Demographic characteristics associated with circadian rest-activity rhythm patterns: a cross-sectional study

Circadian rhythms describe the endogenous ~ 24-h oscillations of molecular, physiological and behavioral processes which evolved to synchronize biological functions to the environmental light-dark cycle [1]. Circadian rhythms have been observed in almost all life forms and play a critical role in human health. Disruption of circadian rhythms has been associated with poor health, including increased risk of neurodegenerative diseases [2, 3], metabolic syndrome, diabetes [4, 5], cardiovascular disease [6], and cancer [7].

Rest-activity rhythm (RAR), namely magnitude, timing and regularity of rest-activity patterns, is the most evident manifestation of the circadian rhythm and can be objectively quantified from accelerometry data. In a recent prospective study, accelerometry-derived metrics of RAR including amplitude (strength or magnitude of the rhythm), acrophase (timing of peak activity) and pseudo-F statistic (robustness of the rhythm) independently predicted increased risk of incident diabetes among older men [8]. Another longitudinal analysis of 2930 older men also reported that, compared with participants in the highest quartile of amplitude, mesor (mean activity level) and pseudo-F statistic, those who were in the lowest quartiles had nearly three times greater risk of developing Parkinson disease [9]. Risk of dementia or mild cognitive impairment have also been associated with decreased amplitude or delayed acrophase [10, 11]. Metrics of RAR irregularity such as decreased interdaily stability (IS, day-to-day stability of RAR) and increased intradaily variability (IV, fragmentation of RAR) have been linked with increased risk of cardiometabolic disorders [12], neurodegenerative diseases [3, 13], and mortality [14 –16], thus underscoring the critical role of RAR for human health.

Nonetheless, little is known about RAR patterns among general adults and its configuration by sex, age and race/ethnicity. Most of the population-level evidence from accelerometry is limited to standard physical activity levels [17 –19]. A small study [20] with 590 adults (80.6% women) assessed RAR patterns and did not observe changes of RAR amplitude with aging, contrary to established knowledge on age-related trajectories in endogenous circadian rhythms [21], possibly because of the small sample size and uneven sex distribution. Therefore, there is need for studies describing RAR composition in the general populations in real-life settings, given that intrinsic circadian rhythms as assessed by core body temperature or melatonin release varied with demographic characteristics in laboratory settings [21 –23].

To address the aforementioned gaps, the present study aimed to describe RAR patterns among general adults and to explore variations by sex, age and race/ethnicity using accelerometry data from a large sample from the US National Health and Nutrition Examination Survey (NHANES) 2011–2012 and 2013–2014.

This cross-sectional study was conducted and reported following recommendation of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement [24].

In this large, nationally representative US sample we found that women had higher RAR amplitude and mesor and also had a more stable and less fragmented rest-activity circadian rhythm than men. We also observed lower RAR amplitude and mesor, and more advanced RAR acrophase along with more stable and less fragmented RAR in older adults than in younger adults. RAR also varied among race/ethnicity, with the highest amplitude and mesor levels, and most stable (highest IS) and least fragmented (lowest IV) RAR observed in Hispanics, while the lowest amplitude and most unstable RAR was observed in non-Hispanic blacks. To our knowledge, this is the first study to systematically describe demographic factors associated with RAR patterns in a real-life setting using a large and, importantly, representative sample of US adults.

In line with findings from the UK Biobank and the FinHealth 2017 Survey [18, 19], accelerometry data showed slightly higher amplitude and mesor in women relative to men, indicating higher physical activity as estimated from the fitted curve. However, other reported men having higher or similar accelerometer-measured total physical activity levels compared with women [35, 36], with men being more likely to be sedentary and engaged in moderate-to-vigorous activities and women in light activities. Such discrepancy may be owed to the approach used to determine activity. Because amplitude and mesor are circadian rhythm-adjusted estimates of physical activity based on the fitted curve derived from the extended cosinor model, they may not align with conventionally measured physical activity levels, and especially may not reflect short bursts of vigorous activity. A prior small study showed that women had more stable RAR but showed similar fragmentation levels compared with men, possibly due to the small proportion of male participants (19.4%) and the small sample size (n = 590) [20]. Supporting this hypothesis and in line with our results, men were found to have a more fragmented RAR in a study with more balanced sex distribution [13]. The more stable RAR pattern in women could potentially result from the more frequent involvement of regular household activities [37]. When we explored interactions between sex and age, we found that the age-related RAR phase advance was attenuated in women compared to men. This aligns with data from a Spanish population study on chronotypes, showing that, in participants aged > 40 years, women are more evening-oriented [38]. Although underlying mechanisms are unclear, this observation may reflect potential effects of estrogens on the intrinsic circadian rhythm. The slightly shorter circadian period exhibited by women in comparison to men, which results in earlier intrinsic circadian phase [23, 39, 40], has been attributed to their higher level of estrogens. As estrogen levels decrease with aging, their shortening effects on the circadian period may be blunted, therefore leading to less striking phase advance in women than men. Sociocultural factors could also contribute to the observed sex differences in acrophase changes with aging. For instance, prior to retirement years, women may engage in housework and/or childcare activities before going to work in the early morning hours [38].

