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Eating soya improves memory
Abstract
Soya foods are rich in isoflavone phytoestrogens with weak agonist activity at oestrogen receptors. Oestrogen treatment has been found to improve memory in men awaiting gender reassignment and in post-menopausal women.
To examine the effects of supervised high versus low soya diets on attention, memory and frontal lobe function in young healthy adults of both sexes.
Student volunteers were randomly allocated to receive, under supervision, a high soya (100 mg total isoflavones/day) or a low soya (0.5 mg total isoflavones/day) diet for 10 weeks. They received a battery of cognitive tests at baseline and then after 10 weeks of diet.
Those receiving the high soya diet showed significant improvements in short-term (immediate recall of prose and 4-s delayed matching to sample of patterns) and long-term memory (picture recall after 20 min) and in mental flexibility (rule shifting and reversal). These improvements were found in males and females. In a letter fluency test and in a test of planning (Stockings of Cambridge), the high soya diet improved performance only in females. There was no effect of diet on tests of attention or in a category generation task. Those on the high soya diet rated themselves as more restrained and, after the tests of memory and attention, they became less tense than did those on the control diet.
Significant cognitive improvements can arise from a relatively brief dietary intervention, and the improvements from a high soya diet are not restricted to women or to verbal tasks.
... As a result, very little is known about the effect of polyphenol interventions on brain-related aging processes in healthy young humans. Additionally, the few available studies in this field demonstrate controversial findings; some of them indicate improved brain function following acute and/or chronic ingestion of polyphenol-rich supplementation [36][37][38][39][40], while other findings fail to prove beneficial effects on cognitive function and brain structures of young and middle-aged adults [41][42][43]. ...
... Sixteen studies [36][37][38][39][40][41][42][43][45][46][47][48][49][50][51][52] examining the effects of (poly)phenol-rich supplementation on cognitive functions and/or brain related parameters were considered to meet the specific inclusion criteria and were included in the current SR. ...
... Seven papers [36,38,[45][46][47][48]50] examined the effect of rich-(poly)phenol supplementation on cognitive function (e.g., reaction time, memory, learning abilities, attention, and executive functioning), as well as a variety of brain-related parameters (e.g., neuroplasticity, cerebral hemodynamics and blood flow). Six studies [37,[39][40][41]49,51] only examined the effect of rich-(poly)phenol supplementation on cognitive function. Three studies [42,43,52] only examined the change in serum BDNF [42,43] and stroke volume (SV) [52] following rich-(poly)phenol supplementation. ...
Context: Affecting older and even some younger adults, neurodegenerative disease represents a global public health concern and has been identified as a research priority. To date, most anti-aging interventions have examined older adults, but little is known about the effects of polyphenol interventions on brain-related aging processes in healthy young and middle-aged adults. Objective: This systematic review and meta-analysis aimed to evaluate the acute and chronic effects of (poly)phenol-rich diet supplementation on cognitive function and brain health in young and middle-aged adults. In July 2019, two electronic databases (PubMed and Web of Science) were used to search for relevant trials examining the effect of acute or chronic (poly)phenol-rich supplementation on cognitive function and neuroprotective measures in young and middle-aged adults (
... [26][27][28][29] Cheng et al 30 conducted a meta-analysis of the effects of ISFs in postmenopausal women, which indicated that ISFs improve cognitive function in this group. However, trials that included men or young women, some of which suggested positive effects of ISFs on cognition, 32,34 were not included in their analysis, 23,[31][32][33][34] In addition, they failed to capture all of the trials involving postmenopausal women, 22,35 and they included a study of red clover, which only contains 2% soy isoflavones. 36 The primary aim of this systematic review and meta-analysis was to determine the effect of ISFs on overall and domain-specific cognitive functions by systematically and quantitatively summarizing the results of RCTs that have explored ISFs in adults (both men and women). ...
... [26][27][28][29] Cheng et al 30 conducted a meta-analysis of the effects of ISFs in postmenopausal women, which indicated that ISFs improve cognitive function in this group. However, trials that included men or young women, some of which suggested positive effects of ISFs on cognition, 32,34 were not included in their analysis, 23,[31][32][33][34] In addition, they failed to capture all of the trials involving postmenopausal women, 22,35 and they included a study of red clover, which only contains 2% soy isoflavones. 36 The primary aim of this systematic review and meta-analysis was to determine the effect of ISFs on overall and domain-specific cognitive functions by systematically and quantitatively summarizing the results of RCTs that have explored ISFs in adults (both men and women). ...
