Zinc Status Alters Alzheimer's Disease Progression through NLRP3-Dependent Inflammation.

Alzheimer's disease is a devastating neurodegenerative disease with a dramatically increasing prevalence and no disease-modifying treatment. Inflammatory lifestyle factors increase the risk of developing Alzheimer's disease. Zinc deficiency is the most prevalent malnutrition in the world and may be a risk factor for Alzheimer's disease potentially through enhanced inflammation, although evidence for this is limited. Here we provide epidemiological evidence suggesting that zinc supplementation was associated with reduced risk and slower cognitive decline, in people with Alzheimer's disease and mild cognitive impairment. Using the APP/PS1 mouse model of Alzheimer's disease fed a control (35 mg/kg zinc) or diet deficient in zinc (3 mg/kg zinc), we determined that zinc deficiency accelerated Alzheimer's-like memory deficits without modifying amyloid ß plaque burden in the brains of male mice. The NLRP3-inflammasome complex is one of the most important regulators of inflammation, and we show here that zinc deficiency in immune cells, including microglia, potentiated NLRP3 responses to inflammatory stimuli in vitro, including amyloid oligomers, while zinc supplementation inhibited NLRP3 activation. APP/PS1 mice deficient in NLRP3 were protected against the accelerated cognitive decline with zinc deficiency. Collectively, this research suggests that zinc status is linked to inflammatory reactivity and may be modified in people to reduce the risk and slow the progression of Alzheimer's disease.SIGNIFICANCE STATEMENT Alzheimer's disease is a common condition mostly affecting the elderly. Zinc deficiency is also a global problem, especially in the elderly and also in people with Alzheimer's disease. Zinc deficiency contributes to many clinical disorders, including immune dysfunction. Inflammation is known to contribute to the risk and progression of Alzheimer's disease; thus, we hypothesized that zinc status would affect Alzheimer's disease progression. Here we show that zinc supplementation reduced the prevalence and symptomatic decline in people with Alzheimer's disease. In an animal model of Alzheimer's disease, zinc deficiency worsened cognitive decline because of an enhancement in NLRP3-driven inflammation. Overall, our data suggest that zinc status affects Alzheimer's disease progression, and that zinc supplementation could slow the rate of cognitive decline.

Changes in Glial Support of the Hippocampus during the Development of an Alzheimer's Disease-like Pathology and Their Correction by Mitochondria-Targeted Antioxidant SkQ1.

Astrocytes and microglia are the first cells to react to neurodegeneration, e.g., in Alzheimer's disease (AD); however, the data on changes in glial support during the most common (sporadic) type of the disease are sparse. Using senescence-accelerated OXYS rats, which simulate key characteristics of sporadic AD, and Wistar rats (parental normal strain, control), we investigated hippocampal neurogenesis and glial changes during AD-like pathology. Using immunohistochemistry, we showed that the early stage of the pathology is accompanied by a lower intensity of neurogenesis and decreased astrocyte density in the dentate gyrus. The progressive stage is concurrent with reactive astrogliosis and microglia activation, as confirmed by increased cell densities and by the acquisition of cell-specific gene expression profiles, according to transcriptome sequencing data. Besides, here, we continued to analyze the anti-AD effects of prolonged supplementation with mitochondria-targeted antioxidant SkQ1. The antioxidant did not affect neurogenesis, partly normalized the gene expression profile of astrocytes and microglia, and shifted the resting/activated microglia ratio toward a decrease in the activated-cell density. In summary, both astrocytes and microglia are more vulnerable to AD-associated neurodegeneration in the CA3 area than in other hippocampal areas; SkQ1 had an anti-inflammatory effect and is a promising modality for AD prevention and treatment.

Effects of vitamin E supplementation on the risk and progression of AD: a systematic review and meta-analysis.

