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The Association between Mushroom Consumption and Mild Cognitive Impairment: A Community-Based Cross-Sectional Study in Singapore

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Abstract

We examined the cross-sectional association between mushroom intake and mild cognitive impairment (MCI) using data from 663 participants aged 60 and above from the Diet and Healthy Aging (DaHA) study in Singapore. Compared with participants who consumed mushrooms less than once per week, participants who consumed mushrooms >2 portions per week had reduced odds of having MCI (odds ratio = 0.43, 95% CI 0.23-0.78, p = 0.006) and this association was independent of age, gender, education, cigarette smoking, alcohol consumption, hypertension, diabetes, heart disease, stroke, physical activities, and social activities. Our cross-sectional data support the potential role of mushrooms and their bioactive compounds in delaying neurodegeneration.

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... Interestingly, two studies have reported that the supplementation of L. edodes derived β-glucan for consecutive 28 days can improve gut microbiome dysbiosis in aged mice [18], and thereby improve insulin resistance in insulin-deficient type 2 diabetic rats [19]. Moreover, a recent cross-sectional study has shown that mushroom consumption had reduced the incidence rate of mild cognitive impairment in aged individuals in Singapore [20]. These findings suggest that the main ingredient of L. edodes, β-glucan, may have the potential to regulate gut microbiota and gut-brain axis. ...
... Collectively, these data demonstrated that L. edodes β-glucan ameliorated the cognitive deficits induced by chronic HF diet, and these neuroprotective effects potentially occurred through the improvement of the colon-microbiota-brain axis. Previously, edible mushrooms have shown beneficial effects on cognition in a cross-sectional study [20]. Here we reported that the main ingredient of edible mushroom, L. edodes β-glucan, improved the gut microbiota-brain axis. ...
... Here we reported that the main ingredient of edible mushroom, L. edodes β-glucan, improved the gut microbiota-brain axis. Therefore, the beneficial effects of β-glucan may contribute to the ability of mushroom in the improvement of cognitive function, as described previously in the human study [20]. ...
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Background Long-term high fat (HF) diet intake can cause neuroinflammation and cognitive decline through the gut-brain axis. (1, 3)/(1, 6)-β-glucan, an edible polysaccharide isolated from medical mushroom, Lentinula edodes ( L. edodes ), has the potential to remodel gut microbiota. However, the effects of L. edodes derived β-glucan against HF diet-induced neuroinflammation and cognitive decline remain unknown. This study aimed to evaluate the neuroprotective effect and mechanism of dietary L edodes β-glucan supplementation against the obesity-associated cognitive decline in mice fed by a HF diet. Methods C57BL/6J male mice were fed with either a lab chow (LC), HF or HF with L. edode s β-glucan supplementation diets for 7 days (short-term) or 15 weeks (long-term). Cognitive behavior was examined; blood, cecum content, colon and brain were collected to evaluate metabolic parameters, endotoxin, gut microbiota, colon, and brain pathology. Results We reported that short-term and long-term L. edodes β-glucan supplementation prevented the gut microbial composition shift induced by the HF diet. Long-term L. edodes β-glucan supplementation prevented the HF diet-induced recognition memory impairment assessed by behavioral tests (the temporal order memory, novel object recognition and Y-maze tests). In the prefrontal cortex and hippocampus, the β-glucan supplementation ameliorated the alteration of synaptic ultrastructure, neuroinflammation and brain-derived neurotrophic factor (BDNF) deficits induced by HF diet. Furthermore, the β-glucan supplementation increased the mucosal thickness, upregulated the expression of tight junction protein occludin, decreased the plasma LPS level, and inhibited the proinflammatory macrophage accumulation in the colon of mice fed by HF diet. Conclusions This study revealed that L. edodes β-glucan prevents cognitive impairments induced by the HF diet, which may occur via colon-brain axis improvement. The finding suggested that dietary L. edodes β-glucan supplementation may be an effective nutritional strategy to prevent obesity-associated cognitive decline.
... Interestingly, two studies have reported that the supplementation of L. edodes derived β-glucan for consecutive 28 days can improve gut microbiome dysbiosis in aged mice [18], and thereby improve insulin resistance in insulin-de cient type 2 diabetic rats [19]. Moreover, a recent cross-sectional study has shown that mushroom consumption had reduced the incidence rate of mild cognitive impairment in aged individuals in Singapore [20]. These ndings suggest that the main ingredient of L. edodes, β-glucan, may have the potential to regulate gut microbiota and gut-brain axis. ...
... Collectively, these data demonstrated that L. Edodes β-glucan ameliorated the cognitive de cits induced by chronic HF diet, and these neuroprotective effects potentially occurred through the improvement of the colon-microbiota-brain axis. Previously, edible mushrooms have shown the bene cial effects on cognition in a cross-sectional study [20]. Here we reported that the main ingredient of edible mushroom, L. Edodes β-glucan, improved the gut microbiotabrain axis. ...
... Here we reported that the main ingredient of edible mushroom, L. Edodes β-glucan, improved the gut microbiotabrain axis. Therefore, the bene cial effects of β-glucan may contribute to the ability of mushroom in the improvement of cognitive function, as described previously in the human study [20]. ...
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Background: Long-term high fat (HF) diet intake can cause neuroinflammation and cognitive decline through the gut-brain axis. (1, 3)/(1, 6)-β-glucan, an edible polysaccharide isolated from medical mushroom, Lentinula edodes (L. edodes), has the potential to remodel gut microbiota. However, the effects of L. edode derived β-glucan against HF diet-induced neuroinflammation and cognitive decline remain unknown. This study aimed to evaluate the neuroprotective effect and mechanism of dietary L edodes β-glucan supplementation against the obesity-associated cognitive decline in mice fed by a HF diet. Methods: C57BL/6J male mice were fed with either a lab chow (LC), HF or HF with L. edodes β-glucan supplementation diets for 7 days (acute) or 15 weeks (chronic). Cognitive behavior was examined; blood, cecum content, colon and brain were collected to evaluate metabolic parameters, endotoxin, gut microbiota, colon, and brain pathology. Results: We reported that acute L. edodes β-glucan supplementation prevented the gut microbial composition shift induced by the HF diet. Chronic L. edodes β-glucan supplementation prevented the HF diet-induced recognition memory impairment assessed by behavioral tests (the temporal order memory, novel object recognition and Y-maze tests). In the prefrontal cortex and hippocampus, the β-glucan supplementation ameliorated the alteration of synaptic ultrastructure, neuroinflammation and brain-derived neurotrophic factor (BDNF) deficits induced by HF diet. Furthermore, the β-glucan supplementation increased the mucosal thickness, upregulated the expression of tight junction protein occludin, decreased the plasma LPS level, and inhibited the proinflammatory macrophage accumulation in the colon of mice fed by HF diet. Conclusions: This study revealed that L. edodes β-glucan prevents cognitive impairments induced by the HF diet, which may occur via colon-brain axis improvement. The finding suggested that dietary L. edodes β-glucan supplementation may be an effective nutritional strategy to prevent obesity-associated cognitive decline.
... Mushrooms have been shown to have very substantial effects on cognitive function (341,348,(510)(511)(512)(513) , and this is mainly ascribed to their ERG content, that also deceases with the age of the consumer (391) . The kinds of evidence include both doubleblind, placebo-controlled clinical trials (341) and observational (cross-sectional) studies in both humans (348,(510)(511)(512) and rodents (513) . ...
... Mushrooms have been shown to have very substantial effects on cognitive function (341,348,(510)(511)(512)(513) , and this is mainly ascribed to their ERG content, that also deceases with the age of the consumer (391) . The kinds of evidence include both doubleblind, placebo-controlled clinical trials (341) and observational (cross-sectional) studies in both humans (348,(510)(511)(512) and rodents (513) . Thus, consuming 1·5 mushroom servings per week was associated with a halving of the incidence of mild cognitive impairment (a precursor of Alzheimer's dementia), while intake of nine servings per week was associated with a five-fold decrease (348) . ...
... The kinds of evidence include both doubleblind, placebo-controlled clinical trials (341) and observational (cross-sectional) studies in both humans (348,(510)(511)(512) and rodents (513) . Thus, consuming 1·5 mushroom servings per week was associated with a halving of the incidence of mild cognitive impairment (a precursor of Alzheimer's dementia), while intake of nine servings per week was associated with a five-fold decrease (348) . Note, however, that at least one mushroom trial indicated no measurable benefits in healthy young physical education students (514) . ...