... Regarding blinding, most RCTs used placebos that were similar to the interventions, and only some RCTs 32,33,35,45 reported that they also performed blinding of the outcome assessors. In some RCTs, 20,21,24,34,45,46 the loss-to-follow-up rate differed between the intervention group and control group. The study characteristics are summarized in Table 2 [19][20][21][22][23]25,[31][32][33][34][35][44][45][46][47] . ...
Context:
The results of preclinical and observational studies support the beneficial effect of soy isoflavones on cognition.
Objective:
This review aimed to evaluate the effects of soy isoflavones on cognition in adults.
Data sources:
The PUBMED, EMBASE, Ovid Medline, Cochrane Library, and clinicaltrials.gov databases were searched.
Study selection:
Two researchers independently screened 1955 records, using the PICOS criteria: participants were adults; intervention was dietary sources with soy isoflavones or isolated soy isoflavones; comparator was any comparator; outcome was cognitive function; study type was randomized controlled trials (RCTs). A third researcher was consulted to resolve any discrepancies. Sixteen RCTs were included and their quality assessed.
Data extraction:
Information on study design, characteristics of participants, and outcomes was extracted. PRISMA guidelines were followed.
Data analysis:
A random-effects meta-analysis was used to pool estimates across studies. In the 16 RCTs (1386 participants, mean age = 60 y), soy isoflavones were found to improve overall cognitive function (standardized mean difference [SMD], 0.19; 95% confidence interval [CI], 0.07-0.32) and memory (SMD, 0.15; 95%CI, 0.03-0.26).
Conclusion:
The results showed that soy isoflavones may improve cognitive function in adults.
Systematic review registration:
PROSPERO registration no. CRD42018082070.
... Cognitive performance and clinical ratings were assessed every 4 weeks with a 6-test neuropsychological battery assessing functions shown to have improved measurably in previous isoflavone and estrogen trials. [18][19][20][21][22][23][24][25] An interim analysis was planned after 36 participants had completed 12 weeks to estimate final sample size and to adjust the allocation ratio but was not carried out due to rapid recruitment. ...
... Therefore, we considered trials of various soy isoflavones that showed efficacy on neuropsychological and clinical ratings and with sample sizes ranging from 34 to 389 participants over 6 weeks to 12 months treatment. [18][19][20][21][22][23][24][25][40][41][42][43][44] We planned an interim analysis after 36 participants completed 12 weeks of randomized, blinded, parallel-group treatment. The upper 95% confidence limits of the 8-and 12-week outcomes was to be used to re-estimate the remaining sample sizes. ...
... 58 Further, most studies that observed favorable effects of soy extract products on vasomotor symptoms and cognitive function enrolled more participants per treatment group, and those with fewer participants had longer treatment periods. [18][19][20][21][22][23][24][25][40][41][42][43][44] Moreover, in a level 1 clinical trial of 350 healthy, postmenopausal women, long-term dietary soy isoflavones in a dose comparable to that of traditional Asian diets had no effect on global cognition but may have improved visual memory. 40 Thus, although our trial was planned to determine the initial tolerability and safety of phytoSERM exposure at 2 doses, it was underpowered to determine efficacy on vasomotor and cognition at either dose. ...
Objective:
PhytoSERM is a formulation of genistein, daidzein, and S-equol that has an 83-fold selective affinity for estrogen receptor-β (ERβ); and may enhance neuron function and estrogenic mechanisms in the brain without having peripheral estrogenic activity.
Methods:
We conducted an overarching, two-stage, dose-ranging, double-blinded, randomized, placebo-controlled trial of 12 weeks duration comparing 50 and 100 mg/d of phytoSERM with placebo for noncognitively impaired, perimenopausal women aged 45 to 60, with intact uteri and ovaries, with at least one cognitive complaint, and one vasomotor-related symptom. Primary objectives were to assess safety and tolerability of a 50 and 100 mg daily dose; and, secondly, to evaluate potential indicators of efficacy on cognition and vasomotor symptoms over 4 and 12 weeks, and using an embedded, 4-week, 2-period, placebo-controlled crossover trial for a subset of participants.
Results:
Seventy-one women were randomized to treatment; 70 were evaluated at 4 weeks; 12 were entered into the crossover study; 5 did not complete 12 weeks. Reasons for discontinuation were withdrawal of consent (n = 1) and lost to follow-up (n = 4). Adverse events occurred in 16.7% (n = 4) placebo, 39.1% (n = 9) 50 mg/d, and 29.2% (n = 7) 100 mg/d treated participants; 85% were mild and none was severe. Vaginal bleeding occurred in 0, placebo; 1, 50 mg; and 3, 100 mg/d participants.
Conclusions:
The phytoSERM formulation was well tolerated at 50 and 100 mg daily doses. Based on safety outcomes, vaginal bleeding at the 100 mg dose, and vasomotor symptoms and cognitive outcomes at 12 weeks, a daily dose of 50 mg was considered preferable for a phase 2 efficacy trial.
