Clinical Aspects of Melatonin Intervention in Alzheimer’s Disease Progression

Departamento de Docencia e Investigación, Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina, Buenos Aires, Argentina.
DNA research: an international journal for rapid publication of reports on genes and genomes (Impact Factor: 3.05). 09/2010; 8(3):218-27. DOI: 10.2174/157015910792246209
Source: PubMed


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.

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    • "Several beneficial effects of melatonin have been observed in numerous models of neurodegenerative disorders, including Alzheimer's disease (AD), although a halting of disease progression is not or only poorly demonstrable in humans (Srinivasan et al., 2006; Cardinali et al., 2010). A potentially important aspect of the relationship between melatonin and aging, especially inflammaging, concerns the changes of melatonin secretion that are frequently observed in the course of senescence. "
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    • "Furthermore, an exacerbation of these changes in the circadian system is also found with Alzheimer's disease (AD) [6]. Mild cognitive impairment (MCI) is a heterogeneous condition in which subjects belonging to the amnestic subgroup present a high risk of developing dementia [7], with conversion rates to AD close to 12% per year [8]. Compared to the relatively large number of articles devoted to the study of circadian alterations in AD, only scarce and sometimes contradictory data are available on the possible impairment of the circadian system in MCI. "
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    ABSTRACT: . Patients with dementia, especially Alzheimer’s disease, present several circadian impairments related to an accelerated perturbation of their biological clock that is caused by the illness itself and not merely age-related. Thus, the objective of this work was to elucidate whether these circadian system alterations were already present in patients with mild cognitive impairment (MCI), as compared to healthy age-matched subjects. Methods . 40 subjects (21 patients diagnosed with MCI, 74.1 ± 1.5 y.o., and 19 healthy subjects, 71.7 ± 1.4 y.o.) were subjected to ambulatory monitoring, recording wrist skin temperature, motor activity, body position, and the integrated variable TAP (including temperature, activity, and position) for one week. Nonparametrical analyses were then applied. Results . MCI patients exhibited a significant phase advance with respect to the healthy group for the following phase markers: temperature M5 (mean ± SEM: 04:20 ± 00:21 versus 02:52 ± 00:21) and L10 (14:35 ± 00:27 versus 13:24 ± 00:16) and TAP L5 (04:18 ± 00:14 versus 02:55 ± 00:30) and M10 (14:30 ± 00:18 versus 13:28 ± 00:23). Conclusions . These results suggest that significant advances in the biological clock begin to occur in MCI patients, evidenced by an accelerated aging of the circadian clock, as compared to a healthy population of the same age.
    BioMed Research International 07/2014; DOI:10.1155/2014/524971 · 2.71 Impact Factor
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    • "Similarly, administration of melatonin in the late night or early morning may delay melatonin onset [48] although the soporific effects of melatonin administered during the daytime need to be considered. While prior studies in MCI have certainly shown improvements in sleep with melatonin administration (see [12] for a review), melatonin is generally given at or before bedtime, and effects on circadian phase were not established. Ultimately, the significance of such interventions would be assessed not only by their effects on sleep and circadian timing, but also by their capacity to enhance broader aspects of functioning including cognition. "
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    ABSTRACT: Background: While it is evident that Alzheimer's disease is associated with disturbed sleep and circadian rhythms, the extent to which such changes are evident in older people 'at risk' of developing dementia is unknown. Objective: In this study, we aimed to determine whether patients with mild cognitive impairment (MCI) demonstrated significant alterations in the timing of melatonin secretion onset and amount, as well as sleep architecture. Methods: Thirty patients with MCI and 28 age-matched controls underwent psychiatric, medical, and neuropsychological assessment, followed by overnight polysomnography and dim light melatonin onset assessment. Participants also performed an episodic memory task while in the laboratory. Dim light melatonin onset was computed using a standardized algorithm, and area under the curve was computed for melatonin secretion. Sleep architecture measures including wake after sleep onset and latency to rapid eye movement sleep were derived. Results: Patients with MCI had advanced timing of their melatonin secretion onset relative to controls, but the levels of melatonin secreted did not differ between groups. The MCI group also had greater wake after sleep onset and increased rapid eye movement sleep latency. There were differential associations between dim light melatonin onset and cognition between the two groups, with earlier dim light melatonin onset being associated with poorer memory performance in MCI patients. Conclusion: Circadian misalignment and sleep disruption is evident in patients with MCI, and is consistent with changes observed in Alzheimer's disease. Such findings could be a marker for disease trajectory, and may even be implicated in disease pathogenesis.
    Journal of Alzheimer's disease: JAD 10/2013; 38(4). DOI:10.3233/JAD-131217 · 4.15 Impact Factor
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