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Ergothioneine (ERG) is an unusual thio-histidine betaine amino acid that has potent antioxidant activities. It is synthesised by a variety of microbes, especially fungi (including in mushroom fruiting bodies) and actinobacteria, but is not synthesised by plants and animals who acquire it via the soil and their diet, respectively. Animals have evolved a highly selective transporter for it, known as solute carrier family 22, member 4 (SLC22A4) in humans, signifying its importance, and ERG may even have the status of a vitamin. ERG accumulates differentially in various tissues, according to their expression of SLC22A4, favouring those such as erythrocytes that may be subject to oxidative stress. Mushroom or ERG consumption seems to provide significant prevention against oxidative stress in a large variety of systems. ERG seems to have strong cytoprotective status, and its concentration is lowered in a number of chronic inflammatory diseases. It has been passed as safe by regulatory agencies, and may have value as a nutraceutical and antioxidant more generally.
... This population-based cross-sectional study was conducted from Jul 2011 to Dec 2016. The study population came from the Diet and Healthy Aging Study (DaHA), a community-based longitudinal cohort study that recruited elderly participants (aged ≥60) from a western district of Singapore [29][30][31]. Well-trained nurses recruited participants via door-to-door census in the district. A demographic questionnaire, the Singapore Modified version of Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and a battery of neuropsychological tests were completed by trained research staffs [29,31]. ...
... Well-trained nurses recruited participants via door-to-door census in the district. A demographic questionnaire, the Singapore Modified version of Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and a battery of neuropsychological tests were completed by trained research staffs [29,31]. The inclusive criteria for this study were: 1) Singaporean or permanent residents who live in the West Region of Singapore and 2) aged ≥60. ...
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Mild cognitive impairment (MCI), as a preclinical phase of dementia, provides an invaluable time window for intervention. Besides several proposed modifiable risk factors, the associations of MCI with dietary habits and bowel movement are not well clarified. We thus conducted a cross-sectional study of community-living Singapore elderly and focused on the relationship of clinically diagnosed MCI with dietary habits and bowel movement frequencies. The multiple logistic regression results showed that frequent (≥4 days per week) fruit consumption (P = 0.004), active (≥4 days per week) bowel movement within 10 minutes (P = 0.027), and years of schooling were negatively associated with MCI occurrence. In contrast, medical comorbidities including hypertension, stroke, and cataract/glaucoma were found to be risk factors. Furthermore, a Bayesian network model of causal inference detected five hypothesized causal-association paths leading to MCI, namely bowel movement, stroke, years of schooling via fruit consumption, hypertension via stroke and hypertension via cataract/glaucoma. The combination of the two direct factors (inactive bowel movement and stroke) reached a maximum conditional probability of 60.00% for MCI occurrence. Taken together, this study was the first to link bowel movement with MCI occurrence. In addition, it suggested five modifiable hypothesized causal-association paths to MCI.
... Some epidemiological studies have reported associations between mushroom consumption and low risks of chronic diseases, such as cancers [16,17], metabolic syndrome [18], cognitive impairment [19], and dementia [20] although some studies failed to observe significant associations [21][22][23][24][25]. However, whether the consumption of mushrooms is associated with better survival and low risk of premature mortality remains uncertain using large-scale epidemiologic studies. ...
... A study conducted by Zhang and colleagues showed that greater mushroom consumption was associated with a lower risk of dementia in elderly Japanese [20]. Furthermore, a study conducted in Singapore showed that mushroom intake was associated with lower odds of mild cognitive impairment [19]. However, several other epidemiological studies yield non-significant associations [21][22][23][24][25]. Furthermore, a previous systematic review and meta-analysis of fruit and vegetable intake and risk of mortality using 2 studies found no association between mushroom consumption and all-cause mortality [26]. ...
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Background Whether mushroom consumption, which is rich in several bioactive compounds, including the crucial antioxidants ergothioneine and glutathione, is inversely associated with low all-cause and cause-specific mortality remains uncertain. This study aimed to prospectively investigate the association between mushroom consumption and all-cause and cause-specific mortality risk. Methods Longitudinal analyses of participants from the Third National Health and Nutrition Examination Survey (NHANES III) extant data (1988–1994). Mushroom intake was assessed by a single 24-h dietary recall using the US Department of Agriculture food codes for recipe foods. All-cause and cause-specific mortality were assessed in all participants linked to the National Death Index mortality data (1988–2015). We used Cox proportional hazards regression models to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause and cause-specific mortality. Results Among 15,546 participants included in the current analysis, the mean (SE) age was 44.3 (0.5) years. During a mean (SD) follow-up duration of 19.5 (7.4) years , a total of 5826 deaths were documented. Participants who reported consuming mushrooms had lower risk of all-cause mortality compared with those without mushroom intake (adjusted hazard ratio (HR) = 0.84; 95% CI: 0.73–0.98) after adjusting for demographic, major lifestyle factors, overall diet quality, and other dietary factors including total energy. When cause-specific mortality was examined, we did not observe any statistically significant associations with mushroom consumption. Consuming 1-serving of mushrooms per day instead of 1-serving of processed or red meats was associated with lower risk of all-cause mortality (adjusted HR = 0.65; 95% CI: 0.50–0.84). We also observed a dose-response relationship between higher mushroom consumption and lower risk of all-cause mortality (P-trend = 0.03). Conclusion Mushroom consumption was associated with a lower risk of total mortality in this nationally representative sample of US adults.
... A unique feature of ERGO compared to other antioxidants is that its distribution to the brain parenchyma is independent of the BBB, but rather mediated by OCTN1 receptors. Thus, it seems reasonably certain that there is a huge interest in assessing the protective role of ERGO in the brain 15,23,29 , particularly oxidative stress related to Alzheimer's disease [40][41][42] . In www.nature.com/scientificreports/ ...
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Ergothioneine (ERGO) is a rare amino acid mostly found in fungi, including mushrooms, with recognized antioxidant activity to protect tissues from damage by reactive oxygen species (ROS) components. Prior to this publication, the biodistribution of ERGO has been performed solely in vitro using extracted tissues. The aim of this study was to develop a feasible chemistry for the synthesis of an ERGO PET radioligand, [11C]ERGO, to facilitate in vivo study. The radioligand probe was synthesized with identical structure to ERGO by employing an orthogonal protection/deprotection approach. [11C]methylation of the precursor was performed via [11C]CH3OTf to provide [11C]ERGO radioligand. The [11C]ERGO was isolated by RP-HPLC with a molar activity of 690 TBq/mmol. To demonstrate the biodistribution of the radioligand, we administered approximately 37 MBq/0.1 mL in 5XFAD mice, a mouse model of Alzheimer’s disease via the tail vein. The distribution of ERGO in the brain was monitored using 90-min dynamic PET scans. The delivery and specific retention of [11C]ERGO in an LPS-mediated neuroinflammation mouse model was also demonstrated. For the pharmacokinetic study, the concentration of the compound in the serum started to decrease 10 min after injection while starting to distribute in other peripheral tissues. In particular, a significant amount of the compound was found in the eyes and small intestine. The radioligand was also distributed in several regions of the brain of 5XFAD mice, and the signal remained strong 30 min post-injection. This is the first time the biodistribution of this antioxidant and rare amino acid has been demonstrated in a preclinical mouse model in a highly sensitive and non-invasive manner.
... Several studies investigated the putative health benefits of mushroom consumption. These include the association of increased mushroom consumption with decreased risks of dementia [133,134], cardiovascular disease, certain cancers (e.g. prostate and breast cancer) [135,136], IBD [137], metabolic syndrome [138], PD and other neurological disorders [139], viral infections [140] and many other conditions. ...
Article
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There has been a recent surge of interest in the unique low molecular weight dietary thiol/thione, ergothioneine. This compound can accumulate at high levels in the body from diet and may play important physiological roles in human health and development, and possibly in prevention and treatment of disease. Blood levels of ergothioneine decline with age and onset of various diseases. Here we highlight recent advances in our knowledge of ergothioneine.
... Alzheimer's disease [222]. Mushrooms contain many other substances whose exact role in brain health is not yet clear. ...
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In Sub-Saharan Africa, despite poverty, chronic hunger and food insecurity, traditional eating has been related to positive health outcomes and sustainability. There is little health research on diet quality based on what African people consume. The defining characteristics of the traditional African cuisine are the richness in herbs and spices, fermented foods and beverages, and healthy and whole ingredients used. However, as countries in this region become more economically developed, there is a shift to “modern” occidental foods rich in saturated fats, sugar and sweeteners. As a result, there are increased incidences of previously unreported ailments due to unbalanced diet. The regular practice of infinite international aid to the region to curb food insecurity has been unsustainable, ineffective and with no end in sight. Local increase in production and productivity is imperative. Protein rich foods in dietary guidelines enhance only those of animal or plant sources while rich protein sources such of mushroom, has been absent in these charts. This article considers the valorisation of traditional African foods and the importance of establishing an African Food-Based Dietary Guidelines (AFBDGs), an unprecedented Food Pyramid, along with the added emphasis on the potential of African mushrooms, which may play a role in shielding Sub-Saharan Africans against the side-effects of a western stylish diet and promote health. It enhances the preventive role of mushrooms in viral diseases and other disorders.