The association between aging and changes in circadian rhythm has been well established. Briefly, the phase of endogenous circadian rhythms advances and the amplitude dampens with aging [21]. Our findings that mesor and amplitude of RAR decreased while phase advanced in older adults are consistent with these data. Moreover, environmental factors such as reduced work-related physical activity [41] and diminished social interaction [42] may also contribute to decreased amplitude and mesor in older adults. On the other hand, we also unexpectedly found that older adults had more stable and less fragmented RAR than younger adults. This result is seemingly at variance with evidence of decreases in stability and increases in fragmentation relating to age-related neurodegenerative disorders, such as Parkinson's disease [43] and Alzheimer's disease [11, 13]. However, the association between circadian rhythms and neurodegenerative disease has been reported to be bidirectional, with neurodegenerative disease also affecting circadian rhythms [1, 3]. Moreover, the present study aimed to assess the association of RAR with age in the general population, which may account for the discrepancy. Accordingly, many studies showed decreased variability in activity in older adults [20, 43 –45]. It is plausible that the higher interdaily stability and lower intradaily variability of RAR in older adults may reflect their more rigid day-to-day routine.

Little is known about differences in RAR patterns associated with race/ethnicity [20, 46, 47]. Similar to our findings, a previous study with 590 adults showed that African-Americans and Asians had less stable and weaker accelerometry-derived rest-activity patterns compared to Whites [20]. Mechanisms of the observed racial/ethnic RAR disparities may be complex, resulting from both endogenous and exogenous factors. Genetic differences or biological factors could be potential cause for the observed racial/ethnic variations in our findings [22, 48], and other unmeasured environmental and/or socioeconomic factors, such as work stability, could also be contributors to the observed racial/ethnic pattern of RAR. Although prior laboratory studies [46, 47, 49] reported that, compared with white individuals, African-Americans had slightly shorter intrinsic circadian period (about 13 to 16 min shorter), which often lead to phase advancing [50], we did not find significant differences in acrophases between non-Hispanic blacks versus non-Hispanic whites. Similarly, a recent study also reported no significant difference between whites and blacks on circadian rhythms phase measured by dim light melatonin onset in free-living environment [51]. Potential explanation could be that entrainment of environmental factors may offset the minor circadian rhythms phase difference between the white and black populations. A significantly more delayed phase of RAR in non-Hispanic Asians compared with non-Hispanic whites was observed. Additionally, we noted that the increase in IS and decrease of IV seeing with aging was accentuated in NH-Asians compared to other racial/ethnic groups. Environmental determinants, such as immigration and lifestyle changes, may play a role in this findings, as we found that in this sample the proportion of Asians who lived in US 10 years or longer also increased with age (Additional file 1 Fig. S3). Studies have reported that Asians or Asian immigrants are usually sedentary during their leisure time and longer duration of residence in US has been linked to more leisure time physical activity [52, 53], potentially reflecting the process of settling down into new environment and culture. However, potential mechanisms remain speculative and further studies on racial/ethnic circadian rhythms disparities are needed.

Our findings provide important and novel insights into characteristics of RAR and their potential role on health and disease. First, we report that RAR at least partially reflected the age and sex variation of endogenous circadian rhythms. Supporting our findings, significant correlations between fragmentation of RAR and decreased amplitude of melatonin secretion [54] and between RAR acrophase and cortisol acrophase [55] have been observed. Hence, RAR metrics derived from accelerometry data may serve as complementary marker for assessing endogenous circadian rhythms patterning in epidemiological studies and our data provided a compelling hypothesis-generating foundation for future studies of endogenous circadian variations and their health implications among different populations. Second, the different patterns of RAR we observed based on sex and race/ethnicity may have implications for understanding and potentially addressing disparities in risk of diseases and premature death [56]. Likewise, the higher activity levels and most stable RAR exhibited by Hispanics may at least partially account for the well-known 'Hispanic paradox', according to which US Hispanic populations live longer than Whites despite their socioeconomic disadvantages [57, 58]. Our observations that non-Hispanic blacks had the lowest RAR amplitude and interdaily stability are also consistent with the greater risk of premature mortality [57, 59] suffered by African-Americans compared with other ethnic/racial groups. Last, as disruption of RAR has been associated with increased risk of neurodegenerative diseases [3, 13], cardiometabolic diseases [12] and cancer [7], findings from the present study support targeting RAR in preventive and therapeutic strategies to enhance public health.