phytoestrogens and Dementia

S-equol, a metabolite of soy isoflavone daidzein transformed by the gut microbiome, is the most biologically potent among all soy isoflavones and their metabolites. Soy isoflavones are phytoestrogens and exert their actions through estrogen receptor-β. Epidemiological studies in East Asia, where soy isoflavones are regularly consumed, show that dietary isoflavone intake is inversely associated with cognitive decline and dementia; however, randomized controlled trials of soy isoflavones in Western countries did not generally show their cognitive benefit. The discrepant results may be attributed to S-equol production capability; after consuming soy isoflavones, 40-70% of East Asians produce S-equol, whereas 20-30% of Westerners do. Recent observational and clinical studies in Japan show that S-equol but not soy isoflavones is inversely associated with multiple vascular pathologies, contributing to cognitive impairment and dementia, including arterial stiffness and white matter lesion volume. S-equol has better permeability to the blood-brain barrier than soy isoflavones, although their affinity to estrogen receptor-β is similar. S-equol is also the most potent antioxidant among all known soy isoflavones. Although S-equol is available as a dietary supplement, no long-term trials in humans have examined the effect of S-equol supplementation on arterial stiffness, cerebrovascular disease, cognitive decline, or dementia.

Topics: Antioxidants; Cognitive Dysfunction; Dementia; Equol; Estrogen Receptor beta; Gastrointestinal Microbiome; Humans; Isoflavones; Phytoestrogens; Receptors, Estrogen

Cognitive impairment results from a complex interplay of many factors. The most important independent predictor of cognitive decline is age but other contributing factors include demographic, genetic, socio-economic, and environmental parameters, including nutrition. The number of persons with cognitive decline and dementia will increase in the next decades in parallel with aging of the world population. Effective pharmaceutical treatments for age-related cognitive decline are lacking, emphasizing the importance of prevention strategies. There is extensive evidence supporting a relationship between diet and cognitive functions. Thus, nutritional approaches to prevent or slow cognitive decline could have a remarkable public health impact. Several dietary components and supplements have been examined in relation to their association with the development of cognitive decline. A number of studies have examined the role of dietary patterns on late-life cognition, with accumulating evidence that combinations of foods and nutrients may act synergistically to provide stronger benefit than those conferred by individual dietary components. Higher adherence to the Mediterranean dietary pattern has been associated with decreased cognitive decline and incident AD. Another dietary pattern with neuroprotective actions is the Dietary Approach to Stop Hypertension (DASH). The combination of these two dietary patterns has been associated with slower rates of cognitive decline and significant reduction in incident AD. This review evaluates the evidence for the effects of some dietary components, supplements, and dietary patterns as neuroprotective, with potential to delay cognitive decline and the onset of dementia.

Topics: Antioxidants; Autophagy; Caffeine; Catechin; Central Nervous System Stimulants; Chocolate; Cognitive Dysfunction; Curcumin; Dementia; Diet; Fatty Acids, Omega-3; Garlic; Ginkgo biloba; Healthy Aging; Humans; Inflammation; Magnesium; Oxidative Stress; Phytoestrogens; Phytotherapy; Resveratrol; Tea; Vitamins

Menopause is a critical period during which, without timely interventions, increased risks of cardiovascular and metabolic diseases, osteoporosis, sexual dysfunction and premature cognitive decline will contribute to diminished quality-of-life in women. Hormone therapy (HT) used to be the standard of care for managing vasomotor symptoms and prevention of chronic diseases until publication of the Women's Health Initiative (WHI) in 2002. Concerned about risks highlighted in WHI publications, many symptomatic women promptly ceased HT which resulted in increased vasomotor symptoms, osteoporosis-related-fractures and insomnia. Data from post-hoc WHI analyses and newer clinical trials consistently show reductions in coronary heart disease and mortality when estrogen therapy is initiated soon after menopause, whereas administration in later years and/or in combination with progesterone carries increased risks. However, no validated primary preventive strategies are available for younger postmenopausal women (<60 years), highlighting the need to re-evaluate the use of estrogen alone for which the risk-benefit balance appears positive. In contrast, in older women (>60 years), risks associated with oral HT exceed benefits; however transdermal estrogen may offer a safer alternative and should be further evaluated. Alternative therapies such as phytoestrogens and non-hormonal prescriptions may be beneficial for older women or those who are unsuitable for HT. Long-term head-to-head comparisons of HT with alternative interventions are warranted to confirm their efficacy for chronic disease prevention.