... People who incorporate mushrooms into their diets, even in small amounts (more than twice a week), seem to have a lower risk of mild cognitive impairment, usually preceding Alzheimer's disease [196]. Mushrooms contain many other substances whose exact role in brain health is not yet clear, but they include hericenones, erinacines terpenoids, scabronines, isoindolinones, sterols, and dictyophorines, which are a series of compounds that could contribute to the growth of nerve and brain cells [197]. ...
Article
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The defining characteristics of the traditional Sub-Saharan Africa (SSA) cuisine have been the richness in indigenous foods and ingredients, herbs and spices, fermented foods and beverages, and healthy and whole ingredients used. It is crucial to safeguard the recognized benefits of mainstream traditional foods and ingredients, which gradually eroded in the last decades. Notwithstanding poverty, chronic hunger, malnutrition, and undernourishment in the region, traditional eating habits have been related to positive health outcomes and sustainability. The research prevailed dealing with food availability and access rather than the health, nutrition, and diet quality dimensions of food security based on what people consume per country and on the missing data related to nutrient composition of indigenous foods. As countries become more economically developed, they shift to “modern” occidental foods rich in saturated fats, salt, sugar, fizzy beverages, and sweeteners. As a result, there are increased incidences of previously unreported ailments due to an unbalanced diet. Protein-rich foods in dietary guidelines enhance only those of animal or plant sources, while rich protein sources such as mushrooms have been absent in these charts, even in developed countries. This article considers the valorization of traditional African foodstuffs and ingredients, enhancing the importance of establishing food-based dietary guidelines per country. The crux of this review highlights the potential of mushrooms, namely some underutilized in the SSA, which is the continent’s little exploited gold mine as one of the greatest untapped resources for feeding and providing income for Africa’s growing population, which could play a role in shielding Sub-Saharan Africans against the side effects of an unhealthy stylish diet.
... With an increased prevalence or incidence of MCI in Chinesespeaking populations around the world (approximately 14% prevalence of MCI in aged 60 years or older; Feng et al., 2019;Vanoh et al., 2017), it is of great importance to have a Chinese version of questionnaire inquiring SCD in MCI to study MCI in the Chinese communities. Based on such need, we translated the SCD-Q21 (see details in Supplementary Material S2). ...
Article
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Background Subjective cognitive decline‐questionnaire 9 (SCD‐Q9) was developed to detect SCD complaints at risk of mild cognitive impairment (MCI). However, our previous findings indicated that its coverage might be insufficient. To test this hypothesis, we recently translated SCD‐Q21. Objective To examine the reliability and validity of this translated SCD‐Q21 and to explore its effectiveness for discriminating MCI from controls. Methods Item analysis was performed to understand its item discrimination and homogeneity. The Cronbach's α and Spearman‐Brown's split‐half coefficients were calculated to test its reliability. The Kaiser–Meyer–Olkin (KMO) value, Bartlett's sphericity test, and exploratory factor analysis (EFA) were used to examine its construct validity. The content validity was evaluated using five‐grade Likert scale. Finally, the SCD‐Q21 scores in MCI and controls were compared. Results The difference of each item between the extreme groups was significant. The Cronbach's α coefficient was .913 and Spearman‐Brown's split‐half coefficient was .894. When performing holding one‐out approach, the Cronbach's α coefficient ranged from .906 to .914. The KMO value was .929 and the difference of Bartlett's Sphericity test was significant. All experts scored 5 points when assessing its content. Finally, a significant difference of score was found between MCI and NC groups. Conclusions The reliability and validity of the SCD‐Q21 are good, which may pave a way for its application in a wider Chinese‐speaking population.
... They have been considered a "forgotten source of nutrients" [29], making it hard to calculate their actual consumption and contribution to human health. Despite this limitation, accumulating evidence suggests that mushroom consumption may be associated with a lower risk of chronic diseases, including cancers [30], metabolic syndrome, [22] cognitive impairment, [31,32], and dementia [33]. A few epidemiological observational studies also have reported an inverse association between mushroom consumption and the risk of mortality [34,35]. ...
Article
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Background Whether mushroom consumption, which is a rich source of potent antioxidants ergothioneine and glutathione, vitamins, and minerals (e.g., selenium & copper), is associated with a lower mortality risk is not well understood. This study aimed to examine the association between mushroom consumption and risk of mortality in a prospective cohort study and a meta-analysis of prospective cohort studies. Methods We followed 30,378 participants from the continuous National Health and Nutrition Examination Survey (NHANES) extant data (2003-2014). Dietary mushroom intake was assessed using up to two 24-h recalls. Mortality was evaluated in all participants linked to the National Death Index mortality data through December 31, 2015. We used Cox proportional hazards regression models to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). We also conducted a meta-analysis, including results from our present study and 4 other cohort studies. Results During a mean (SD) of 6.7 (3.4) years of follow-up, a total of 2855 death cases were documented among NHANES participants. In our analysis of continuous NHANES, we found a non-significant association between mushroom consumption and all-cause mortality (adjusted hazard ratio (HR) = 0.84; 95% CI: 0.67-1.06) after adjusting for demographic, major lifestyle factors, overall diet quality, and other dietary factors, including total energy. The meta-analysis of prospective cohort studies, including 601,893 individuals, showed that mushroom consumption was associated with a lower risk of all-cause mortality (pooled risk ratio: 0.94; 95% CI: 0.91, 0.98). Conclusion In a meta-analysis of prospective cohort studies, mushroom consumption was associated with a lower risk of all-cause mortality.
... In 2019, a community-based cross-sectional study was conducted on 663 participants aged ≥60 years from the Diet and Healthy Aging study in Singapore (Feng et al., 2019). Individuals consuming >2 portions of mushrooms per week had reduced risk of mild cognitive impairment in the multiple-adjusted logistic regression model (OR: 0.48; 95%CI 0.26-0.89; ...
Article
Background mushrooms are traditionally used as a food ingredient and in folk medicine. Many in vitro and animal studies have reported their potential health effects, but without any clear application in human health. Although they have a worldwide history of use in dishes and folk medicine, mushroom extracts are commonly taken as supplements but need to be evaluated regarding clinical effects and safety, in particular among patients searching for further efficacy for their disease beside pharmacological treatments already prescribed. Scope and approach this review summarizes available data from the scientific literature about the nutritional and effects of mushrooms on human health by selecting clinical studies on humans in English. At the same time, the safety profile and unwanted effects were highlighted. Key findings and conclusions in spite of their wide use among populations, data on humans were scant and did not justify extensive use without more well-designed trials on mushroom efficacy. Overall, their use seems to be safe, but with some side effects, easily reversible after intake interruption. Nutritional use seems promising for coping with the energy surplus of the Western countries and could be useful for some nutritional aspects.
... In a recent study, the lifestyle of 633 Chinese seniors living in Singapore between 2011 and 2017 was analyzed, and it was revealed that various mushrooms have therapeutic effects in combatting AD by exerting neuroprotective and antioxidant effects (Feng et al., 2019). Mushrooms and their extracts have been well-known for their nutritional and culinary values, which may be regarded as novel nature-based nutraceuticals to mitigate AD and other age-related neurodegenerative disorders. ...
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Objective To investigate the efficacy and safety of three H. erinaceus mycelia (EAHE) capsules (350 mg/capsule; containing 5 mg/g erinacine A active ingredient) per day for the treatment of patients with mild Alzheimer’s Disease (AD).Methods This study comprised a 3-week no-drug screening period, followed by a 49-week double-blind treatment period with 2-parallel groups in which eligible patients were randomized to either three 5 mg/g EAHE mycelia capsules per day or identical appearing placebo capsules. Cognitive assessments, ophthalmic examinations, biomarker collection, and neuroimaging were followed throughout the study period.ResultsAfter 49 weeks of EAHE intervention, a significant decrease in Cognitive Abilities Screening Instrument score was noted in the placebo group, a significant improvement in Mini-Mental State Examination score was observed in the EAHE group and a significant Instrumental Activities of Daily Living score difference were found between the two groups. In addition, EAHE group achieved a significantly better contrast sensitivity when compared to the placebo group. Moreover, only the placebo group observed significantly lowered biomarkers such as calcium, albumin, apolipoprotein E4, hemoglobin, and brain-derived neurotrophic factor and significantly elevated alpha1-antichymotrypsin and amyloid-beta peptide 1–40 over the study period. Using diffusion tensor imaging, the mean apparent diffusion coefficient (ADC) values from the arcuate fasciculus region in the dominant hemisphere significantly increased in the placebo group while no significant difference was found in the EAHE group in comparison to their baselines. Moreover, ADC values from the parahippocampal cingulum region in the dominant hemisphere significantly decreased in the EAHE group whereas no significant difference was found in the placebo group when compared to their baselines. Lastly, except for four subjects who dropped out of the study due to abdominal discomfort, nausea, and skin rash, no other adverse events were reported.Conclusion Three 350 mg/g EAHE capsules intervention for 49 weeks demonstrated higher CASI, MMSE, and IADL scores and achieved a better contrast sensitivity in patients with mild AD when compared to the placebo group, suggesting that EAHE is safe, well-tolerated, and may be important in achieving neurocognitive benefits.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT04065061.
