J Pineal Res zyxwvutsrqponm 1998; 25:177-183 Printed zyxwvutsrqponm in the United States of Americ-I1 rights reserved. Copyright 0 zyx Munksgaord, 1998 zy Journal of Pineal Research ISSN 0742-3098 zy Melatonin effects on sleep, mood, and cognition in elderly with mild cognitive impairment Jean-Louis G, von Gizycki H, Zizi F. Melatonin effects on sleep, mood, and cognition in elderly with mild cognitive impairment. J. Pineal Res. 1998; 25: 177-183.0 Munksgaard, Copenhagen Abstract: The effects of immediate-releasemelatonin on circadian rest- activity profiles, cognition, and mood were investigated in ten elderly individuals with self-reported sleep-wake disturbances. Melatonin (6 mg), administered 2 hr before habitual bedtime, enhanced the rest-activity rhythm and improved sleep quality as observed in a reduction in sleep onset latency and in the number of transitions from sleep to wakefulness. However, total sleep time was not significantly increased nor was wake within sleep significantly reduced. The ability to remember previously learned items improved along with a significant reduction in depressed moods. No side effects or contraindications were reported by any of our participants during the 10 day trials. These data suggest that melatonin can safely improve some aspects of sleep, memory, and mood in the elderly in short-term use. Introduction Sleep-wake patterns, rest-activity cycles, body tem- perature, and hormonal secretions all display rhythms of approximately 24 hr [Moore-Ede et al., 19831. Malfunctions of the circadian timekeeping mechanism may result in an inability of the organ- ism to adapt to different environmental conditions. When the circadian generator, the suprachiasmatic nucleus (SCN), is ablated, a consequential loss of rhythmicity in several circadian functions is ob- served [Stephen and Zucker, 1972; Rusak and Zucker, 19791. A disorganization of circadian rhythms is noted in the elderly, indicated by a dampened amplitude of the rest-activity cycle, body temperature, and hormonal rhythms [Bliwise, 1993; van Someren et al., 19931. Circadian alterations have also been as- sociated with changes in cognitive functioning [Prinz et al., 1982; Flicker et al., 19931. A deficit in the amplitude of melatonin might underlie the disturbance of the sleep-wake cycle observed in the elderly, especially those who have dementia [Vitiello and Prinz, 1989; Witting et al., 1990; van Coeverden et al., 19911. Possibly, the melatonin deficit is related to a selective deterioration of SCN Girardin Jean-Louis,',' Hans von Gizycki,' and Ferdinand Zizi' zy 'Department of Psychiatry, University of California, San Diego; *The Psychophysiology Laboratory, College of Staten Island Key words: elderly - melatonin - actigraphy - circadian rhythm - rest-activity - cognition - mood Address reprint requests to Dr. Girardin Jean-Louis, Sleep and Circadian Rhythm Studies, University of California, San Diego, 4130 La Jolla Village Drive, Suite 206, La Jolla, CA 92037. E-mail: gjeanlouis@ucsd.edu Received February 3, 1998; accepted April 11, 1998. cell groups [i.e., arginine-vasopressin cells] [Swaab et al., 1985, 19961. Another circadian disturbance in the elderly is a phase-advance in hormonal secretions and reduced amplitude (e.g., melatonin, prolactin, thyroid stimu- lating hormone, and cortisol) [van Coevorden et al., 19911. Also, an increased intradaily variability and decreased interdaily stability of the circadian rhythm of activity has been described [McGinty and Stern, 1988; van Someren et al., 19961. Several preliminary reports have suggested that melatonin can be used to treat advanced and delayed sleep phase syndromes [Zaidan et al., 1994; Deacon et al., 1995; Lewy et al., 19951 and sleep-wake mal- adaptation caused by shift work [Arendt et al., 19951. Improvement has been observed in individuals with seasonal affective disorders [Lewy et al., 19871, sleep-wake disturbances induced by jet lag [Boulos and Rusak, 1982; Arendt et al., 19951, and insomnia [Garfinkel et al., 1995; Haimov et al., 19951. Press accounts suggest that an increasing num- ber of elderly individuals are currently ingesting me- latonin to improve their sleep without careful monitoring to ascertain its safety and efficacy. Al- though reports have described improved sleep in 177