Original Contribution Fragmentation and Stability of Circadian Activity Rhythms Predict Mortality The Rotterdam Study Downloaded from

Circadian rhythms and sleep patterns change as people age. Little is known about the associations between circadian rhythms and mortality rates. We investigated whether 24-hour activity rhythms and sleep characteristics independently predicted mortality. Actigraphy was used to determine the stability and fragmentation of the 24-hour activity rhythm in 1,734 persons (aged 45-98 years) from the Rotterdam Study (2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013). Sleep was assessed objectively using actigraphy and subjectively using sleep diaries to estimate sleep duration, sleep onset latency, and waking after sleep onset. The mean follow-up time was 7.3 years; 154 participants (8.9%) died. Sleep measures were not related to mortality after adjustment for health parameters. In contrast, a more stable 24-hour activity rhythm was associated with a lower mortality risk (per 1 standard deviation, hazard ratio = 0.83, 95% confidence interval: 0.71, 0.96), and a more fragmented rhythm was associated with a higher mortality risk ( per 1 standard deviation, hazard ratio = 1.22, 95% confidence interval: 1.04, 1.44). Low stability and high fragmentation of the 24-hour activity rhythm predicted all-cause mortality, whereas estimates from actigraphy and sleep diaries did not. Disturbed circadian activity rhythms reflect age-related alterations in the biological clock and could be an indicator of disease. circadian activity rhythm; elderly; mortality; sleep Abbreviations: ADL, activities of daily living; CI, confidence interval; HR, hazard ratio; PSQI, Pittsburgh Sleep Quality Index; SD, standard deviation. Most physiological processes, including body temperature, hormone secretion, and sleep-wake timing, are regulated in cycles that last approximately 24 hours, called circadian rhythms. Circadian rhythms and sleep patterns change as people age (1). Elderly people sleep less during the night, have more fragmented sleep, have more difficulty in falling asleep, tend to fall asleep and wake up earlier, take more naps, and report a lower sleep quality (2-6). The longitudinal associations of these changes with adverse health consequences and mortality are not well understood. In previous studies, investigators found that people who slept for short durations each night (≤6 hours) and had poor sleep quality had higher risks of diabetes and cardiovascular diseases Few studies have investigated the associations of circadian rhythms with mortality. In the elderly, the amplitude of several physiological circadian rhythms is reduced compared with that of younger people, as is the stability of the day-night rhyth