Objective: The association between vitamin E supplementation and Alzheimer's disease (AD) was controversial because of conflicting data in the literature. This study was designed to systematically evaluate evidence about the efficacy of vitamin E supplementation not only on the risk but also on the progression of AD. Design: Five electronic databases were searched for studies published up to June 2017. Articles reporting vitamin E supplementation and AD were included, and the random-effect model was performed for the meta-analysis about the relationship between vitamin E supplementation and AD. Results: Five cohort studies and three randomized controlled trial (RCT) studies (total n = 14,262) involving 1313 cases about vitamin E effects on the risk of AD and 244 cases about effects on progression of AD. The pooled RR for vitamin E supplemental and risk of AD was 0.81 [95% CI: 0.50-1.33, I 2 = 69.2%]. Suitable data could not be extracted to do meta-analysis as there was no unified standard of outcome measure for studies on AD progression. We carefully analyzed and evaluated the authenticity and accuracy of every single trial, while reliable evidence could not be obtained. Conclusions: From what we do, neither the synthetic data on risk of AD nor the critical review on progression of AD could provide enough evidence on our research. Thus, we cannot draw a specific conclusion on the association or correlation between Vitamin E and AD.

36-month LipiDiDiet multinutrient clinical trial in prodromal Alzheimer's disease.

INTRODUCTION: The LipiDiDiet trial investigates the effects of the specific multinutrient combination Fortasyn Connect on cognition and related measures in prodromal Alzheimer's disease (AD). Based on previous results we hypothesized that benefits increase with long-term intervention. METHODS: In this randomized, double-blind, placebo-controlled trial, 311 people with prodromal AD were recruited using the International Working Group-1 criteria and assigned to active product (125 mL once-a-day drink) or an isocaloric, same tasting, placebo control drink. Main outcome was change in cognition (Neuropsychological Test Battery [NTB] 5-item composite). Analyses were by modified intention-to-treat, excluding (ie, censoring) data collected after the start of open-label active product and/or AD medication. RESULTS: Of the 382 assessed for eligibility, 311 were randomized, of those 162 participants completed the 36-month study, including 81 with 36-month data eligible for efficacy analysis. Over 36 months, significant reductions in decline were observed for the NTB 5-item composite (-60%; between-group difference 0.212 [95% confidence interval: 0.044 to 0.380]; P = 0.014), Clinical Dementia Rating-Sum of Boxes (-45%; P = 0.014), memory (-76%; P = 0.008), and brain atrophy measures; small to medium Cohen's d effect size (0.25-0.31) similar to established clinically relevant AD treatment. DISCUSSION: This multinutrient intervention slowed decline on clinical and other measures related to cognition, function, brain atrophy, and disease progression. These results indicate that intervention benefits increased with long-term use.

Nutraceutical and Probiotic Approaches to Examine Molecular Interactions of the Amyloid Precursor Protein APP in Drosophila Models of Alzheimer's Disease.

Studies using animal models have shed light into the molecular and cellular basis for the neuropathology observed in patients with Alzheimer's disease (AD). In particular, the role of the amyloid precursor protein (APP) plays a crucial role in the formation of senile plaques and aging-dependent degeneration. Here, we focus our review on recent findings using the Drosophila AD model to expand our understanding of APP molecular function and interactions, including insights gained from the fly homolog APP-like (APPL). Finally, as there is still no cure for AD, we review some approaches that have shown promising results in ameliorating AD-associated phenotypes, with special attention on the use of nutraceuticals and their molecular effects, as well as interactions with the gut microbiome. Overall, the phenomena described here are of fundamental significance for understanding network development and degeneration. Given the highly conserved nature of fundamental signaling pathways, the insight gained from animal models such as Drosophila melanogaster will likely advance the understanding of the mammalian brain, and thus be relevant to human health.

Alzheimer's Disease and Type 2 Diabetes Mellitus: The Use of MCT Oil and a Ketogenic Diet.