... Soy isoflavones can exert both agonistic and antagonistic estrogenic effects [105], and have inhibitory effects on tyrosine kinase, topoisomerase and angiogenesis [106]. There are several studies that mentioned that soy isoflavones can improve cognitive function in both humans and rats [107,108] and the SOPHIA study [109] observed the effects of soy isoflavone supplementation (110 mg/day) on cognitive function of postmenopausal women. A good performance was observed in this treatment. ...
... Some researchers have found that soy isoflavones appear to be detrimental to cognitive function in men [112], showing that middle-aged men with high tofu consumption had lower brain weight and greater cognitive decline compared to those who consumed less tofu. However, other studies demonstrated that supplementation with soy isoflavones improves cognitive function in men [108]. The treatment was carried out in young men, and consisted of the consumption of high doses of soy (100 mg of soy isoflavones/day), showing significant improvements in short-and long-term memory, as well as mental flexibility. ...
Glycine max (L) Merrill, better known as soy or soybean, is a legume of asian origin considered an excellent biotype, given the fact that it contains almost everything the human being needs for the diet. Its cultivation worldwide is one of the most important, and soy itself and its derivatives are highly on demand. The health effects of soy derived foods have been investigated for more than 25 years, and some of them remain controversial. On the other hand, we wondered if soy could be used to ameliorate the toxic effects of heavy metals. Therefore, in this chapter we review general characteristics of soy as well as its nutritional potential, and we compiled the newest information about the health effects of soy. In order to test our hypothesis, we developed a model of animals exposed to cadmium, and we gave them a soy based diet, comparing it with a casein-based diet as control. This allowed us to collect information about its effect on the respiratory and nervous system. Among the results of this review, we show that it reduces the cholesterol level and obesity while also having antidiabetic effects. We enumerate the benefits of soy-based diets on the respiratory system, such as protection against lung cancer and radiotherapy, better lung function in asthma patients and protection against cadmium intoxication. In the cardiovascular system it reduces the risk of coronary heart disease, improves blood pressure, glycemic control, and inflammation while it reduces not all but some of the alterations induced by cadmium exposure on the aorta and heart. It apparently promotes neurogenesis, improves cognitive functions, and reduces the oxidative stress and apoptosis induced by cadmium exposure in the cerebellum. Taken all together, this information let us conclude that soy consumption would exhibit numerous benefits for human health, although future studies should try to elucidate the best outcome considering variables such as gender, age, treatment duration and dosage of soy products consumption in the diet.
... Soybean seeds contain quite a lot of isoflavones, especially genistein, daidzein, and glycitein that can act as phytoestrogen. These isoflavones and some of their metabolites have agonist activity or partial agonists against estrogen receptors so they can act as weak non-steroidal estrogens [7], [8]. Isoflavones are also able to improve cognitive function through the protective mechanism of nervous system [9]. ...
... The soybean seeds were very good quality and certified by BALITKABI, Malang. Soy phytonutrients that are reported mainly contribute to memory ability are isoflavones, especially genistein and daidzein, through their role as phytoestrogen [7] and antioxidant [18]; [19]. Good quality of tempeh should be prepared start from the selection of good soybean seeds. ...
Tempeh is an Indonesian traditional food, made from white soybean seeds by fermentation with Rhizopus mold. Soybean seeds content high isoflavone glycosides. Isoflavones can act as phytoestrogen, antioxidant and improves memory. Isoflavone glycosides are poorly absorbed in the human body, but the aglycone isoflavones absorbed quickly. Rhizopus mold hydrolize isoflavone glycosides to be aglycone isoflavones during tempeh production. This research was aimed to know the best room temperature and time of fermentation for making soybean tempeh with high content of isoflavones. After rinsing and boiling, the soybean seeds than fermented with Rhizopus oligosporus. Three conditions were applied: (a) ambient temperature (27-32oC) without air circulation, (b) 27±0.5 oC, and (c) 30±0.5 oC both with air circulations. Inner temperature of tempeh was recorded hourly. Total isoflavones were measured with UV spectrophotometer every 6 hours. Based on this study, fermentation at condition a caused the tempeh too hot and rotted quickly. Fermentation at condition b and c produced tempeh with good quality. Tempeh ripening was reached between 31-32 hours with inner temperature 32-33 oC. Fermentation for 72 hours at condition b was chosen because its high total isoflavones content (0.089% w/w), but decrease about 20% compare to soybean seeds (0.112% w/w).