Topics: Aged; Aged, 80 and over; Clinical Trials as Topic; Coronary Disease; Dementia; Estradiol; Estrogen Replacement Therapy; Female; Humans; Menopause; Middle Aged; Phytoestrogens; Postmenopause; Resveratrol; Risk Assessment; Time Factors; Women's Health

Observational studies and treatment trials investigating nutrition and cognitive function, with a focus on folate and soya and dementia, were reviewed. Data suggested that effects of folic acid based interventions may only be shown before cognitive decline is evident and/or if people are folate deficient. In older people in Indonesia, Hawai'i and China, tofu, which can contain high levels of phytoestrogens, was found to increase dementia risk. This association was not mediated by a vegetarian diet, socioeconomic status, formaldehyde, thyroid function, or loss of teeth. On the other hand, human observational and animal treatment studies suggested that tempe, a fermented soya product containing phytoestrogens and folate, reduced dementia risk and improved memory. High oestrogen levels were found to increase dementia risk in older women. However, in women with adequate serum folate, high oestrogen levels did not confer additional dementia risk and may protect ageing neurons. In conclusion, reviews seem to suggest that folic acid interventions are only effective on cognitive outcomes in people who are folate deficient and do not have cognitive impairment. Frequent consumption of tofu may have detrimental effects on memory and increase dementia risk in older East Asian people, while tempe may reduce these risks. Possibly folate in tempe offsets the potential negative effects of oestrogenic compounds on ageing neurons.

Topics: Cognitive Dysfunction; Dementia; Female; Folic Acid; Folic Acid Deficiency; Glycine max; Humans; Male; Phytoestrogens; Plant Proteins, Dietary; Soy Foods

It is predicted that around 20% of the worlds population will be age 60 or above by 2050. Prevalence of cognitive decline and dementia is high in older adults and modifiable dietary factors may be able to reduce risk for these conditions. Phytoestrogens are bioactive plant chemicals found in soy, which have a similarity in structure to natural estradiol (the most abundant circulating estrogen). This structural likeness enables phytoestrogens to interact with estrogen receptors in the brain, potentially affecting cognition. However, findings in this domain are largely inconsistent, with approximately 50% of studies showing positive effects of phytoestrogens on cognition and the other half resulting in null/negative findings. This paper provides an updated review of the relationship between consumption of phytoestrogens and risk for cognitive decline and/or dementia. In particular, possible mediators were identified to explain discrepant findings and for consideration in future research. A case can be made for a link between phytoestrogen consumption, thyroid status and cognition in older age, although current findings in this area are very limited. Evidence suggests that inter-individual variants that can affect phytoestrogen bioavailability (and thus cognitive outcome) include age and ability to breakdown ingested phytoestrogens into their bioactive metabolites. Factors of the study design that must be taken into account are type of soy product, dosage, frequency of dietary intake and type of cognitive test used. Guidelines regarding optimal phytoestrogen dosage and frequency of intake are yet to be determined.

Topics: Aging; Animals; Cognition; Cognitive Dysfunction; Dementia; Diet; Functional Food; Glycine max; Humans; Phytoestrogens; Thyroid Gland

Topics: Aged; Aging; Alcohol Drinking; Antioxidants; Avitaminosis; Blood Glucose; Cognition Disorders; Dementia; Estrogens, Non-Steroidal; Humans; Inflammation; Isoflavones; Phytoestrogens; Plant Preparations; Quality of Life