Recently, type 2 diabetes mellitus (T2DM) has been reported to be strongly associated with Alzheimer's disease (AD). This is partly due to insulin resistance in the brain. Insulin signaling and the number of insulin receptors may decline in the brain of T2DM patients, resulting in impaired synaptic formation, neuronal plasticity, and mitochondrial metabolism. In AD patients, hypometabolism of glucose in the brain is observed before the onset of symptoms. Amyloid-ß accumulation, a main pathology of AD, also relates to impaired insulin action and glucose metabolism, although ketone metabolism is not affected. Therefore, the shift from glucose metabolism to ketone metabolism may be a reasonable pathway for neuronal protection. To promote ketone metabolism, medium-chain triglyceride (MCT) oil and a ketogenic diet could be introduced as an alternative source of energy in the brain of AD patients.

EVOO Polyphenols Relieve Synergistically Autophagy Dysregulation in a Cellular Model of Alzheimer's Disease.

(1) Background: Autophagy, the major cytoplasmic process of substrate turnover, declines with age, contributing to proteostasis decline, accumulation of harmful protein aggregates, damaged mitochondria and to ROS production. Accordingly, abnormalities in the autophagic flux may contribute to many different pathophysiological conditions associated with ageing, including neurodegeneration. Recent data have shown that extra-virgin olive oil (EVOO) polyphenols stimulate cell defenses against plaque-induced neurodegeneration, mainly, through autophagy induction. (2) Methods: We carried out a set of in vitro experiments on SH-SY5Y human neuroblastoma cells exposed to toxic Aß1-42 oligomers to investigate the molecular mechanisms involved in autophagy activation by two olive oil polyphenols, oleuropein aglycone (OleA), arising from the hydrolysis of oleuropein (Ole), the main polyphenol found in olive leaves and drupes and its main metabolite, hydroxytyrosol (HT). (3) Results: Our data show that the mixture of the two polyphenols activates synergistically the autophagic flux preventing cell damage by Aß1-42 oligomers., in terms of ROS production, and impairment of mitochondria. (4) Conclusion: Our results support the idea that EVOO polyphenols act synergistically in autophagy modulation against neurodegeneration. These data confirm and provide the rationale to consider these molecules, alone or in combination, as promising candidates to contrast ageing-associated neurodegeneration.

The role of nutrition in Alzheimer's disease.

The aging population is a significant social, medical and economic problem due to increasing prevalence of chronic diseases in elderly population. Alzheimer's disease (AD) is the most common form of dementia and the most common neurodegenerative disease. It is characterized by a progressive deterioration of memory and cognitive function. So far, there is neither an effective prevention nor cure for dementia, so more and more attention is paid to the prevention of this group of diseases, particularly to the appropriate diet. Preventive intervention gives the best results if introduced before the first symptoms of dementia, i.e., around the age of 50. This is when the nutritional status, number of synapses, cognition, and neuropathological changes in the nervous system compensate each other, which increases the chances of staying healthy for a longer period of time. It has been proven that dietary habits, which lead to the development of cardiovascular and metabolic diseases, significantly increase the risk of dementia. On the other hand, a Mediterranean diet rich in antioxidants, fiber and omega-3 polyunsaturated fatty acids may have a protective effect on the neurodegenerative process. The beneficial effect of many nutrients on the course of AD has been demonstrated. These include: glutathione, polyphenols, curcumin, coenzyme Q10, vitamins B6, B12, folic acid, unsaturated fatty acids, lecithin, UA, caffeine and some probiotic bacteria. A diet rich in saturated fatty acids and branched-chain amino acids (BCAA) promotes the progression of dementia. Dietary intervention should be introduced as early as possible to minimize the risk of developing dementia. The Mediterranean and DASH diets have been documented to protect against AD. However, the MIND diet is reported to be much more effective in preventing cognitive decline/dementia than either the Mediterranean or DASH diets alone.

Protective role of functional food in cognitive deficit in young and senile rats.