... Examination of mushroom consumption found reverse association with the odds of having MCI. Participants who consumed mushrooms >2 portions per week had reduced odds of having MCI than those who consumed mushrooms less than once per week [28]. In examination of dietary habits, participants with frequent (≥4 days per week) fruit consumption and active (≥4 days per week) bowel movement within 10 minutes were negatively associated with MCI occurrence [29]. ...
Article
How diet is related with cognition and health has not been systematically examined in Asians whose eating habits are very different from their counterparts in the West and the biological mechanisms underlying such www.aging-us.com 2 AGING links are not well known yet. The diet and healthy aging (DaHA) study is a community-based longitudinal study conducted to examine the role of diet and nutrition in promoting cognitive, emotional, and physical health among community-living elderly Singaporeans. The first wave of DaHA, conducted from 2011 to 2017, provided detailed information on diet and baseline cognitive function and health from 1010 community-living elderly in Singapore. Biomarkers of oxidative stress, systemic inflammation, and genetic information were collected. The ongoing second wave of DaHA is conducted from 2017 to 2020, which provides follow-up assessments using established cognitive tests and clinical tools. This well-characterized cohort, with its archived biological samples and high-quality data on diet and lifestyle factors will allow researchers to explore the relationships among diet, nutrition, genes, cognition, mental and physical health in an extremely cost-effective manner. Translations of the research findings into clinical and public health practices will potentially help to promote cognitive health at the population level and reduce healthcare costs related to cognitive impairment.
... In humans, the enhancement effects on cognitive function associated with an increase in mushroom consumption evidenced the crucial role of ergothioneine in the brain. 78 Several studies demonstrated that this compound could promote neurogenesis and act against oxidative damage and neuroinflammation. 72,79−81 The precise role of selenoneine in this organ is not known so far. ...
... However, it is worth specifying that the aforementioned meta-analysis mostly considered patients with a diagnosed depression, while we opted for a brief screening tool, i.e., the Geriatric Depression Scale (GDS), for excluding major depression. The same can be noted for other well-known reliable protective/risk factors against/favoring developing MCI and dementia, such as, physical activity, smoking, alcohol consumption, and BMI, e.g., [69][70][71][72]. Regarding physical activity, we can speculate that the use of a single item, as in this study, may be insufficiently sensitive in capturing the variability within habits among our study participants. ...
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Mild Cognitive Impairment (MCI) is a transition stage between normal aging and dementia and can be useful to monitor the cognitive status of people at risk of dementias. Our aims were to investigate the prevalence of amnestic and non-amnestic MCI in a South Italian elderly population, and to identify socio-demographic, clinical and lifestyle factors associated with MCI. A cross-sectional retrospective population study on 839 community-dwelling participants over 60 years of age was carried out. Elderly people were administered a brief neuropsychological screening to identify their cognitive and functional status, and a questionnaire to investigate several socio-demographic, clinical, and lifestyle factors. Prevalence estimate for MCI was 12.0% (95% CI: 10.0–14.5%), for amnestic MCI was 7.4% (95% CI: 5.8–9.4%), and for non-amnestic MCI was 4.6% (95% CI: 3.4–6.4%), for people older than 60 years of age. Logistic regression models, corrected for age, sex, and education, revealed a significant association of MCI with the following factors: age, education, intellectual activities, and topographical disorientation. On the other hand, education, clinical factors (e.g., depression level and perceived physical pain), lifestyle factors (e.g., smoking, alcohol, and leisure/productive activities), dietary habits, quality of life, and self-reported topographical disorientation were non-significantly associated with MCI. Prevalence estimates and the association of MCI and its subtypes with risk and protective factors were discussed in comparison with the most recent systematic reviews and meta-analyses.
... EGT has been found to promote the proliferation and differentiation of neuronal cells and relieve depressive symptoms in mice at a reasonable daily intake level (120 mg EGT/100 g diet) (Nakamichi et al., 2016). Recently, a communitybased cross-sectional in Singapore also found that eating mushrooms (more than 2 times a week) contributes to improving the cognitive level and extending the life of patients (Feng et al., 2019). However, in the elderly, especially in patients with neurodegenerative diseases, the level of EGT is significantly decreased in the brain and plasma (Cheah et al., 2016a). ...
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L-Ergothioneine (EGT) is a natural antioxidant derived from microorganisms, especially in edible mushrooms. EGT is found to be highly accumulated in tissues that are susceptible to oxidative damage, and it has attracted extensive attention due to its powerful antioxidant activity and the tight relationships of this natural product with various oxidative stress-related diseases. Herein, we 1) introduce the biological source and in vivo distribution of EGT; 2) review the currently available evidence concerning the relationships of EGT with diabetes, ischemia-reperfusion injury-related diseases like cardiovascular diseases and liver diseases, neurodegenerative diseases, and other diseases pathogenically associated with oxidative stress; 3) summarize the potential action mechanisms of EGT against these diseases; 4) discuss the advantages of EGT over other antioxidants; and 5) also propose several future research perspectives for EGT. These may help to promote the future application of this attractive natural antioxidant.
... Accumulating research has provided evidence for the protective effects of mushrooms and cereal against various chronic diseases and neurodegeneration disorders. A community-based crosssectional study in Singapore demonstrates that participants who consumed mushrooms >2 portions per week have a reduced risk of mild cognitive impairment (17). Breakfast cereal consumption by children and adolescence is associated with greater cognitive performance (18,19). ...
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... Participants from the study group showed a significantly better performance in cognitive function tests than participants from the placebo group after 16 weeks of therapy. Additionally, a survey of Singaporean residents showed an association between the amount of mushroom consumption and the incidence of age-related conditions, such as dementia or MCI [166], once again suggesting that the mushrooms contain a significant number of compounds that have the ability to slow the deterioration of cognitive functions. ...
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... Indeed, ET has many neuroprotective properties [4,5,18,26,27], as reviewed in detail in this special issue [18,25,26]. Consistent with a key protective role of ET against the development of age-related diseases, higher dietary consumption of mushrooms, a rich source of ET [9], is associated with lower disease risk [28][29][30][31]. ...
... The WFPB diet essentially consists of vegetables, whole grains, legumes, fruits, nuts and seeds, without restricting energy intake (see table 5). In addition, the regular consumption of specific foods Open access that have the potential to beneficially influence cognitive functions, based on current clinical evidence, is encouraged (eg, green leafy vegetables, 38 mushrooms, 39 citrus fruits, 40 soy products, 41 blueberries, 42 nuts, 43 turmeric, 44 green tea 45 and omega-3 fatty acids 46 ). Participants are instructed to exclude animal products from their diets because of the proinflammatory potential of animal products and to refrain from consuming highly processed foods. ...
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Introduction Ageing is associated with a multitude of healthcare issues including dementia, depression, frailty, morbidity associated with chronic disease and high healthcare utilisation. With Singapore’s population projected to age significantly over the next two decades, it has become increasingly important to understand the disease burden and etiological process among older adults. The Community Health and Intergenerational study aims to holistically examine ageing in place by investigating the resilience and vulnerability factors of the ageing process in the biological, psychological and social domains within the environment. Methods and analysis Using a cohort multiple randomised controlled trial design, comprehensive health profiles of community-dwelling older adults will be collected. The objective is to recruit 1000 participants (aged 60–99 years) living in the western region of Singapore within a period of 3 years (2018–2020). Assessments include basic sociodemographic, physical health and function (cardiac, oral and blood profiles and visual function), cognitive functioning, daily functioning, physical fitness, emotional state, free-flowing speech, sleep quality, social connectedness, caregiver burden, intergenerational communication, quality of life, life satisfaction, attitudes to ageing and gratitude and compassion. Results from the cohort will enable future studies to identify at-risk groups and develop interventions to improve the physical and mental health and quality of life of older adults. Ethics and dissemination Approval of the cohort study by the National University of Singapore Institutional Review Board (NUS-IRB Reference code: H-17-047) was obtained on 12 October 2017. Written consent will be obtained from all participants. Findings from the cohort study will be disseminated by publication of peer-reviewed manuscripts, presentations at scientific meetings and conferences with local stakeholders.
