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Age-related sleep disruption and reduction in the circadian rhythm of urine output: contribution of nocturia
Duffy JF, Scheuermaier K, Loughlin KR
Current Aging Science 2016; 9: 34-43.
Commented by Prof. Donald L. Bliwise:
This is a unique study describing a protocol that, perhaps better than has ever been demonstrated previously, describes age differences in the circadian rhythm of urine production. While nocturia has long been known to be associated with deficiencies in AVP release resulting in urine production at night in the elderly, it has always been somewhat ambiguous as to whether this effect might represent a secondary effect of sleep interruption, versus a true disruption of the endogenous biological clock (i.e., a dysfunction of the circadian timing system). It is challenging to tease apart the effects of sleep disruption from impairment of circadian rhythms, however, one way that this can be done is a research protocol called the “Constant Routine.” In this highly rigorous, experimental protocol, patients are brought into the hospital for a stay of several days. During this protocol, they are confined to bed, kept continuously in constant dim light for 40 hours and are not allowed to sleep during this entire period. This is ensured by the continuous presence of technical staff during that entire 40 hour period, assigned on a 1:1 ratio. Moreover, fluid intake is aliquoted on an hourly basis and patients are fed a calorie-controlled snack every hour. Thus, factors known to affect urine production, such as fluid intake, activity level, posture and, of course, sleep itself, are rigidly controlled. Results from this protocol are presented in Figure 1 of the article and clearly show a dampening of the circadian rhythm of urine output with age. That is to say, older subjects show less urine production during daytime hours but also increased urine volume during nighttime hours. As described by researchers in chronobiology, this is termed a decreased “amplitude” of the rhythm.
Such age-dependent changes in urine output represent one component of many aspects of circadian physiology that change with aging. For example, the circadian rhythms of hormones such as prolactin, testosterone, melatonin, and thyroid stimulating hormone show dampening of their amplitude as well. The sleep/wake cycle itself is also subject to such changes. The latter is manifested both by fragmentation of sleep at night, as well as the tendency for drowsiness during the daytime, often leading to napping and age-dependent increases in drowsiness. In other words, the ability of the aged brain to consolidate state (either as continuous sleep or wakefulness) is altered with advancing age. In its most extreme form, such as occurs in some dementia patients, there may be no rhythm in sleep and wakefulness at all, and both states appear to occur haphazardly throughout the 24-hour day. It remains to be seen how urine production around 24 hours would also be impacted by such neurodegenerative changes.
Aging is associated with a marked increase in sleep complaints, and one factor causing sleep disruption is waking to void (nocturia). Urological surveys have found that few young adults report nocturia symptoms, but about half of those in their 60's and nearly 80% of older age groups are affected. Sleep surveys have found nocturia is a major cause of sleep disruption, with a majority of older adults with sleep disruption citing the need to void as the cause of their awakening. While much of the urological literature implies that nocturia causes sleep disruption, age-related changes in sleep depth and continuity may make it more likely that an older adult will wake in response to a filling bladder, or that an older adult will wake for another reason and then decide to void. There is also evidence that age-related changes in the amplitude of circadian rhythms contribute to nocturia. There is a well-described circadian rhythm in urine output, and evidence of circadian rhythmicity in some diuretic and anti-diuretic hormones. In this article, we describe how age-related changes in sleep depth and continuity and age-related changes in circadian rhythm amplitude may contribute to nocturia, and how nocturia in turn leads to sleep disruption. Better understanding of how changes in sleep and circadian rhythmicity impact nocturia may lead to improved treatments and better quality of life for older adults.