Cognitive decline and neurodegenerative diseases pose a significant burden on healthcare resources both in developed and developing countries which is a major socio-economic and healthcare concern. Alzheimer's disease is the most common form of progressive neurodegenerative dementia of the aged brain. Aluminum is a constituent of antacids, deodorants, kitchenware and food additives which allows easy access into the body posing risk to development of senile dementia of Alzheimer's type. Virgin coconut oil was declared as a potential cognitive strengthener. Assessment of cognitive and memory-enhancing effects of virgin coconut oil in senile and young rats to gain vital insights into its effective use in the prevention of neurodegeneration in dementia/Alzheimer's disease-like manifestations and alleviate cognitive dysfunction and learning impairment with neuronal damage imparted by daily oral intake of aluminum. Alzheimer's disease-like symptoms and memory impairment were experimentally induced using oral anhydrous aluminum chloride given daily for five successive weeks in young and old age albino rats. Treatment groups received virgin coconut oil to assess protection during the experimental period. Behavioral test, Morris water maze was conducted before/after induction/treatment. At the end of the experimental period, cholinergic, dopaminergic, noradrenergic and serotonergic neurotransmission as well as brain-derived neurotrophic factor were being investigated, in addition to immunochemical and histopathological examination of targeted brain regions. Virgin coconut oil significantly improved cholinergic activity and monoaminergic neurotransmission. Moreover, immunochemical and histopathological examination revealed marked protection with virgin coconut oil against aluminum-induced Alzheimer's disease-like pathology and cognitive deficit.

Protective Effects of Compounds from Cimicifuga dahurica against Amyloid Beta Production in Vitro and Scopolamine-Induced Memory Impairment in Vivo.

Cimicifuga dahurica has traditionally been used as an antipyretic, analgesic, and anti-inflammatory agent and as a treatment for uterine and anal prolapse. This study has investigated the potential beneficial effects of this medicinal plant and its components on Alzheimer's disease (AD) with a focus on amyloid beta (Aß) production and scopolamine-induced memory impairment in mice. An ethanol extract from C. dahurica roots decreased Aß production in APP-CHO cells [Chinese hamster ovarian (CHO) cells stably expressing amyloid precursor protein (APP)], as determined by an enzyme-linked immunosorbent assay and Western blot analysis. Then, the compounds isolated from C. dahurica were tested for their antiamyloidogenic activities. Four compounds (1-4) efficiently interrupted Aß generation by suppressing the level of ß-secretase in APP-CHO cells. Moreover, the in vivo experimental results demonstrated that compound 4 improved the cognitive performances of mice with scopolamine-induced disruption on behavioral tests and the expression of memory-related proteins. Taken together, these results suggest that C. dahurica and its constituents are potential agents for preventing or alleviating the symptoms of AD.

Souvenaid for Alzheimer's disease.