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Chapter
Substantial studies have suggested that natural compounds rich in antioxidants can enhance the immune system and decrease oxidative stress. These substances facilitate in scavenging the reactive species that initiate the peroxidation, inhibit the formation of peroxides, breaking the autoxidative chain reaction, and quenching •O2⁻. The molecules with antioxidants properties such as low molecular weight antioxidant, glutathione, polyphenol, carotenoids, minerals, ascorbic acid, vitamin E, ubiquinone, organosulfur compounds, ergothioneine, betalains, and carnosine/anserine have demonstrated their potential in the alleviation of age-related diseases. However, the exact molecular mechanisms of these molecules involved in the prevention of age-related diseases are worth discussing further. In this chapter, we discussed the biological mechanism of molecules with antioxidant activity against age-related diseases. Overall, a better understanding of the mode of action of antioxidants involved in the redox imbalance in age-related diseases would provide a useful approach in mediating diseases.
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Ergothioneine (ERGO) is a potent antioxidant and anti-inflammatory amino acid that is highly bioavailable to humans from the diet. ERGO is now regarded by some as a "longevity vitamin" that has the potential to mitigate some chronic diseases of aging and thereby increase life expectancy when present in adequate amounts. However, only limited knowledge exists regarding ERGO content in the human diet. Since ERGO is produced primarily by fungi, mushrooms are known to be the leading dietary source, but ERGO is found in relatively low amounts throughout the food chain as a result of soil-borne fungi or bacteria passing it on to plants through their roots. Some conventional agricultural practices that negatively impact soil fungi, such as excessive soil disturbance (plowing), can significantly reduce ERGO content of food crops when compared to regenerative practices such as eliminating tillage of the soil (No-Till). This has led us to the concept that ERGO may be a definitive connection between soil health and human health.
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Chapter
Memory is the ability of an individual to record the information and recall it whenever needed. A complex network of numerous nerve cells and cortex of brain helps us to store memory captured in the form of words/pictures/olfactory signals, etc. Hippocampus helps in converting short form of memory into long term. By continuous learning we memorize the things and in an accident or disease there is loss of memory, stress and anxiety can lead to depression and ill health. Just like herbs (i.e. tea—Camellia sinensis (L.) Kuntze) stimulates the nerves of our brain the use of certain mushrooms like Hericium, Ganoderma, Lentinula, Psilocybe helps in brain-boosting and cognitive impairments. Mushrooms and their bioactive compounds present in the mycelial extract help in lowering the blood pressure, change the mood and control the progression of Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Stressful conditions are often associated with loss of memory and other cognitive functions, which may lead to threats of schizophrenia and Alzheimer’s disease. In traditional or alternative system of medicine, numerous plants and fungi have been used to alleviate memory impairment both in healthy individuals and those with disease states which are now recognized as specific cognitive disorders. An ethno-mycological approach has provided leads to identify mushrooms and their bioactive compoundsBioactive compounds that may have potential to modulate cognitive abilities by different modes of action. A variety of therapeutic targets have been identified as relevant in the treatment of cognitive disorders, and neuroprotection against glutamate-induced overstimulation of N-methyl-d-aspartate (NMDA) receptors, by the use of NMDA receptor modulators. Other activities considered to be relevant in the alleviation of cognitive impairmentCognitive impairments include anti-inflammatory, antioxidantAntioxidants and estrogenic activities. Psychedelics produced by hallucinogenic mushrooms can cause physical changes in brain, even to the cellular as well as molecular levels, which is the primary component. These psychedelics when exposed to neuron cells help to create new outgrowths of the neuron network in the brain. These new connections help in brain functioning. Proactive compounds like hericenones (from mushroom) and erinacines (from mycelium) of lion’s mane, cordycepin from CordycepsCordyceps, lentinan from Lentinula help in stress alleviation, induce sound sleep and enhance the memory by stimulating the brain and avoiding shrinking of neurons in the cortex.
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Ergothioneine is a sulfur‐containing histidine derivative that emerges from microbial biosynthesis and enters the human body via intestinal uptake and regulated distribution into specific tissues. While the proteins involved in biosynthesis and uptake are well characterized, less is known about the degradative pathways of ergothioneine. In this report we describe the crystal structure of the active form of ergothionase from the oral pathogen Treponema denticola in complex with the substrate analog desmethyl‐ergothioneine sulfonic acid. This enzyme catalyzes 1,2‐elimination of trimethylamine from ergothioneine and its oxidation product ergothioneine sulfonic acid using a unique mode of substrate activation combined with acid/base catalysis. This structural and mechanistic investigation revealed four essential catalytic residues that are strictly conserved in homologous proteins from common gastrointestinal bacteria and numerous pathogenic bacteria, suggesting that bacterial activity may play an important role in determining the availability of ergothioneine in healthy and diseased human tissue.
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Ergothioneine is a thiol/thione molecule synthesised only by some fungi and bacteria. Nonetheless, it is avidly taken up from the diet by humans and other animals through a transporter, OCTN1, and accumulates to high levels in certain tissues. Ergothioneine is not rapidly metabolised or excreted in urine and is present in many, if not all, human tissues and body fluids. Ergothioneine has powerful antioxidant and cytoprotective properties in vitro and there is evidence that the body may concentrate it at sites of tissue injury by raising OCTN1 levels. Decreased blood and/or plasma levels of ergothioneine have been observed in some diseases suggesting that a deficiency could be relevant to the disease onset or progression. This brief Review explores the possible roles of ergothioneine in human health and disease. This article is protected by copyright. All rights reserved.
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The candidate vitamin ergothioneine (ET) is a unique antioxidant. Expression of the ergothioneine transporter (ETT) (gene symbol SLC22A4) in distinct cells is thought to signal intracellular ET activity, since we have previously shown that the ETT is highly selective for ET. Unfortunately, some continue to hold the ETT as a relevant drug transporter, using the misleading functional name OCTN1, novel organic cation transporter. The present study was provoked by 2 recent reports in which new ETT substrates were declared. Astonishingly, the transport efficiencies (TE) of ETT for saracatinib and some nucleoside drugs were as high as the TE for ET. Here we examined, based on regulated expression of ETT from human and rat in 293 cells and liquid chromatography-mass spectrometry quantification, the transport of several drugs. With the nucleosides cytarabine, gemcitabine, 2'-deoxycytidine, and 2'-deoxyadenosine, and the drugs saracatinib, ipratropium, metformin, and oxaliplatin, the uptake into cells expressing ETT was not increased over control cells. ETT-mediated uptake of gabapentin was detectable, but the TE was approximately 100-fold lower than the TE for ergothioneine (50 to 200 μl min-1 mg protein-1). In conclusion, the ETT remains highly specific for its physiological substrate ergothioneine. Our results contradict several reports on additional substrates. The ETT does not provide multiple substrate specificities and it is not a transporter of cationic drugs. Only compounds that are related to ET in substructure - for example gabapentin, carnitine, and tetraethylammonium - can be transported, but with very low efficiency. Thus, ETT persists as a specific molecular indicator of ET activity.
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L-ergothioneine (ET) is a diet-derived amino acid that accumulates at high concentrations in animals and humans. Numerous studies have highlighted its antioxidant abilities in vitro, and possible cytoprotective capabilities in vivo. We investigated the uptake and distribution of ET in various organs by a highly sensitive and specific liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) technique, both before and after oral administration of pure ET (35 and 70 mg/kg/day for 1, 7, and 28 days) to male C57BL6J mice. ET primarily concentrates in the liver and whole blood, and also in spleen, kidney, lung, heart, intestines, eye, and brain tissues. Strong correlations were found between ET and its putative metabolites - hercynine, ET-sulfonate (ET-SO3H), and S-methyl ET. Hercynine accumulates in the brain after prolonged ET administration. This study demonstrates the uptake and distribution of ET and provides a foundation for future studies with ET to target oxidative damage in a range of tissues in human diseases.
