Clinical aspects of melatonin intervention in Alzheimer's disease progression

Abstract

Melatonin secretion decreases in Alzheimer´s disease (AD) and this decrease has been postulated as responsible for the circadian disorganization, decrease in sleep efficiency and impaired cognitive function seen in those patients. Half of severely ill AD patients develop chronobiological day-night rhythm disturbances like an agitated behavior during the evening hours (so-called "sundowning"). Melatonin replacement has been shown effective to treat sundowning and other sleep wake disorders in AD patients. The antioxidant, mitochondrial and antiamyloidogenic effects of melatonin indicate its potentiality to interfere with the onset of the disease. This is of particularly importance in mild cognitive impairment (MCI), an etiologically heterogeneous syndrome that precedes dementia. The aim of this manuscript was to assess published evidence of the efficacy of melatonin to treat AD and MCI patients. PubMed was searched using Entrez for articles including clinical trials and published up to 15 January 2010. Search terms were "Alzheimer" and "melatonin". Full publications were obtained and references were checked for additional material where appropriate. Only clinical studies with empirical treatment data were reviewed. The analysis of published evidence made it possible to postulate melatonin as a useful ad-on therapeutic tool in MCI. In the case of AD, larger randomized controlled trials are necessary to yield evidence of effectiveness (i.e. clinical and subjective relevance) before melatonin´s use can be advocated.

Keywords: Alzheimer's disease; Melatonin; clinical trials.; minimal cognitive impairment; neuropsychological tests.

Fig. (1)

Retrospective analysis of 60 outpatients complaining of MCI symptoms, 35 of which received daily 3 to 9 mg of a fast-release melatonin preparation p.o. at bedtime for 9 to 24 months. Melatonin was given in addition to the individual standard medication prescribed by the attending psychiatrist. The other 25 subjects selected received the medication prescribed by the attending psychiatrist which did not include melatonin. Δ Variation of neuropsychological evaluation including are depicted. See text for further details. Shown are the means ± SEM. P values denote differences in Z values between final and initial neuropsychological evaluation after a non parametric Mann-Whitney U test.

Fig. (2)

Retrospective analysis of 60 outpatients complaining of MCI symptoms, 35 of which received daily 3 to 9 mg of a fast-release melatonin preparation p.o. at bedtime for 9 to 24 months. For details see Legend to Fig. (1). Shown are the means ± SEM.