BACKGROUND: Souvenaid is a dietary supplement with a patented composition (Fortasyn Connect™)which is intended to be used by people with Alzheimer's disease (AD). It has been designed to support the formation and function of synapses in the brain, which are thought to be strongly correlated with cognitive function. If effective, it might improve symptoms of Alzheimer's disease and also prevent the progression from prodromal Alzheimer's disease to dementia. We sought in this review to examine the evidence for this proposition. OBJECTIVES: To assess the effects of Souvenaid on incidence of dementia, cognition, functional performance, and safety in people with Alzheimer's disease. SEARCH METHODS: We searched ALOIS, i.e. the specialised register of the Cochrane Dementia and Cognitive Improvement Group, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), Web of Science (ISI Web of Science), Cinahl (EBSCOhost), Lilacs (BIREME), and clinical trials registries up to 24 June 2020. We also reviewed citations of reference lists of landmark papers, reviews, and included studies for additional studies and assessed their suitability for inclusion in the review. SELECTION CRITERIA: We included randomised, placebo-controlled trials which evaluated Souvenaid in people diagnosed with mild cognitive impairment (MCI) due to AD (also termed prodromal AD) or with dementia due to AD, and with a treatment duration of at least 16 weeks. DATA COLLECTION AND ANALYSIS: Our primary outcome measures were incidence of dementia, global and specific cognitive function, functional performance, combined cognitive-functional outcomes and adverse events. We selected studies, extracted data, assessed the quality of trials and intended to conduct meta-analyses according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. We present all outcomes grouped by stage of AD. MAIN RESULTS: We included three randomised, placebo-controlled trials investigating Souvenaid in 1097 community-dwelling participants with Alzheimer's disease. One study each included participants with prodromal AD, mild AD dementia and mild-to-moderate AD dementia. We rated the risks of bias of all trials as low. One study (in prodromal AD) was funded by European grants. The other two studies were funded by the manufacturer of Souvenaid. One trial investigated the incidence of dementia in people with prodromal AD at baseline, and found little to no difference between the Souvenaid group and the placebo group after 24 months (RR 1.09, 95% CI 0.82 to 1.43; 1 trial, 311 participants; moderate quality of evidence). In prodromal AD, and in mild and mild-to-moderate Alzheimer's disease dementia, Souvenaid probably results in little or no difference in global or specific cognitive functions (moderate quality of evidence). Everyday function, or the ability to perform activities of daily living, were measured in mild and mild-to-moderate AD dementia. Neither study found evidence of a difference between the groups after 24 weeks of treatment (moderate quality of evidence). Two studies investigated combined cognitive-functional outcomes with the Clinical Dementia Rating Sum of Boxes and observed conflicting results. Souvenaid probably results in slight improvement, which is below estimates of meaningful change, in participants with prodromal Alzheimer's disease after 24 months (moderate quality of evidence), but probably has little to no effect in mild-to-moderate Alzheimer's disease dementia after 24 weeks (moderate quality of evidence). Adverse effects observed were low in all trials, and the available data were insufficient to determine any connection with Souvenaid. AUTHORS' CONCLUSIONS: Two years of treatment with Souvenaid probably does not reduce the risk of progression to dementia in people with prodromal AD. There is no convincing evidence that Souvenaid affects other outcomes important to people with AD in the prodromal stage or mild-to-moderate stages of dementia. Conflicting evidence on combined cognitive-functional outcomes in prodromal AD and mild AD dementia warrants further investigation. Adverse effects of Souvenaid seem to be uncommon, but the evidence synthesised in this review does not permit us to make a definitive statement on the long-term tolerability of Souvenaid. The effects of Souvenaid in more severe AD dementia or in people with AD at risk of nutritional deficiencies remain unclear.

Nutritional Lipidomics in Alzheimer's Disease.

Lipids constitute almost 60% of the brain's dry weight, and they are thought to be involved in inflammation, neurotransmission and synaptic plasticity. The brain mostly contains sphingolipids, glycerophospholipids and cholesterol which are abundant in myelin and neuronal membranes. The recent rise of the promising area of lipidomic data can be used as a diagnosing tool at the early stages of Alzheimer's disease allowing novel therapeutic targets. In this review, altered lipid metabolites as well as the impact of diet in the progress of Alzheimer's disease (AD) are analyzed.

Healthy Effects of Plant Polyphenols: Molecular Mechanisms.

The increasing extension in life expectancy of human beings in developed countries is accompanied by a progressively greater rate of degenerative diseases associated with lifestyle and aging, most of which are still waiting for effective, not merely symptomatic, therapies. Accordingly, at present, the recommendations aimed at reducing the prevalence of these conditions in the population are limited to a safer lifestyle including physical/mental exercise, a reduced caloric intake, and a proper diet in a convivial environment. The claimed health benefits of the Mediterranean and Asian diets have been confirmed in many clinical trials and epidemiological surveys. These diets are characterized by several features, including low meat consumption, the intake of oils instead of fats as lipid sources, moderate amounts of red wine, and significant amounts of fresh fruit and vegetables. In particular, the latter have attracted popular and scientific attention for their content, though in reduced amounts, of a number of molecules increasingly investigated for their healthy properties. Among the latter, plant polyphenols have raised remarkable interest in the scientific community; in fact, several clinical trials have confirmed that many health benefits of the Mediterranean/Asian diets can be traced back to the presence of significant amounts of these molecules, even though, in some cases, contradictory results have been reported, which highlights the need for further investigation. In light of the results of these trials, recent research has sought to provide information on the biochemical, molecular, epigenetic, and cell biology modifications by plant polyphenols in cell, organismal, animal, and human models of cancer, metabolic, and neurodegenerative pathologies, notably Alzheimer's and Parkinson disease. The findings reported in the last decade are starting to help to decipher the complex relations between plant polyphenols and cell homeostatic systems including metabolic and redox equilibrium, proteostasis, and the inflammatory response, establishing an increasingly solid molecular basis for the healthy effects of these molecules. Taken together, the data currently available, though still incomplete, are providing a rationale for the possible use of natural polyphenols, or their molecular scaffolds, as nutraceuticals to contrast aging and to combat many associated pathologies.

