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The use of chronobiotics in the resynchronization of the sleep/wake cycle. Therapeutical application in the early phases of Alzheimer's disease.

Recent patents on endocrine, metabolic & immune drug discovery
May 1, 2011
Daniel P Cardinali et al. (3 authors)
Journal ArticleResearch Support, Non-U.S. Gov'tReviewHuman Study
Study Details

Study Goal

The researchers aimed to evaluate melatonin's effectiveness in improving sleep quality and cognitive performance in individuals with mild cognitive impairment (MCI) and its potential as a therapeutic tool in early Alzheimer's disease.

Results Summary

The study found that daily evening melatonin improved sleep quality and cognitive performance in MCI patients, with consistent results across five double-blind, randomized placebo-controlled trials and one open-label retrospective study.

Population

Individuals with mild cognitive impairment (MCI) and early Alzheimer's disease.

Effective Dosage

Not specified

Duration

Not specified

Interactions

None mentioned

Extracted Claims (5)
InterventionDirectionEndpointPopulationDosageImpactClaim #
melatonin
increase
sleep-wake cycle
blind people and in individuals suffering from circadian rhythm sleep disorders, like delayed sleep phase syndrome, jet lag or shift-work
-
synchronizes
#1
melatonin
decrease
daily melatonin production
Alzheimer's disease (AD) patients
-
decreases with age, and in several pathologies, attaining its lowest values
#2
melatonin replacement
increase
sundowning and other sleep wake disorders
fully developed AD
-
effective to treat
#3
daily evening melatonin
increase
sleep quality and cognitive performance
MCI
-
improves
#4
melatonin
neutral
-
early phases of AD
-
can be a useful ad-on therapeutic tool
#5
Abstract

Treatment of circadian rhythm disorders, whether precipitated by intrinsic factors (e.g., sleep disorders, blindness, mental disorders, aging) or by extrinsic factors (e.g., shift work, jet-lag) has led to the development of a new type of agents called "chronobiotics". The term "chronobiotic" defines a substance displaying the therapeutic activity of shifting the phase or increasing the amplitude of the circadian rhythms. The prototype of this therapeutic group is melatonin, whose administration synchronizes the sleep-wake cycle in blind people and in individuals suffering from circadian rhythm sleep disorders, like delayed sleep phase syndrome, jet lag or shift-work. Daily melatonin production decreases with age, and in several pathologies, attaining its lowest values in Alzheimer's disease (AD) patients. About half of dementia patients have severe disruptions in their sleep-wakefulness cycle. Melatonin replacement is effective to treat sundowning and other sleep wake disorders in fully developed AD, although controversial data on this point exist. Indeed, large interindividual differences between patients suffering from AD exist and can explain these erratic results. Theoretically the effect of melatonin could be more consistent at an earlier stage of the disease, i.e., mild cognitive impairment (MCI), an etiologically heterogeneous syndrome that precedes dementia. PubMed was searched using Entrez for articles including clinical trials. Search terms were "Alzheimer" "mild cognitive impairment" and "melatonin". Full publications were obtained and references were checked for additional material where appropriate. Only clinical studies with empirical treatment data were reviewed. Five double blind, randomized placebo-controlled trials and 1 open-label retrospective study (N = 651) all agree in indicating that treatment with daily evening melatonin improves sleep quality and cognitive performance in MCI. The analysis of published evidence and patents indicates that melatonin can be a useful ad-on therapeutic tool in the early phases of AD.

Medical Subject Headings (MeSH)
Alzheimer DiseaseCircadian RhythmCognitive DysfunctionFemaleHumansMaleMelatoninSleep Disorders, Circadian RhythmSuprachiasmatic NucleusWakefulness
Study Links
Quality Scores
SafetyNot Assessed
Efficacy85/10
Quality90/10
Citation Metrics
Total Citations17
Citations/Year1.2
Relative Citation Ratio0.58
NIH Percentile31.2%
Research Impact Scores
APT Score0.25
Weight Score1.42
Normalized Score0.72
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