... Soybean seeds contain quite a lot of isoflavones, especially genistein, daidzein, and glycitein that can act as phytoestrogens. These isoflavones and some of their metabolites have agonist activity or partial agonists against estrogen receptors so they can act as weak non-steroidal estrogens [7], [8]. Isoflavones are also able to improve cognitive function through the protective mechanism of nervous system [9]. ...
... The soybean seeds were very good quality and certified by BALITKABI, Malang. Soy phytonutrients that are reported mainly contribute to memory ability are isoflavones, especially genistein and daidzein, through their role as phytoestrogens [7] and antioxidant [18]; [19]. Good quality of tempeh should be prepared start from the selection of good soybean seeds. ...
Tempeh is an Indonesian traditional food, made from white soybean seeds by fermentation with Rhizopus mold. Soybean seeds content high isoflavone glycosides. Isoflavones can act as phytoestrogen, antioxidant and improves memory. Isoflavone glycosides are poorly absorbed in the human body, but the aglycone isoflavones absorbed quickly. Rhizopus mold hydrolize isoflavone glycosides to be aglycone isoflavones during tempeh production. This research was aimed to know the best room temperature and time of fermentation for making soybean tempeh with high content of isoflavones. After rinsing and boiling, the soybean seeds than fermented with Rhizopus oligosporus. Three conditions were applied: (a) ambient temperature (27-32oC) without air circulation, (b) 27±0.5 oC, and (c) 30±0.5 oC both with air circulations. Inner temperature of tempeh was recorded hourly. Total isoflavones were measured with UV spectrophotometer every 6 hours. Based on this study, fermentation at (a) condition caused the tempeh too hot and rotted quickly. Fermentation at (b) and (c) conditions produced tempeh with good quality. Tempeh ripening was reached between 32-32 hours with inner temperature 32-33oC. Fermentation for 72 hours at condition (b) was chosen because its high total isoflavones content (0.089% w/w), but decrease about 20% compare to soybean seeds (0.112% w/w).
... There is a differential effect of soy isoflavones on the brain of men and women, which suggests customization of soy intake may be a potential targeted therapy. A short-term consumption of a high-soy diet (100 mg/d) was associated with enhancement in both short-and long-term memory and improvement in cognitive functions [109]. Similar findings were reported in the Soy and Postmenopausal Health in Aging (SOPHIA) study of postmenopausal women who consumed 110 mg/d soy isoflavones [110]. ...
Many strides have been made in the field of nutrition that are making it an attractive field not only to nutrition professionals but also to healthcare practitioners. Thanks to the emergence of molecular nutrition, there is a better appreciation of how the diet modulates health at the cellular and molecular levels. More importantly, the advancements in brain imaging have produced a greater appreciation of the impact of diet on brain health. To date, our understanding of the effect of nutrients on brain health goes beyond the action of vitamins and minerals and dives into the intracellular, molecular, and epigenetic effects of nutrients. Bioactive compounds (BCs) in food are gaining a lot of attention due to their ability to modulate gene expression. In addition, bioactive compounds activate some nuclear receptors that are the target of many pharmaceuticals. With the emergence of personalized medicine, gaining an understanding of the biologically active compounds may help with the customization of therapies. This review explores the prominent BCs that can impact cognitive functions and mental health to deliver a potentially prophylactic framework for practitioners. Another purpose is to identify potential gaps in the literature to suggest new research agendas for scientists.
... The main constituents of soybean (Glycine max (L.) Merr., family Leguminosae) are represented by dietary fibers, proteins, soyasaponin glycosides, and isoflavones. Soyasaponin glycosides have been shown to exhibit phytoestrogenic [64], antilipidemic [65], and memory-enhancing effects [66]. Its phytochemicals, isoflavones, and soyasaponins, have been extensively employed in neurodegeneration research for their antioxidant [62], anti-inflammatory [67], and memory-modulation effects [68]. ...
