Mediterranean diet and cognitive decline

AbstractObjective:To investigate the possible role of diet in age-related cognitive decline (ARCD) and cognitive impairment of both degenerative (Alzheimer's disease, AD) and vascular (vascular dementia, VaD) origin.Design:Literature review.Results:In an elderly population of southern Italy with a typical Mediterranean diet, high energy intake of monounsaturated fatty acids (MUFA) appeared to be associated with a high level of protection against ARCD. In addition, dietary fat and energy in the elderly seem to be risk factors, while fish consumption and cereals are found to reduce the prevalence of AD in European and North American countries. Finally, the relative risk of dementia (AD and VaD) was lower in the subjects of a French cohort who drank three or four glasses of red wine each day compared with total abstainers.Conclusion:Essential components of the Mediterranean diet – MUFA, cereals and wine – seem to be protective against cognitive decline. As such, dietary antioxidants and supplements, specific macronutrients of the Mediterranean diet, oestrogens and anti-inflammatory drugs may act synergistically with other protective factors, opening up new therapeutic interventions for cognitive decline

The AFHSC-Division of GEIS Operations Predictive Surveillance Program: a multidisciplinary approach for the early detection and response to disease outbreaks

The Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System Operations (AFHSC-GEIS) initiated a coordinated, multidisciplinary program to link data sets and information derived from eco-climatic remote sensing activities, ecologic niche modeling, arthropod vector, animal disease-host/reservoir, and human disease surveillance for febrile illnesses, into a predictive surveillance program that generates advisories and alerts on emerging infectious disease outbreaks. The program’s ultimate goal is pro-active public health practice through pre-event preparedness, prevention and control, and response decision-making and prioritization. This multidisciplinary program is rooted in over 10 years experience in predictive surveillance for Rift Valley fever outbreaks in Eastern Africa. The AFHSC-GEIS Rift Valley fever project is based on the identification and use of disease-emergence critical detection points as reliable signals for increased outbreak risk. The AFHSC-GEIS predictive surveillance program has formalized the Rift Valley fever project into a structured template for extending predictive surveillance capability to other Department of Defense (DoD)-priority vector- and water-borne, and zoonotic diseases and geographic areas. These include leishmaniasis, malaria, and Crimea-Congo and other viral hemorrhagic fevers in Central Asia and Africa, dengue fever in Asia and the Americas, Japanese encephalitis (JE) and chikungunya fever in Asia, and rickettsial and other tick-borne infections in the U.S., Africa and Asia

