, which was conducted with individuals in their 20s. However, as the results of this study are real natural history data from healthy young adults with a mean age of 22.7 years, these values will serve as one of the standards for future RWA studies.
There are two possible clinical implications of RWA. First, it is a prodromal RBD and a biomarker for early neurodegeneration, and it is also a biomarker for phenoconversion because older individuals with high RWA are more likely to develop α-synucleinopathy [14, 24]. Second, it can be an indicator for definitive and differential diagnosis. RWA can be used as an indicator for the diagnosis of pediatric and adult narcolepsy [15, 25] and to distinguish between controls, patients with RBD, and patients with narcolepsy [12, 26]. It has been noted that there may be a spectrum between iRWA and RBD, described as prodromal RBD [27], so young adults with RWA in this study may also require a follow-up study. However, participants in this study may have healthy RWA, and the current presence of RWA does not necessarily mean that they will develop iRBD later. The clinical significance and prognosis of RWA may vary with age and disease, and data on the natural history of RWA remain limited. Since even healthy individuals may have RWA, long-term follow-up may be necessary. Therefore, a large longitudinal study is needed to investigate cutoff values for RWA by age group to distinguish between healthy individuals and affected patients. Although iRBD shows a difference depending on sex [28], investigation of the relationship between the incidence of RBD and the significantly longer duration of phasic RWA in young adult males than in females will be a future challenge. Most previous studies compared age groups and did not mention or find significant sex differences [16, 18, 29]. In the present study, significant sex differences were found only for the duration of phasic RWA, and no significant sex differences were observed for the other measures. This suggests that the small number of male participants influenced the results. Thus, future large-scale studies including age, race, and sex differences are warranted.
Because this study used overnight PSG data obtained for other research purposes, we were unable to assess EMG activity in the anterior tibialis and bilateral superficial flexor digitorum (FDS) muscles, which would be useful for accurate assessment of RWA. However, regarding RWA quantification, the guidelines from the International RBD Study Group recommend the quantification of SM and FDS EMG activities. However, quantification of only mentalis EMG activity is also acceptable [30]. In addition, RBD diagnosis using EMG of SM has been reported to be appropriate next to “any” SM and phasic FDS activity [31], and “any” SM activity assessment has a diagnostic performance that it relatively equivalent to that of SM + FDS or FDS activity assessment [32]. Therefore, we believe that this study, which examined the reality of RWA in SM among young adults in their 20 s, will make a significant contribution to future RBD research. Although narcolepsy cannot be completely ruled out because multiple sleep latency tests were not performed for participants with a high RWA index, the interview ruled out narcolepsy type 1 with typical symptoms such as sleep attacks and cataplexy. Although no obvious clinical symptoms of RBD were observed in the participants in this study, long-term follow-up is necessary as it cannot guarantee that RBD will not develop in the future. Therefore, while a longitudinal study is needed to confirm the future course of symptoms in these individuals, the results undeniably suggest that even healthy individuals exhibit such values. Nocturnal variability could not be validated because the data were obtained over a single night. Consequently, we cannot rule out the possibility that it reflects an incidental physiology. In addition, we could not accurately assess the apnea-hypopnea index because there were no useful sleep-disordered breathing data to rule out increased EMG activity due to respiratory events. No imaging studies, such as brain magnetic resonance imaging, were performed. The sleep status of participants immediately before the study was based on verbal self-reports rather than on objective assessments such as sleep diaries or PSG; thus, the effects of sleep deprivation cannot be completely ruled out. Finally, since this is a single-center, retrospective study with a small sample size and limited to young adults, the generalizability of the present findings is limited. Larger longitudinal studies on RWA among healthy young adults that overcome the above limitations are warranted in the future.