Palmitoylethanolamide: A Nutritional Approach to Keep Neuroinflammation within Physiological Boundaries-A Systematic Review.

Neuroinflammation is a physiological response aimed at maintaining the homodynamic balance and providing the body with the fundamental resource of adaptation to endogenous and exogenous stimuli. Although the response is initiated with protective purposes, the effect may be detrimental when not regulated. The physiological control of neuroinflammation is mainly achieved via regulatory mechanisms performed by particular cells of the immune system intimately associated with or within the nervous system and named "non-neuronal cells." In particular, mast cells (within the central nervous system and in the periphery) and microglia (at spinal and supraspinal level) are involved in this control, through a close functional relationship between them and neurons (either centrally, spinal, or peripherally located). Accordingly, neuroinflammation becomes a worsening factor in many disorders whenever the non-neuronal cell supervision is inadequate. It has been shown that the regulation of non-neuronal cells-and therefore the control of neuroinflammation-depends on the local "on demand" synthesis of the endogenous lipid amide Palmitoylethanolamide and related endocannabinoids. When the balance between synthesis and degradation of this bioactive lipid mediator is disrupted in favor of reduced synthesis and/or increased degradation, the behavior of non-neuronal cells may not be appropriately regulated and neuroinflammation exceeds the physiological boundaries. In these conditions, it has been demonstrated that the increase of endogenous Palmitoylethanolamide-either by decreasing its degradation or exogenous administration-is able to keep neuroinflammation within its physiological limits. In this review the large number of studies on the benefits derived from oral administration of micronized and highly bioavailable forms of Palmitoylethanolamide is discussed, with special reference to neuroinflammatory disorders.

Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases.

Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain's utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain's metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain's glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer's disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson's disease and cognitive benefits in patients with-or at risk of-Alzheimer's disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data.

The potential role of nutritional components in improving brain function among patients with Alzheimers disease: a meta-analysis of RCT studies.

OBJECTIVE: To find out the potential role of nutritional components in improving brain function among patients with Alzheimer`s disease (AD). METHODS: The correlation between nutrition and cerebral function in cases of AD has been the focus of 19 prospective randomised controlled trials (RCTs) with a combined research sample of 2297 patients. These RCTs are subject to systematic review and meta-analysis in the current paper RESULTS: Findings showed that chain-free secondary saturated fatty acids (SFA) and trans fatty acids (TFA) occurred in higher concentrations in AD patients` brains than in controls. Furthermore, neuroinflammation was caused by remodelling of the lipid membrane and AD patients` cognitive function was impacted by alterations in tyrosine, tryptophan, purine, and tocopherol pathway metabolomics. Moreover, in cases of mild-to-moderate AD, reduction in functionality was induced by administration of alpha-tocopherol for more than 12 months. Consumption of Souvenaid helps in synaptic synthesis, which enhances functional connectivity. Furthermore, consumption of the B vitamins folate, cobalamin and pyridoxine at dosages of 0.8 mg, 0.5 mg and 20 mg per day, respectively, over a period of one year resulted in lower plasma tHcy levels and brain atrophy. CONCLUSION: Chain-free SFA and TFA occur in greater amounts in the brains of individuals with AD than in those without AD.

Role of green tea catechins in prevention of age-related cognitive decline: Pharmacological targets and clinical perspective.