The socioeconomic burden of Alzheimer’s Disease (AD) stems from its characteristic multifactorial etiology and, implicitly, the difficulties associated with its treatment. With the increase in life expectancy and health awareness, nutraceuticals and functional foods are filling in the gaps left by the limitation of classical medical treatment in chronic conditions associated with lifestyle factors, such as neurological disorders. Processes, such as fermentation that enhance food phytochemical content are garnering increased attention due to their functional and health-related properties. This systematic review aims to provide an overview of the evidence of phytochemicals from fermented food sources inducing therapeutic outcomes and cognitive benefits from in vivo experimental models of Alzheimer’s Disease. The present systematic review was conducted in accordance with PRISMA guidelines. Searches were performed in the following databases: MEDLINE, Embase, Cochrane, Scopus, Google Scholar, and Science Citation Index Expanded (Web of Science) by two independent reviewers. Titles and abstracts yielded by the search were screened for eligibility against the inclusion criteria. The search strategy yielded 1899 titles, encompassing studies from 1948 to 2022. After the removal of duplicates, and screening of titles, abstracts, and full texts, thirty three studies obtained from the original search strategy and seven studies from references satisfied the inclusion criteria and were included in the present systematic review. Several studies have emphasized the potential of fermentation to yield small-molecule phytochemicals that are not present in raw products. When these phytochemicals are combined, their collective strength has demonstrated the ability to exceed the antioxidant, anti-inflammatory, and neuroprotective benefits of individual phytochemicals when given in their pure form. Among the various fermented foods that have been studied, soy isoflavones obtained through fermentation have shown the most substantial evidence of altering phytochemical content and improving outcomes in animal models of AD. While promising in initial results, other fermented foods and traditional medicines require more detailed research in order to establish their effectiveness and proper utilization. As is, many of the experimental designs lacked phytochemical analysis of the used fermented product or comparison with the non-fermented counterpart. This, coupled with proper reporting in animal studies, will significantly raise the quality of performed studies as well as the weight of obtained results.
... Beyond treatment of prostate, colon, kidney, pancreatic, ovarian, breast, and lung cancers 38, , therapeutic potential of genistein extends to the treatment of cardiovascular diseases [68][69][70] , postmenopausal 71,72 and gastrointestinal 73 ailments, and bone loss [74][75][76][77] . Genistein has been investigated in 75 clinical trials (clinicaltrials.gov), ...
Calcium-selective oncochannel TRPV6 is the major driver of cell proliferation in human cancers. While significant effort has been invested in the development of synthetic TRPV6 inhibitors, natural channel blockers have been largely neglected. Here we report the structure of human TRPV6 in complex with the plant-derived phytoestrogen genistein, extracted from Styphnolobium japonicum, that was shown to inhibit cell invasion and metastasis in cancer clinical trials. Despite the pharmacological value, the molecular mechanism of TRPV6 inhibition by genistein has remained enigmatic. We use cryo-EM combined with electrophysiology, calcium imaging, mutagenesis, and molecular dynamics simulations to show that genistein binds in the intracellular half of the TRPV6 pore and acts as an ion channel blocker and gating modifier. Genistein binding to the open channel causes pore closure and a two-fold symmetrical conformational rearrangement in the S4–S5 and S6-TRP helix regions. The unprecedented mechanism of TRPV6 inhibition by genistein uncovers new possibilities in structure-based drug design.
... 42 A case-control study suggested that in men, supplementation with soy isoflavone improved cognitive function. 43 According to former reports, there are several estrogen receptors in the central nervous system. These receptors have a significant role in cognition and memory operation. ...
In specific populations, soy products have been a part of their diet for many centuries. Soybeans are known to be beneficial mostly because of being rich sources of isoflavones. Various studies showed that Soy isoflavones such as daidzein and genistein have positive effects on gastrointestinal health, cancer prevention, and health promotion in postmenopausal women. In recent years, many studies focused on the neuroprotective effects of soy isoflavones in animal models and humans. This review includes the latest literature on the effects of soy isoflavones in various neurological disorders. In conclusion, soy isoflavones have neuroprotective, anti-inflammatory, and anti-oxidant effects and can be used to prevent stroke, improve memory and cognitive function, reduction of Parkinson’s disease symptoms, and also as a therapeutic agent in multiple sclerosis.
... Human observational and interventional studies have hinted at the potential benefits of such foods and their regular intake [reviewed in (289)]. The efficacy of isoflavones on cognition and aspects of memory are well reported (67,122,141,145,198,214,255,259), and may relate to their potential to mimic the actions of estrogens in the brain (33,191), or to influence the synthesis of acetylcholine and neurotrophic factors (341,342). With regard to other flavonoids, human data are somewhat scarcer. ...
... It could be speculated that isoflavones are effective in earlier age only because of their possible action as estrogen-related effects. Some studies indeed showed that effects are mainly found several years before menopause (i.e., perimenopause), when the ovaries start to produce less estrogen, or in young postmenopausal women (93,94). However, two studies in perimenopausal women included in this review do not support this claim (41). ...
