Elderly persons tend to go to bed earlier, and the duration of their sleep is often decreased. This has been interpreted as secondary to a lesser secretion of melatonin, as found in many studies,53 or to the fact that cell death in the SCN leads the remaining neurons to generate a shorter endogenous circadian rhythm with age. Indeed, experiments with partial destruction of the SCN in laboratory rodents have shown that the circadian

period find more becomes shorter under these conditions, but there are also negative findings. In elderly persons, the secretion of melatonin is decreased, Inhibitors,research,lifescience,medical and this decrease could in part be due to the lack of exposure to daytime light, since a trial in a small population of subjects indicated that exposure to light could increase the nocturnal secretion of melatonin with a concomitant improvement Inhibitors,research,lifescience,medical in sleep.54 There are, however, studies reporting no changes in melatonin with age in humans.55 The neurodegeneration of the nucleus basalis of Meynert, a major Inhibitors,research,lifescience,medical source of cholinergic innervation, might explain sleep alteration in dementia,

since this group of cells is involved in rest/activity and is among the structures that send efferent messages to the SCN.56 Measurements in human chronobiology Chronobiological protocols can be cumbersome for two reasons. First, because of the necessity to study several biological cycles. Indeed, one cannot conclude that a change occurred in the frequency of any phenomenon when the study duration is too short for repetitions of the phenomenon to have occurred. This is a challenging issue for

psychiatry, where many disorders show recurrent decompensations. An observation Inhibitors,research,lifescience,medical lasting 1 to 2 times the theoretical duration of a cycle is necessary to infer that one has indeed identified a periodic change and to measure the Inhibitors,research,lifescience,medical duration of that cyclic change. A clinical observation of a patient during a time equivalent to 3 to 4 times the theoretical duration of a cycle is necessary to conclude that a treatment has influenced the course of a recurrent disorder. When the manifestation recur below in shorter cycles, such as with 48-h rapid cycling bipolar disorder, or with the premenstrual syndromes, the duration of studies becomes a lesser constraint. The second reason for which chronobiological protocols are complex is the nature of the measured phenomena. Indeed, biological rhythms are found in brain waves, in hormone concentration in blood, and in cognitive abilities. Measuring these phenomena can be difficult and necessitate more or less invasive methods, while less invasive techniques only allow long-term studies. Among these, the simplest one remains the repeated use of questionnaires to evaluate subjective biological functions such as mood, energy, or pain.