Over the past decade, a wide range of scientific investigations have been performed to reveal neuropathological aspects of cognitive disorders; however, only limited therapeutic approaches currently exist. The failures of conventional therapeutic options as well as the predicted dramatic rise in the prevalence of cognitive decline in the coming future show the necessity for novel therapeutic agents. Recently, a wide range of research has focused on pharmacological activities of green tea catechins worldwide. Current investigations have clarified mechanistic effects of the catechins in inflammatory cascades, oxidative damages, different cellular transcription as well as transduction pathway in various body systems. It has been demonstrated that green tea polyphenols prevent age-related neurodegeneration through improvement of endogenous antioxidant defense mechanisms, modulation of neural growth factors, attenuation of neuroinflammatory pathway, and regulation of apoptosis. The catechins exhibited beneficial effects in cellular and animal models of neurodegenerative diseases including Alzheimer's disease, MS, and Parkinson's disease. The present review discusses the current pharmacological targets, which can be involved in the treatment of cognitive decline and addresses the action of catechin derivatives elicited from green tea on the multiple neural targets.

Lessons learned from recent clinical trials of ketogenic diet therapies in adults.

PURPOSE OF REVIEW: Although ketogenic diet therapies (KDTs) were first developed as a treatment for patients with epilepsy, their potential efficacy for a broader number of neurologic and nonneurologic disorders and conditions has been explored over the last 10-20 years. The most recent clinical trials of KDTs in adults have highlighted common methodological aspects that can either facilitate or thwart appropriate risk/benefit analyses, comparisons across studies, and reproducibility of findings in future studies. RECENT FINDINGS: Recent evidence suggests that KDTs not only improve seizure control, but also improve other neurologic conditions, including nonmotor Parkinson's disease symptoms. Therapies targeting nutritional ketosis without comprehensive diet modification improve cognition and cerebral blood flow in Alzheimer's disease patients. KDTs lower hemoglobin A1c levels and diabetes medication use in patients with Type 2 diabetes and mixed results have been observed when used for performance enhancement in athletes and healthy volunteers. SUMMARY: Clinical studies of KDTs show promise for a variety of clinical indications. Future studies should factor in high potential participant attrition rates and utilize consistent and standard reporting of diet type(s), compliance measures, and side-effects to enable the reproducibility and generalizability of study outcomes.

Effects of nutrient and bioactive food components on Alzheimer's disease and epigenetic.

Alzheimer's disease (AD) is the most common form of dementia in the elderly and is a chronic neurodegenerative disease that is becoming widespread. For this reason, in recent years factors affecting the development, progression and cognitive function of the AD have been emphasized. Nutrients and other bioactive nutrients are among the factors that are effective in AD. In particular, vitamins A, C and E, vitamins B1, B6 and B12, folate, magnesium, choline, inositol, anthocyanins, isoflavones etc. nutrients and bioactive nutrients are known to be effective in the development of AD. Nutrients and nutrient components may also have an epigenetic effect on AD. At the same time, nutrients and bioactive food components slow down the progression of the disease. For this reason, the effect of nutrients and food components on AD was examined in this review.

Neuro-nutrients as anti-alzheimer's disease agents: A critical review.

Alzheimer's disease (AD) is characterized by a massive neuronal death causing memory loss, cognitive impairment and behavioral alteration that ultimately lead to dementia and death. AD is a multi-factorial pathology controlled by molecular events such as oxidative stress, protein aggregation, mitochondrial dysfunction and neuro inflammation. Nowadays, there is no efficient disease-modifying treatment for AD and epidemiological studies have suggested that diet and nutrition have a significant impact on the development of this disorder. Indeed, some nutrients can protect all kind of cells, including neurons. As prevention is better than cure, life style improvement, with a special emphasis on diet, should seriously be considered as an anti-AD track and intake of nutrients promoting neuronal health is the need of the hour. Diets rich in unsaturated fatty acids, polyphenols and vitamins have been shown to protect against AD, whereas saturated fatty acids-containing diets deprived of polyphenols promote the development of the disease. Thus, Mediterranean diets, mainly composed of fruits, vegetables and omega-3 fatty acids, stand as valuable, mild and preventive anti-AD agents. This review focuses on our current knowledge in the field and how one can fight this devastating neurodegenerative disorder through the simple proper modification of our life style.