Life expectancy steadily increases, and so do age-associated diseases, leading to a growing population suffering from cognitive decline and dementia. Impairments in working memory (WM) and episodic memory (EM) are associated with an increased risk of developing dementia. While there are no effective pharmacological therapies to preserve or enhance cognition and to slow down the progression from mild memory complaints to dementia so far, plant-based nutrients including polyphenols have been suggested to exert beneficial effects on brain aging. This review studies whether supplementary polyphenols are effective in preserving or enhancing memory in both non-pathological and pathological aging, and whether there are polyphenol efficiency differences between WM and EM. A systematic literature search was conducted and 66 out of 294 randomized clinical trials with 20 participants or more per group, aged 40 years or older were included. These covered a daily intake of 35–1,600 mg polyphenols, e.g., flavonols, flavonoids, isoflovones, anthocyanins, and/or stilbenes, over the course of 2 weeks to 6.5 years duration. In total, around half of the studies reported a significantly improved performance after polyphenol administration compared to control, while three studies reported a worsening of performance, and the remainder did not observe any effects. According to pooled WM and EM meta-analysis of all memory outcomes reported in 49 studies, overall effect size for WM and EM indicated a significant small positive effect on EM and WM with similar estimates (b ~ 0.24, p < 0.001), with large study heterogeneity and significant Funnel asymmetry tests suggesting a positivity bias. These results remained similar when excluding studies reporting extremely large positive effect sizes from the meta-analyses. While Ginkgo biloba and isoflavones did not show benefits in subgroup meta-analyses, those suggested some effects in extracts containing anthocyanins, other flavonoids and resveratrol, again potentially resulting from publication bias. To conclude, a systematic review and meta-analysis indicate that short- to moderate-term polyphenol interventions might improve WM and EM in middle-to older aged adults, however, publication bias in favor of positive results seems likely, rendering definite conclusions difficult. Future studies with larger, more diverse samples and sensitive monitoring of cardiovascular, metabolic and beginning brain pathologies as well as longer follow-up are needed to better understand the impact of age, (beginning) pathologies, gender, and long-term use on polyphenol action.
... However, these studies provided truly captivating results. A case-control study by File et al. [63] indicated that dietary isoflavone supplementation improved cognitive function in men. Individuals received 100 mg of isoflavones per day for 10 weeks. ...
Alzheimer's disease (AD) is the most common form of dementia with a growing incidence rate primarily among the elderly. It is a neurodegenerative, progressive disorder leading to significant cognitive loss. Despite numerous pieces of research, no cure for halting the disease has been discovered yet. Phytoestrogens are nonestradiol compounds classified as one of the endocrine-disrupting chemicals (EDCs), meaning that they can potentially disrupt hormonal balance and result in developmental and reproductive abnormalities. Importantly, phytoestrogens are structurally, chemically, and functionally akin to estrogens, which undoubtedly has the potential to be detrimental to the organism. What is intriguing, although classified as EDCs, phytoestrogens seem to have a beneficial influence on Alzheimer's disease symptoms and neuropathologies. They have been observed to act as antioxidants, improve visual-spatial memory, lower amyloid-beta production, and increase the growth, survival, and plasticity of brain cells. This review article is aimed at contributing to the collective understanding of the role of phytoestrogens in the prevention and treatment of Alzheimer's disease. Importantly, it underlines the fact that despite being EDCs, phytoestrogens and their use can be beneficial in the prevention of Alzheimer's disease.
... Based on evidence that a number of isoflavones or their metabolites can penetrate the BBB 114, 115 , our findings suggest that the extracts and isoflavones examined in this study have the potential to lower the risk of PD or slow disease progression. Studies in humans revealed that consuming 60 or 100 mg total isoflavone equivalent per day for 10 to 12 weeks resulted in improved cognitive function31,147 , suggesting that isoflavone supplementation is a viable strategy to promote brain health. An important area of future research will be to determine whether isoflavones interact with existing PD medications, leading to adverse effects in patients. ...
Parkinson's disease (PD) is a neurodegenerative disorder characterized by nigrostriatal degeneration and the spreading of aggregated forms of the presynaptic protein α-synuclein (aSyn) throughout the brain. PD patients are currently only treated with symptomatic therapies, and strategies to slow or stop the progressive neurodegeneration underlying the disease's motor and cognitive symptoms are greatly needed. The time between the first neurobiochemical alterations and the initial presentation of symptoms is thought to span several years, and early neuroprotective dietary interventions could delay the disease onset or slow PD progression. In this study, we characterized the neuroprotective effects of isoflavones, a class of dietary polyphenols found in soy products and in the medicinal plant red clover (Trifolium pratense). We found that isoflavone-rich extracts and individual isoflavones rescued the loss of dopaminergic neurons and the shortening of neurites in primary mesencephalic cultures exposed to two PD-related insults, the environmental toxin rotenone and an adenovirus encoding the A53T aSyn mutant. The extracts and individual isoflavones also activated the Nrf2-mediated antioxidant response in astrocytes via a mechanism involving inhibition of the ubiquitin-proteasome system, and they alleviated deficits in mitochondrial respiration. Furthermore, an isoflavone-enriched soy extract reduced motor dysfunction exhibited by rats lesioned with the PD-related neurotoxin 6-OHDA. These findings suggest that plant-derived isoflavones could serve as dietary supplements to delay PD onset in at-risk individuals and mitigate neurodegeneration in the brains of patients.