This methodological paper presents both a scientific rationale and a methodological approach for investigating the effects of resveratrol supplementation on mood and cognitive performance in postmenopausal women. Postmenopausal women have an increased risk of cognitive decline and dementia, which may be at least partly due to loss of beneficial effects of estrogen on the cerebrovasculature. We hypothesise that resveratrol, a phytoestrogen, may counteract this risk by enhancing cerebrovascular function and improving regional blood flow in response to cognitive demands. A clinical trial was designed to test this hypothesis.. Healthy postmenopausal women were recruited to participate in a randomised, double-blind, placebo-controlled (parallel comparison) dietary intervention trial to evaluate the effects of resveratrol supplementation (75 mg twice daily) on cognition, cerebrovascular responsiveness to cognitive tasks and overall well-being. They performed the following tests at baseline and after 14 weeks of supplementation: Rey Auditory Verbal Learning Test, Cambridge Semantic Memory Battery, the Double Span and the Trail Making Task. Cerebrovascular function was assessed simultaneously by monitoring blood flow velocity in the middle cerebral arteries using transcranial Doppler ultrasound.. This trial provides a model approach to demonstrate that, by optimising circulatory function in the brain, resveratrol and other vasoactive nutrients may enhance mood and cognition and ameliorate the risk of developing dementia in postmenopausal women and other at-risk populations.

Topics: Affect; Aged; Aged, 80 and over; Cerebrovascular Circulation; Clinical Protocols; Cognition; Cognition Disorders; Dementia; Dietary Supplements; Double-Blind Method; Female; Health Status; Humans; Mental Health; Middle Aged; Neuropsychological Tests; New South Wales; Phytoestrogens; Postmenopause; Regional Blood Flow; Research Design; Resveratrol; Risk Factors; Stilbenes; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Transcranial

Dementias including Alzheimer disease (AD) are three times higher in menopausal women than in men. Phytoestrogens, a group of plant-derived compounds are known to alleviate menopausal complaints including dementia. Millettia griffoniana Baill is a phytoestrogen-rich plant used to treat menopausal complaints and dementia.. Evaluating the estrogenic and neuroprotective potential of Millettia griffoniana on ovariectomized (OVX) rats.. M. griffoniana ethanolic extract has estrogenic, anticholinesterase and antioxidant activities that could account for its anti-amnesic effects. These findings therefore sheds light on why this plant is commonly used in the therapy of menopausal complaints and dementia.

Topics: Animals; Dementia; Estrone; Ethanol; Female; Humans; Mice; Millettia; Phytoestrogens; Plant Extracts; Rats; Rats, Wistar; Scopolamine Derivatives; Superoxide Dismutase

Cell culture studies suggest that phytoestrogens, abundant in soy products such as tempe and tofu, could protect against cognitive decline. Paradoxically, the Honolulu Asia Aging Study reported an increased risk for cognitive impairment and other dementia markers with high tofu (soybean curd) intake.. A cross-sectional study was carried out in 2 rural sites (Borobudur and Sumedang) and 1 urban site (Jakarta) among mainly Javanese and Sundanese elderly (n = 719, 52-98 years of age). Memory was measured using a word learning test sensitive to dementia and soy consumption was assessed using Food Frequency Questionnaire items.. High tofu consumption was associated with worse memory (beta = -0.18, p < 0.01, 95% CI = -0.34 to -0.06), while high tempe consumption (a fermented whole soybean product) was independently related to better memory (beta = 0.12, p < 0.05, 95% CI = 0.00-0.28), particularly in participants over 68 years of age. Fruit consumption also had an independent positive association. The analyses were controlled for age, sex, education, site and intake of other foods.. The results for tofu consumption as a risk factor for low memory function may tie in with the Honolulu Asia Aging Study data. It is unclear whether these negative associations could be attributed to potential toxins or to its phytoestrogen levels. Estrogen (through which receptors phytoestrogens can exert effects) was found to increase dementia risk in women over 65 years of age. Tempe contains high levels of phytoestrogens, but (due to fermentation) also exhibits high folate levels which may exert protective effects. Future studies should validate these findings and investigate potential mechanisms.

Topics: Aged; Aged, 80 and over; Cross-Sectional Studies; Dementia; Eating; Female; Humans; Indonesia; Linear Models; Male; Memory; Memory Disorders; Middle Aged; Nutrition Assessment; Phytoestrogens; Risk Factors; Sex Distribution; Soy Foods