Article

The role of nutrients in the prevention and treatment of Alzheimer's disease: Methodology for a systematic review

Department of Medical Anthropology, University of Oxford, Oxford, UK.
European Journal of Neurology (Impact Factor: 4.06). 09/2009; 16 Suppl 1(s1):8-11. DOI: 10.1111/j.1468-1331.2009.02736.x
Source: PubMed

ABSTRACT

There is a large body of existing data on nutrition in Alzheimer's disease (AD). We are conducting a systematic review of published scientific literature to determine the role of specific nutrients, both individually and in combination, in the prevention and treatment of AD. This will contribute towards a structured evidence base to help inform the clinical management of AD. The objective of the systematic review is to evaluate the strength of evidence from both observational cohort studies and randomized controlled trials on the role of fats, vitamins, antioxidants and other nutrients in the prevention and treatment of AD. We present here the methodology of our systematic review.

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    • "Many recent reviews on AD present compelling evidence for a decisive participation of severe oxidative stress in the development of neuropathology seen in this disease [1, 5, 6, 10, 19, 57, 65, 71, 73, 74]. Therefore, numerous compounds with antioxidant properties have been suggested for treatment of AD and other neurodegenerative diseases [24, 42, 61, 62, 78, 81]. "
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    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.
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    ABSTRACT: The increasing worldwide prevalence of dementia is a major public health concern. Findings from some epidemiological studies suggest that diet and nutrition may be important modifiable risk factors for development of dementia. In order to evaluate the strength of the available evidence of an association of dietary factors with dementia including Alzheimer's disease (AD), we systematically searched relevant publication databases and hand-searched bibliographies up to end July 2007. We included prospective cohort studies which evaluated the association of nutrient levels with the risk of developing dementia and randomized intervention studies examining the treatment effect of nutrient supplementation on cognitive function. One hundred and sixty studies, comprising ninety one prospective cohort studies and sixty nine intervention studies, met the pre-specified inclusion criteria. Of these, thirty-three studies (19 cohort and 14 randomized controlled trials) investigated the effects of folate, B-vitamins, and levels of homocysteine (a biomarker modifiable through B-vitamin supplementation) or fish/fatty acids and are the focus of the present report. Some observational cohort studies indicated that higher dietary intake or elevated serum levels of folate and fish/fatty acids and low serum levels of homocysteine were associated with a reduced risk of incident AD and dementia, while other studies reported no association. The results of intervention studies examining the effects of folic acid or fatty acid supplementation on cognitive function are inconsistent. In summary, the available evidence is insufficient to draw definitive conclusions on the association of B vitamins and fatty acids with cognitive decline or dementia, and further long-term trials are required.
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    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.
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