... The many phytochemicals present in soy include isoflavones, phytic acid, trypsin inhibitors and saponins (Anderson and Wolf, 1995). In particular, the beneficial properties of isoflavones have been the subject of interest (File et al., 2001). ...
This is to inform you that above manuscript is reviewed and appraised by the review committee members of IARA and it is accepted for the purpose of publication in the "Bioscience Biotechnology Research Communications" having ISSN: 0974-6455 that will be available online at http://bbrc.in You have to send following documents at iarajournals@gmail.com before 17 th January, 2021.
... The many phytochemicals present in soy include isoflavones, phytic acid, trypsin inhibitors and saponins (Anderson and Wolf, 1995). In particular, the beneficial properties of isoflavones have been the subject of interest (File et al., 2001). ...
... GEN shows different binding affinity towards ERα and ERβ. Its binding affinity towards ERβ is seven to eight times higher as compared to ERα (File et al., 2001;Tzagarakis-Foster et al., 2001). ERβ is abundantly present in the brain regions associated with learning and memory namely neocortex, hippocampus and nuclei of the basal forebrain (Shughrue et al., 1997;Wang et al., 2001;Xu et al., 2009). ...
Genistein (GEN) is a well known phytoestrogen. It acts through estrogen receptor (ER) and performs plethora of functions in the brain. ERK1/2 is an activated kinase which involves in neuron differentiation, adult neurogenesis and several brain functions including learning and memory. However, GEN dependent expression of ERK1/2 and its effect in learning and memory of mice are unknown. In this study, Swiss albino male mice of 25weeks weighing 30 g were used for the experiments. Mice were placed in two groups- control (C) and genistein treated (GEN). Treated group received GEN dissolved in sesame oil (1 mg/kg/day) whereas the control group received sesame oil only. To study the effects of GEN on learning and memory, open-field (OF) test and novel object recognition (NOR) test were performed. Moreover, immunoblotting (IB) was performed to check the expression of ERK1/2 in the mouse brain of both groups. In the OF test, no significant change was observed in motor activity and anxiety in GEN treated mice as compared to control. Moreover, NOR test suggested that entry towards the dissimilar object was higher in case of GEN treated mice as compared to control. These findings suggest higher learning and memory of GEN treated mice than of control. IB showed that the expression of ERK1/2 was significantly high in GEN treated mouse brain as compared to control. Such study may be helpful to understand GEN mediated learning and memory involving ERK1/2.
... Based on evidence that a number of isoflavones or their metabolites can penetrate the BBB 114, 115 , our findings suggest that the extracts and isoflavones examined in this study have the potential to lower the risk of PD or slow disease progression. Studies in humans revealed that consuming 60 or 100 mg total isoflavone equivalent per day for 10 to 12 weeks resulted in improved cognitive function31,147 , suggesting that isoflavone supplementation is a viable strategy to promote brain health. An important area of future research will be to determine whether isoflavones interact with existing PD medications, leading to adverse effects in patients. ...
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by nigrostriatal degeneration and the spreading of aggregated forms of the presynaptic protein α-synuclein (aSyn) throughout the brain. PD patients are currently only treated with symptomatic therapies, and strategies to slow or stop the progressive neurodegeneration underlying the disease’s motor and cognitive symptoms are greatly needed. The time between the first neurobiochemical alterations and the initial presentation of symptoms is thought to span several years, and early neuroprotective dietary interventions could delay the disease onset or slow PD progression. In this study, we characterized the neuroprotective effects of isoflavones, a class of dietary polyphenols found in soy products and in the medicinal plant red clover ( Trifolium pratense ). We found that isoflavone-rich extracts and individual isoflavones rescued the loss of dopaminergic neurons and the shortening of neurites in primary mesencephalic cultures exposed to two PD-related insults, the environmental toxin rotenone and an adenovirus encoding the A53T aSyn mutant. The extracts and individual isoflavones also activated the Nrf2-mediated antioxidant response in astrocytes via a mechanism involving inhibition of the ubiquitin-proteasome system, and they alleviated deficits in mitochondrial respiration. Furthermore, an isoflavone-enriched soy extract reduced motor dysfunction exhibited by rats lesioned with the PD-related neurotoxin 6-OHDA. These findings suggest that plant-derived isoflavones could serve as dietary supplements to delay PD onset in at-risk individuals and mitigate neurodegeneration in the brains of patients.