Molecular Determinants of Human Longevity

Aging can be considered the product of an interaction between genetic, environmental, and lifestyle factors, which in turn influence longevity that varies between and within species. Given the high complexity of the phenomenon, several theories have been proposed providing an insight in the role of genetic and environmental factors in the process of aging. The "disposable soma theory", the most attractive theory, as well as other evolutionary theories state that aging is not only under genetic control and can also be considered a result of the failure of homeostasis. Therefore, although most studies agree that genetics influence longevity in humans, the magnitude of this effect is debated. A study on children of nonagenarians indicated a strong relationship between genetic influences and longevity, as did a study that compared the life span of adopted children with those of their adoptive and biological parents. Nonetheless, studies on twins reared together and twins reared apart indicated a small genetic influence on longevity. In fact, in one study, genetic factors explained no more than 30% of the variance in longevity, and in another study, this variance was even less. However, these studies did not analyze the oldest survivors, nor did they compare the longer-living with the shorter-living subjects. In fact, a strong relationship between genetics and longevity was demonstrated when centenarians were included, suggesting that genetic control of longevity is greatest in the oldest adults. A recent study demonstrated that the siblings of centenarians are three to four times more likely to survive to the 10th decade of life, compared with siblings of noncentenarians. Furthermore, immediate ancestors of Jeanne Calment from France, who died at the age of 123 years, were shown to be 10 times more likely to reach age 80 years than the ancestral cohort. These studies support the concept that longevity is a familial trait likely to be inherited and points to extreme age as the phenotype for an initial approach in identifying chromosomal regions that harbor longevity-assurance genes. Therefore, although the debate of the importance on genetics in determining the reaching of extreme longevity is open, it is mandatory to study the role of genetic determinants of longevity in humans, and several studies have been focused on healthy centenarians. In fact, these exceptionally long-living individuals represent a model-not discussed-of successful aging, having escaped the major age-associated diseases, and with most of them maintaining good cognitive and functional status. When age is plotted against the log of mortality rate, it gives a straight line as the mortality rate increases exponentially with age. However, the log of mortality rate falls below the expected at the ages of 95-100 years, indicating that mortality rate is no longer increasing exponentially in this age group. Although the mortality rate from cancers increases by approximately 10% per decade, it actually decreases after the age of 90 years. Thus, those individuals who have achieved an age of 90 years or older seem to be biologically unique; they have escaped disease-related mortality and get the biological make-up for successful aging. Interestingly, because the ratio of women to men at age 100 is 5 to 1, the female phenotype contributes to longevity independent of other genetic characteristics. Thus, based on biological distinctions, differences in mortality pattern, and the marked decrease in cancer, centenarians are likely to possess the strongest genetic determinants of longevity. The identification of gene variants involved in aging and longevity presents an interesting challenge. The discovery of genetic variations that explain even 5%-10% of the variation in survival to extreme old age could yield important clues about the cellular and biochemical mechanisms that affect the aging process and susceptibility to age-associated diseases. Candidate gene approaches, in which a gene is chosen based on function and the presumption that alteration in its function may affect the phenotype, have met with some success. Nonetheless, the definition of longevity and its associated intermediate phenotypes is still being debated. Furthermore, in the absence of detailed genealogies and prospective data, it is not possible to know definitively which individuals are or will be long-lived, and which are or will not be long-lived. Finally, individuals who died at early ages in accidents or war, or even from diseases resulting from environmental or other genetic factors, may still have harbored longevity-assurance genes. Recently, Richard Miller proposed a classification of longevity genes in different categories; the first one includes genes that cause or accelerate aging, even though it is a point of debate whether or not genetic mutations exist in nature that actually either cause or accelerate aging (e.g., P53 gene, telomerase gene). The second category concerns genes that increase the risk of a specific illness early in life but do not appear to be related to aging (e.g., CF gene and cystic fibrosis), or alternatively, genes that increase the risk of specific illness that resembles some of the consequences of aging. The third category consists of genes that influence or cause age-related diseases (e.g., Alzheimer disease [AD] and apolipoprotein E [APOE] ε{lunate}4 allele). Because variations in these genes are also associated with increased mortality risk, it is likely that centenarians do not have many of these predisposing variations. However, because the frequency of disease alleles is reduced in centenarians versus younger controls selected from the population, the statistical power of an association study between centenarians and subjects with a specific disease should be increased. This should be particularly true when searching for alleles that have a relatively high frequency in the general population. The fourth class includes low-fitness genes that extend maximum life span, probably by slowing down aging, as observed in lower organism mutations. One approach to determining the significance of such genes in humans is to screen for polymorphisms of their human homologs and to determine the allele frequencies among specific human phenotypes such as centenarians and to compare them to ethnically matched younger controls or controls predisposed to premature mortality. The fifth and sixth categories concern, respectively, polymorphic genetic loci that influence the rate of aging, and genes that influence differences in life span among species (e.g., longevity-enabling genes). A useful approach to finding these life span genes may be association studies using centenarian sibships. Families highly clustered for longevity, with five or more centenarian siblings and multiple centenarian cousins, provide the potential opportunity to perform linkage studies, linking the extreme longevity phenotype to a specific gene or genes. The aim of this chapter is to examine in depth the current knowledge of the role of different genetic determinants in modulating aging and in reaching of extreme longevity in humans, with particular interest in centenarian studies. We reviewed studies belonging to the third Miller's class of longevity genes, concerning those genes that influence or cause age-related diseases. First, we focused our attention on genes involved in vascular risk and vascular-related diseases and discussed the evidence that genetic factors, likely to be linked to both vascular disease and AD, may have an additional role in determining human longevity. Second, we reviewed principal findings on genetic factors linked to inflammation (interleukin 6 [IL-6] gene and other cytokine genes) and regulating immune response

Polyunsaturated Fatty Acid and S-Adenosylmethionine Supplementation in Predementia Syndromes and Alzheimer's Disease: A Review

A growing body of evidence indicates that nutritional supplements can improve cognition; however, which supplements are effective remains controversial. In this review article, we focus on dietary supplementation suggested for predementia syndromes and Alzheimers disease (AD), with particular emphasis on S-adenosylmethionine (SAM) and polyunsaturated fatty acids (PUFA). Very recent findings confirmed that SAM can exert a direct effect on glutathione S-transferase (GST) activity. AD is accompanied by reduced GST activity, diminished SAM, and increased S-adenosylhomocysteine (SAH), the downstream metabolic product resulting from SAM-mediated transmethylation reactions, when deprived of folate. Therefore, these findings underscored the critical role of SAM in maintenance of neuronal health, suggesting a possible role of SAM as a neuroprotective dietary supplement for AD patients. In fact, very recent studies on early-stage AD patients and moderate- to late-stage AD patients were conducted with a nutriceutical supplementation that included SAM, with promising results. Given recent findings from randomized clinical trials (RCTs) in which n-3 PUFA supplementation was effective only in very mild AD subgroups or mild cognitive impairment (MCI), we suggest future intervention trials using measures of dietary supplementation (dietary n-3 PUFA and SAM plus B vitamin supplementation) to determine if such supplements will reduce the risk for cognitive decline in very mild AD and MCI. Therefore, key supplements are not necessarily working in isolation and the most profound impact, or in some cases the only impact, is noted very early in the course of AD, suggesting that nutriceutical supplements may bolster pharmacological approaches well past the window where supplements can work on their own. Recommendations regarding future research on the effects of SAM or n-3 PUFA supplementation on predementia syndromes and very mild AD include properly designed RCTs that are sufficiently powered and with an adequate length (e.g., 3–5 years of follow-up)