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Aim: We investigated the uptake and pharmacokinetics of ergothioneine (ET), a dietary thione with free radical scavenging and cytoprotective capabilities, after oral administration to humans, and its effect on biomarkers of oxidative damage and inflammation. Results: Following oral administration, ET is avidly absorbed and retained by the body with significant elevations in plasma and whole blood concentrations, and relatively low urinary excretion (less than 4% of administered ET). ET levels in whole blood were highly correlated to levels of hercynine and S-methyl-ergothioneine, suggesting that they may be metabolites. After ET administration, some decreasing trends were seen on biomarkers of oxidative damage and inflammation, including allantoin (urate oxidation), 8-hydroxy-2-deoxyguanosine (DNA damage), 8-iso-PGF2α (lipid peroxidation), protein carbonylation, and C-reactive protein. However, most of the changes were non-significant. Innovation: This is the first study investigating the administration of pure ET to healthy human volunteers, and monitoring its uptake and pharmacokinetics. This compound is rapidly gaining attention due to its unique properties, and this study lays the foundation for future studies. Conclusion: The uptake and retention of ET by the body suggests an important physiological function. The decreasing trend of oxidative damage biomarkers is consistent with animal studies suggesting that ET may function as a major antioxidant but perhaps only under conditions of oxidative stress.
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Abstract Mushrooms have long been used not only as food but also for the treatment of various ailments. Although at its infancy, accumulated evidence suggested that culinary-medicinal mushrooms may play an important role in the prevention of many age-associated neurological dysfunctions, including Alzheimer's and Parkinson's diseases. Therefore, efforts have been devoted to a search for more mushroom species that may improve memory and cognition functions. Such mushrooms include Hericium erinaceus, Ganoderma lucidum, Sarcodon spp., Antrodia camphorata, Pleurotus giganteus, Lignosus rhinocerotis, Grifola frondosa, and many more. Here, we review over 20 different brain-improving culinary-medicinal mushrooms and at least 80 different bioactive secondary metabolites isolated from them. The mushrooms (either extracts from basidiocarps/mycelia or isolated compounds) reduced beta amyloid-induced neurotoxicity and had anti-acetylcholinesterase, neurite outgrowth stimulation, nerve growth factor (NGF) synthesis, neuroprotective, antioxidant, and anti-(neuro)inflammatory effects. The in vitro and in vivo studies on the molecular mechanisms responsible for the bioactive effects of mushrooms are also discussed. Mushrooms can be considered as useful therapeutic agents in the management and/or treatment of neurodegeneration diseases. However, this review focuses on in vitro evidence and clinical trials with humans are needed.
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This study aimed to determine the stratified normative data by age and education for a modified version of the Mini-Mental State Examination (MMSE) test from a large sample of community-dwelling Chinese older adults in Singapore, and to examine the MMSE's value in detecting early cognitive impairment. We studied 1,763 Chinese older adults with normal cognitive function and 121 Chinese older adults with early cognitive impairment (Clinical Dementia Rating global score 0.5). Normative MMSE values were derived for each of the 15 strata classified by age (three groups) and education level (five groups). Receiver operating characteristic curve analysis was conducted for the whole sample and each of the three education subgroups (no education, primary, secondary and above). Education level and age significantly influenced the normative values of MMSE total scores in Chinese older adults with normal cognitive function. For the purpose of detecting early cognitive impairment, an optimal balance between sensitivity (Se) and specificity (Sp) was obtained at a cutoff score of 25, 27 and 29 for each of the three education groups, respectively. For the whole sample, the optimal cutoff point was 26 (Se 0.61, Sp 0.84, area under curve 0.78). Age and education level must be taken into account in the interpretation of optimal cutoffs for the MMSE. Although widely used, the MMSE has limited value in detecting early cognitive impairment; tests with better performance should be considered in clinical practice.
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Neuropsychological testing is key to diagnosing and assessing for dementia but there is a dearth of normative neuropsychological data for ethnic Chinese older persons, particularly for non-English-speaking individuals with low education. The aim of this study was to establish a set of age-specific, education-specific, and culture-appropriate norms on measures of cognitive function for a population of cognitively normal community-dwelling Chinese elderly, and explore the effects of age and education on test performance. Results showed decreasing test performances with increasing age and very poor performance in the most poorly educated strata. However, the age-associated decline in test performance was not uniform across different education groups, indicating a more complex association. The present findings highlight a need for normative data that are applicable to lower educated elderly people as this group makes up a substantial proportion of the Asian elderly.
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To postpone cognitive decline and dementia in old age, primary prevention is required earlier in life during middle age. Dietary components may be modifiable determinants of mental performance. In the present study, habitual fruit and vegetable intake was studied in association with cognitive function and cognitive decline during middle age. In the Doetinchem Cohort Study, 2613 men and women aged 43-70 years at baseline (1995-2002) were examined for cognitive function twice, with a 5-year time interval. Global cognitive function and the domains memory, information processing speed and cognitive flexibility were assessed. Dietary intake was assessed with a semi-quantitative FFQ. In multivariate linear regression analyses, habitual fruit and vegetable intake was studied in association with baseline and change in cognitive function. Higher reported vegetable intake was associated with lower information processing speed (P = 0·02) and worse cognitive flexibility (P = 0·03) at baseline, but with smaller decline in information processing speed (P < 0·01) and global cognitive function (P = 0·02) at follow-up. Total intakes of fruits, legumes and juices were not associated with baseline or change in cognitive function. High intakes of some subgroups of fruits and vegetables (i.e. nuts, cabbage and root vegetables) were associated with better cognitive function at baseline and/or smaller decline in cognitive domains. In conclusion, total intake of fruits and vegetables was not or inconsistently associated with cognitive function and cognitive decline. A high habitual consumption of some specific fruits and vegetables may diminish age-related cognitive decline in middle-aged individuals. Further research is needed to verify these findings before recommendations can be made.
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Fruits and vegetables are among the most nutritious and healthy of foods, and are related to the prevention of many chronic diseases. The aim of the study was to examine the relationship between intake of different plant foods and cognitive performance in elderly individuals in a cross-sectional study. Two thousand and thirty-one elderly subjects (aged 70-74 years; 55% women) recruited from the general population in Western Norway underwent extensive cognitive testing and completed a comprehensive FFQ. The cognitive test battery covered several domains (Kendrick Object Learning Test, Trail Making Test--part A, modified versions of the Digit Symbol Test, Block Design, Mini-Mental State Examination and Controlled Oral Word Association Test). A validated and self-reported FFQ was used to assess habitual food intake. Subjects with intakes of >10th percentile of fruits, vegetables, grain products and mushrooms performed significantly better in cognitive tests than those with very low or no intake. The associations were strongest between cognition and the combined intake of fruits and vegetables, with a marked dose-dependent relationship up to about 500 g/d. The dose-related increase of intakes of grain products and potatoes reached a plateau at about 100-150 g/d, levelling off or decreasing thereafter, whereas the associations were linear for mushrooms. For individual plant foods, the positive cognitive associations of carrots, cruciferous vegetables, citrus fruits and high-fibre bread were most pronounced. The only negative cognitive association was with increased intake of white bread. In the elderly, a diet rich in plant foods is associated with better performance in several cognitive abilities in a dose-dependent manner.
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The relation between vitamin B-12 and cognitive function in older adults is unclear. Limited evidence suggests that the relation is modulated by apolipoprotein E epsilon4. Hence, it is important to further examine this gene-nutrient interaction. The aim was to investigate the role of apolipoprotein E (APOE) epsilon4 as a genetic predisposing factor modulating the effect of vitamin B-12 on cognitive function. A battery of neuropsychological tests, including the Mini-Mental State Examination (MMSE) for global cognition, was administered at the baseline assessment to 539 Chinese adults aged > or =55 y. The MMSE was repeated at a median 18 mo (n = 376) and a median of 38 mo (n = 247) after baseline. The interaction of vitamin B-12 and APOE epsilon4 on cognitive function was examined in a linear mixed-effects model for MMSE and in a multiple linear regression model for neuropsychological test scores. APOE epsilon4 was associated with a lower MMSE score. Vitamin B-12 (natural log transformed) was positively related to MMSE score, and this association was much stronger in APOE epsilon4 carriers than in APOE epsilon4 noncarriers (P for interaction = 0.016). Significant interactions between natural log-transformed vitamin B-12 and APOE epsilon4 were also found for the Digit Span Backward Longest Sequence (P for interaction = 0.013) and Rey Auditory Verbal Learning Test immediate recall (P for interaction = 0.005). Better performance in these 2 tests was associated with vitamin B-12 in APOE epsilon4 carriers but not in APOE epsilon4 noncarriers. The association between vitamin B-12 and cognitive function was moderated by APOE epsilon4 status.
