Melatonin in elderly patients Rixt F. Riemersma-van der Lek, Dick F. Swab, Jos Twisk, Elly M. Hol, Witte J.G. Hoogendijk and Eus Van Someren* Sleep and Cognition Laboratory, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands (Received 10 March 2007; final version received 29 January 2008) Long-term combined light and melatonin treatment improve sleep, cognition and mood in demented elderly patients. A good night’s sleep sustains cognitive performance. Disturbed sleep, a frequent decisive factor in caregiver burden and institutionalisation of Alzheimer patients, may thus augment their characteristic impairments. We hypothesized that a possible reversible lack of activation of the circadian clock could contribute to sleep problems, and performed the first controlled human study on the effect of prolonged combined stimulation with light and melatonin. During a 3.5 year double-blind placebo-controlled randomized follow-up study, 189 elderly patients received daily supplementation of the circadian synchronisers light (+ lux, whole-day), and/or melatonin (2.5 mg). Half-yearly assessments were made of actigraphic sleep–wake rhythm estimates, cognition (MMSE), and non-cognitive symptoms. Combined light and melatonin treatment improved nocturnal restlessness by 8 + 3% per year (p 5 0.01), resulting in increased sleep duration and efficiency and a more pronounced 24-hour amplitude. Light improved cognition by 0.9 + 0.4 MMSE points or 5% (p 1⁄4 0.04). Light ameliorated depressive symptoms by 19% (Cornell Scale for Depression in Dementia). Melatonin ameliorated the worsening of psychiatric symptoms that occurred in subjects about to drop out of the study due to nursing home placement or death (Questionnaire format of the Neuropsychiatric Inventory). A negative effect of melatonin on affect (Philadelphia Geriatric Centre Affect Rating Scale) was counteracted in combination with bright light. Combined treatment also attenuated aggressive behaviour (Cohen-Mansfield Agitation Index). Both light and melatonin treatment enhanced the nocturnal rise of the 24-hour saliva melatonin rhythm, as measured in the absence of melatonin gifts. Melatonin treatment however also resulted in an increased daytime melatonin level, which was associated with an attenuation of diurnal activity. This first study on long-term stimulation of the human circadian timing system showed that improvement of the sleep–wake rhythm contributed to attenuation of cognitive The complete description of this study is available in: Riemersma-van der Lek et al. 2008. JAMA 299:2642–2655. *Corresponding author. Email: e.van.someren@nin.knaw.nl Biological Rhythm Research Vol. 40, No. 1, February 2009, 83–84 ISSN 0929-1016 print/ISSN 1744-4179 online! 2009 Taylor & Francis DOI: 10.1080/09291010802067155 http://www.informaworld.com D ow nl oa de d by [V rij e U ni ve rs ite it A m ste rd am ] a t 0 3: 36 2 0 A pr il 20 15 decline, with an affect exceeding that achieved with acetylcholinesterase inhibitors. Light improved non-cognitive symptoms, whereas melatonin may aggravate withdrawal behaviour and should – for long-term treatment in demented elderly – preferably be given in a lower dosage and in combination with bright light. 84 R.F. Riemersma-van der Lek et al. D ow nl oa de d by [V rij e U ni ve rs ite it A m ste rd am ] a t 0 3: 36 2 0 A pr il 20 15