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Variants of the SLC22A4 gene are associated with susceptibility to rheumatoid arthritis and Crohn's disease. SLC22A4 codes for an integral membrane protein, OCTN1, that has been presumed to carry organic cations like tetraethylammonium across the plasma membrane. Here, we show that the key substrate of this transporter is in fact ergothioneine (ET). Human OCTN1 was expressed in 293 cells. A substrate lead, stachydrine (alias proline betaine), was identified by liquid chromatography MS difference shading, a new substrate search strategy. Analysis of transport efficiency of stachydrine-related solutes, affinity, and Na⁺ dependence indicates that the physiological substrate is ET. Efficiency of transport of ET was as high as 195 μl per min per mg of protein. By contrast, the carnitine transporter OCTN2 from rat did not transport ET at all. Because ET is transported >100 times more efficiently than tetraethylammonium and carnitine, we propose the functional name ETT (ET transporter) instead of OCTN1. ET, all of which is absorbed from food, is an intracellular antioxidant with metal ion affinity. Its particular purpose is unresolved. Cells with expression of ETT accumulate ET to high levels and avidly retain it. By contrast, cells lacking ETT do not accumulate ET, because their plasma membrane is virtually impermeable for this compound. The real-time PCR expression profile of human ETT, with strong expression in CD71⁺ cells, is consistent with a pivotal function of ET in erythrocytes. Moreover, prominent expression of ETT in monocytes and SLC22A4 polymorphism associations suggest a protective role of ET in chronic inflammatory disorders. • erythrocyte • inflammation
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Objective: To examine the association between long-term tea consumption and depressive and anxiety symptoms in community-living elderly. Design: Community based cross-sectional study. Setting: The Diet and Healthy Aging Study (DaHA), a prospective cohort study in Singapore. Participants: 614 elderly aged 60 years and above, who were free of dementia and cognitive impairment. Measurements: Information on tea consumption was obtained through interviewer-administered questionnaire. Long-term tea drinking was defined as regular consumption for at least 15 years. Depressive and anxiety symptoms were measured using the 15-item Geriatric Depression Scale (GDS-15) and the 20-item Geriatric Anxiety Inventory (GAI), respectively. A generalized structural equation model (gSEM) was applied to ascertain the association between long-term tea consumption and depressive and anxiety symptoms. Results: About 59% of the subjects had consumed tea for over 15 years. Long term tea consumption was significantly associated with a reduced odds of having depressive and anxiety symptoms, after adjusting for demographics (i.e., age, gender, education and ethnicity), comorbid conditions (i.e., heart disease, diabetes, stroke, hypertension and hyperlipidaemia) and long-term coffee consumption. Conclusion: There was evidence suggesting that long-term tea consumption was associated with reduced depressive and anxiety symptoms among community-living elderly. This suggests that it is worthwhile to further investigate the role of tea's bioactive compounds in promoting mental health in aging.
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While mushrooms are the highest dietary source for the unique sulfur-containing antioxidant ergothioneine, little is known regarding levels of the major biological antioxidant glutathione. Thus, our objectives were to determine and compare levels of glutathione, as well as ergothioneine, in different species of mushrooms. Glutathione levels varied >20-fold (0.11 to 2.41 mg/g dw) with some varieties having higher levels than reported for other foods. Ergothioneine levels also varied widely (0.15 to 7.27 mg/g dw) and were highly correlated with those of glutathione (r=0.62, P<0.001). Both antioxidants were more concentrated in pileus than stipe tissues in selected mushrooms species. Agaricus bisporus harvested during the third cropping flush contained higher levels of ergothioneine and glutathione compared to the first flush, possibly as a response to increased oxidative stress. This study demonstrated that certain mushroom species are high in glutathione and ergothioneine and should be considered an excellent dietary source of these important antioxidants.
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Background: Both in vivo and in vitro studies have indicated that edible mushrooms may have preventive effects against cognitive impairment. However, few cohort studies have yet examined the relationship between mushroom consumption and incident dementia. Objective: We examined the relationship between mushroom consumption and incident dementia in a population of elderly Japanese subjects. Design: Prospective cohort study. Setting: Ohsaki Cohort 2006 Study. Participants: 13,230 individuals aged ≥65 years living in Ohsaki City, northeastern Japan. Measurements: Daily mushroom consumption, other lifestyle factors, and dementia incidence. Results: The 5.7 years incidence of dementia was 8.7%. In comparison with participants who consumed mushrooms <1 time/wk, the multi-adjusted HRs (95% CI) for incident dementia among those did so 1-2 times/week and ≥3 times/week were 0.95 (0.81, 1.10) and 0.81 (0.69, 0.95), respectively (P-trend <.01). The inverse association persisted after excluding participants whose dementia event occurred in the first 2 years of follow-up and whose baseline cognitive function was lower. The inverse association did not differ statistically in terms of vegetable consumption (P-interaction = .10). Conclusions: This cohort study suggests that frequent mushroom consumption is significantly associated with a lower risk of incident dementia, even after adjustment for possible confounding factors.
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There is an exponential increase in dementia in old age at a global level because of increasing life expectancy. The prevalence of neurodegenerative diseases such as dementia and Alzheimer's disease (AD) will continue to rise steadily, and is expected to reach 42 million cases worldwide in 2020. Despite the advancement of medication, the management of these diseases remains largely ineffective. Therefore, it is vital to explore novel nature-based nutraceuticals to mitigate AD and other age-related neurodegenerative disorders. Mushrooms and their extracts appear to hold many health benefits, including immune-modulating effects. A number of edible mushrooms have been shown to contain rare and exotic compounds that exhibit positive effects on brain cells both in vitro and in vivo. In this review, we summarize the scientific information on edible and culinary mushrooms with regard to their anti dementia/AD active compounds and/or pharmacological test results. The bioactive components in these mushrooms and the underlying mechanism of their activities are discussed. In short, these mushrooms may be regarded as functional foods for the mitigation of neurodegenerative diseases.
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Ergothioneine (ET), a naturally occurring thione, can accumulate in the human body at high concentrations from diet. Following absorption via a specific transporter, OCTN1, ET may accumulate preferentially in tissues predisposed to higher levels of oxidative stress and inflammation. Given its potential cytoprotective effects, we examined how ET levels change with age. We found that whole blood ET levels in elderly individuals decline significantly beyond 60 years of age. Additionally, a subset of these subjects with mild cognitive impairment had significantly lower plasma ET levels compared with age-matched subjects. This decline suggests that deficiency in ET may be a risk factor, predisposing individuals to neurodegenerative diseases.
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Objectives To examine the relationships between tea consumption habits and incident neurocognitive disorders (NCD) and explore potential effect modification by gender and the apolipoprotein E (APOE) genotype. DesignPopulation-based longitudinal study. SettingThe Singapore Longitudinal Aging Study (SLAS). Participants957 community-living Chinese elderly who were cognitively intact at baseline. MeasurementsWe collected tea consumption information at baseline from 2003 to 2005 and ascertained incident cases of neurocognitive disorders (NCD) from 2006 to 2010. Odds ratio (OR) of association were calculated in logistic regression models that adjusted for potential confounders. ResultsA total of 72 incident NCD cases were identified from the cohort. Tea intake was associated with lower risk of incident NCD, independent of other risk factors. Reduced NCD risk was observed for both green tea (OR=0.43) and black/oolong tea (OR=0.53) and appeared to be influenced by the changing of tea consumption habit at follow-up. Using consistent nontea consumers as the reference, only consistent tea consumers had reduced risk of NCD (OR=0.39). Stratified analyses indicated that tea consumption was associated with reduced risk of NCD among females (OR=0.32) and APOE e4 carriers (OR=0.14) but not males and non APOE e4 carriers. Conclusion Regular tea consumption was associated with lower risk of neurocognitive disorders among Chinese elderly. Gender and genetic factors could possibly modulate this association.
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Ergothioneine (ET) is a diet-derived, thiolated derivative of histidine with antioxidant properties, at least in vitro. Although ET is produced only by certain fungi and bacteria, it can be found at high concentrations in certain human and animal tissues and is absorbed through a specific, high affinity transporter (OCTN1). In liver, heart, joint and intestinal injury, elevated ET concentrations have been observed in injured tissues. The physiological role of ET remains unclear. We thus review current literature to generate a specific hypothesis: that the accumulation of ET in vivo is an adaptive mechanism, involving the regulated uptake and concentration of an exogenous natural compound to minimize oxidative damage.
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Decline in brain function during normal aging is partly due to the long-term effects of oxidative stress and inflammation. Several fruits and vegetables have been shown to possess antioxidant and anti-inflammatory properties. The present study investigated the effects of dietary mushroom intervention on mobility and memory in aged Fischer 344 rats. We hypothesized that daily supplementation of mushroom would have beneficial effects on behavioral outcomes in a dose-dependent manner. Rats were randomly assigned to receive a diet containing either 0%, 0.5%, 1%, 2%, or 5% lyophilized white button mushroom (Agaricus bisporus); after 8 weeks on the diet, a battery of behavioral tasks was given to assess balance, coordination, and cognition. Rats on the 2% or 5% mushroom-supplemented diet consumed more food, without gaining weight, than rats in the other diet groups. Rats in the 0.5% and 1% group stayed on a narrow beam longer, indicating an improvement in balance. Only rats on the 0.5% mushroom diet showed improved performance in a working memory version of the Morris water maze. When taken together, the most effective mushroom dose that produced improvements in both balance and working memory was 0.5%, equivalent to about 1.5 ounces of fresh mushrooms for humans. Therefore, the results suggest that the inclusion of mushroom in the daily diet may have beneficial effects on age-related deficits in cognitive and motor function.
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This review summarizes the literature on the prevalence and incidence rates of dementia in Chinese populations, including survey results outside mainland China. We identified 15 prevalence studies and five incidence studies. The studies consistently reported sharply increased prevalence and incidence rates of dementia with increasing age. As estimated, there are at least 6,464,040 dementia patients in mainland China alone and we expect the number to rise in the coming decades. It is clear that dementia will be a new epidemic of the 21st century without major public health policies and preventive measures that target at the disease. We urge more research and hope that we will be able to prevent dementia or at least delay the onset in the near future with evidence-based measures.
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Elevated homocysteine has emerged as a risk factor for cognitive impairment even in healthy elderly persons. Reduced brain volume and white matter hyperintensities also occur in healthy elderly as well, but the interrelationships between these have not been well studied. We report these interrelationships in non demented, relatively healthy, community-dwelling older adults from a single East Asian population. Two hundred twenty-eight right-handed participants age 55 years and above were evaluated. Persons with medical conditions or neurological diseases other than well-controlled diabetes mellitus and hypertension were excluded. Participants underwent quantitative magnetic resonance imaging of the brain using a standardized protocol and neuropsychological evaluation. Plasma homocysteine, folate, vitamin B(12), and markers for cardiovascular risk: blood pressure, body mass index, fasting blood glucose, and lipid profile were measured. Elevated homocysteine was associated with reduced global cerebral volume, larger ventricles, reduced cerebral white matter volume, and lower cognitive performance in several domains. Elevated homocysteine was associated with reduced white matter volume (β = -20.80, t = -2.9, df = 223, p = 0.004) and lower speed of processing (β = -0.38, t = -2.1, df = 223, p = 0.03), even after controlling for age, gender, and education. However, the association between homocysteine and lower speed of processing disappeared after controlling for white matter volume. Elevated homocysteine was not associated with white matter hyperintensity volume or with hippocampal volume. Although homocysteine and folate levels were correlated, their effects on white matter volume were dissociated. In non demented, relatively healthy adults, elevated homocysteine is associated with lower cognitive scores and reduced cerebral white matter volume. These effects can be dissociated from those related to white matter hyperintensities or reduced folate level.
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Introduction: Few studies have examined neuropsychiatric symptoms in community dwelling older adults with mild cognitive impairment (MCI). In the present study, we compared the prevalence of neuropsychiatric symptoms in older adults with normal cognition, MCI, and dementia in a population-based sample.Methods: Subjects were selected from the Singapore Longitudinal Ageing study. Normal cognitive function was defined as Clinical Dementia Rating (CDR) global score=0 and Mini-Mental State Examination (MMSE) total score ≥24. MCI was defined as CDR global score=0.5, and dementia was defined as CDR global score ≥1. Neuropsychiatric Inventory (NPI) was administered on reliable informants for 293 subjects (136 normal, 133 MCI, and 24 dementia).Results: The prevalence of neuropsychiatric symptoms (at lest one symptom) was 5.9% for normal cognition, 12.8% for MCI, and 50% for dementia. The most common neuropsychiatric symptoms in subjects with MCI were depression/dysphoria (6.8%), irritability/lability (3.8%), apathy/indifference (2.3%), and agitation/aggression (2.3%). NPI total score increased with increasing CDR global score (P<0.001). The adjusted mean NPI total score was 0.07 (SEM=0.49) for normal cognition, 0.86 (SEM=0.46) for MCI, and 4.50 (SEM=0.82) for dementia.Discussion: In community dwelling Asian older adults, we found an increasing prevalence of neuropsychiatric symptoms in subjects with normal cognition, MCI and dementia. Further studies with larger samples and strict criteria for MCI in an Asian population should be conducted.
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Ergothioneine (ET) is a sulfur containing amino acid that functions as an antioxidant. Mushrooms are a primary source of ET containing from 0.4 to 2.0mg/g (dry-weight). The bioavailability of ET from mushrooms in humans remains unclear. We evaluated the bioavailability of ET in healthy men (n=10) in a pilot study, using a randomized, cross-over, dose-response, postprandial time-course design, conducted at the General Clinical Research Center at Pennsylvania State University in 2009. ET was administered through a mushroom test meal containing 8 g and 16 g of mushroom powder. Postprandial red blood cell concentrations of ET were measured. Plasma glucose, triglycerides, HDL, LDL and total cholesterol also were monitored. Biomarkers of inflammation and oxidative stress were evaluated using C-reactive protein and ORAC(total). ET was bioavailable after consuming mushrooms and a trend in the postprandial triglyceride response indicated that there was a blunting effect after both the 8 g and 16 g ET doses were compared with the 0 g dose. Despite ET's antioxidant properties, ORAC(total) values decreased after the 8 g and 16 g mushroom meal. Ergothioneine from A. bisporus mushrooms is bioavailable as assessed by red blood cell uptake postprandially, and consumption is associated with an attenuated postprandial TG response.
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Since its discovery, the unique properties of the naturally occurring amino acid, L-ergothioneine (EGT; 2-mercaptohistidine trimethylbetaine), have intrigued researchers for more than a century. This widely distributed thione is only known to be synthesized by non-yeast fungi, mycobacteria and cyanobacteria but accumulates in higher organisms at up to millimolar levels via an organic cation transporter (OCTN1). The physiological role of EGT has yet to be established. Numerous in vitro assays have demonstrated the antioxidant and cytoprotective capabilities of EGT against a wide range of cellular stressors, but an antioxidant role has yet to be fully verified in vivo. Nevertheless the accumulation, tissue distribution and scavenging properties, all highlight the potential for EGT to function as a physiological antioxidant. This article reviews our current state of knowledge. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.
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A double-blind, parallel-group, placebo-controlled trial was performed on 50- to 80-year-old Japanese men and women diagnosed with mild cognitive impairment in order to examine the efficacy of oral administration of Yamabushitake (Hericium erinaceus), an edible mushroom, for improving cognitive impairment, using a cognitive function scale based on the Revised Hasegawa Dementia Scale (HDS-R). After 2 weeks of preliminary examination, 30 subjects were randomized into two 15-person groups, one of which was given Yamabushitake and the other given a placebo. The subjects of the Yamabushitake group took four 250 mg tablets containing 96% of Yamabushitake dry powder three times a day for 16 weeks. After termination of the intake, the subjects were observed for the next 4 weeks. At weeks 8, 12 and 16 of the trial, the Yamabushitake group showed significantly increased scores on the cognitive function scale compared with the placebo group. The Yamabushitake group's scores increased with the duration of intake, but at week 4 after the termination of the 16 weeks intake, the scores decreased significantly. Laboratory tests showed no adverse effect of Yamabushitake. The results obtained in this study suggest that Yamabushitake is effective in improving mild cognitive impairment.
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The superoxide radical (O.2-) and nitric oxide (NO.) combine very rapidly to form peroxynitrite (ONOO-), a reactive tissue damaging nitrogen species thought to be involved in the pathology of several chronic diseases. The natural product ergothioneine protects against the nitration of tyrosine and the inactivation of alpha 1-antiproteinase by ONOO-. Ergothioneine merits further investigation as a biological and therapeutic antioxidant agent.
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The concept of cognitive impairment intervening between normal ageing and very early dementia has been in the literature for many years. Recently, the construct of mild cognitive impairment (MCI) has been proposed to designate an early, but abnormal, state of cognitive impairment. MCI has generated a great deal of research from both clinical and research perspectives. Numerous epidemiological studies have documented the accelerated rate of progression to dementia and Alzheimer's disease (AD) in MCI subjects and certain predictor variables appear valid. However, there has been controversy regarding the precise definition of the concept and its implementation in various clinical settings. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. It is suggested that the diagnosis of MCI can be made in a fashion similar to the clinical diagnoses of dementia and AD. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. By refining the criteria for MCI, clinical trials can be designed with appropriate inclusion and exclusion restrictions to allow for the investigation of therapeutics tailored for specific targets and populations.