Graphical Abstract
The isoflavone-rich extracts red clover and soy and the individual isoflavones daidzein and equol protect neuronal cultures against environmental and genetic triggers of Parkinson’s disease, and rescue motor deficits in rats exposed to the neurotoxin 6-OHDA.
... Isoflavones are known to have several biological effects, including the enhancement of cognitive function [54,55]. Therefore, even small amounts of isoflavones in the diet could still have a positive effect on cognitive functions. ...
Dementia is a pathological condition characterized by a decline inmemory, as well as in other cognitive and social functions. The cellular and molecular mechanisms of brain damage in dementia are not completely understood; however, neuroinflammation is
involved. Evidence suggests that chronic inflammation may impair cognitive performance and that dietary protein source may differentially influence this process. Dietary protein source has previously been shown to modify systemic inflammation in mouse models. Thus, we aimed to investigate the effect of chronic dietary protein source substitution in an ageing and dementia male mouse model, the senescence-accelerated mouse-prone 8 (SAMP8) model. We observed that dietary protein source differentially modified memory as shown by inhibitory avoidance testing at 4 months of age. Also, dietary protein source
differentially modified neuroinflammation and gliosis in male SAMP8 mice. Our results suggest that chronic dietary protein source substitution may influence brain ageing and memory-related mechanisms in male SAMP8 mice. Moreover, the choice of dietary protein source in mouse diets for experimental purposes may need to be carefully considered when interpreting results.
... Considering the increased effectiveness of (poly)phenols in counteracting age-related oxidative stress, recent human studies have examined the role of natural (poly)phenols-rich products in the prevention of cognitive decline and maintenance of brain function [15,16]. Several studies have shown that the consumption of (poly)phenols-rich supplementation can benefit cognitive decline in older adults [19][20][21], as well as in young-and middle-aged populations [22][23][24]. Additionally, polyphenols bind to nuclear estrogen receptor α (ERα) and β (ERβ), thus inducing neuroprotective effects. ...
Background:
Recent anti-aging interventions have shown contradictory impacts of (poly)phenols regarding the prevention of cognitive decline and maintenance of brain function. These discrepancies have been linked to between-study differences in supplementation protocols. This subgroup analysis and meta-regression aimed to (i) examine differential effects of moderator variables related to participant characteristics and supplementation protocols and (ii) identify practical recommendations to design effective (poly)phenol supplementation protocols for future anti-aging interventions.
Methods:
Multiple electronic databases (Web of Science; PubMed) searched for relevant intervention published from inception to July 2019. Using the PICOS criteria, a total of 4303 records were screened. Only high-quality studies (n = 15) were included in the final analyses. Random-effects meta-analysis was used, and we calculated standard differences in means (SDM), effect size (ES), and 95% confidence intervals (CI) for two sufficiently comparable items (i.e., psychomotor function and brain-derived neurotrophic factor (BDNF)). When significant heterogeneity was computed (I2 > 50%), a subgroup and meta-regression analysis were performed to examine the moderation effects of participant characteristics and supplementation protocols.
Results:
The reviewed studies support the beneficial effect of (poly)phenols-rich supplementation on psychomotor functions (ES = -0.677, p = 0.001) and brain plasticity (ES = 1.168, p = 0.028). Subgroup analysis revealed higher beneficial impacts of (poly)phenols (i) in younger populations compared to older (SDM = -0.89 vs. -0.47 for psychomotor performance, and 2.41 vs. 0.07 for BDNF, respectively), (ii) following an acute compared to chronic supplementation (SDM = -1.02 vs. -0.43 for psychomotor performance), and (iii) using a phenolic compound with medium compared to low bioavailability rates (SDM = -0.76 vs. -0.68 for psychomotor performance and 3.57 vs. 0.07 for DBNF, respectively). Meta-regressions revealed greater improvement in BDNF levels with lower percentages of female participants (Q = 40.15, df = 6, p < 0.001) and a skewed scatter plot toward a greater impact using higher (poly)phenols doses.
Conclusion:
This review suggests that age group, gender, the used phenolic compounds, their human bioavailability rate, and the supplementation dose as the primary moderator variables relating to the beneficial effects of (poly)phenol consumption on cognitive and brain function in humans. Therefore, it seems more advantageous to start anti-aging (poly)phenol interventions in adults earlier in life using medium (≈500 mg) to high doses (≈1000 mg) of phenolic compounds, with at least medium bioavailability rate (≥9%).
... Flavonoid-rich food items have enormous biological effects on memory [104,243,244]. The isoflavones derived from soy as well as soy-derived foods are effective in learning and perception via mimicking the estrogen activity in the brain [245]. Furthermore, isoflavones also control the concentrations of ACh as well as various neurotrophic factors such as the nerve growth factor and the BDNF in the frontal cortex, as well as the hippocampus of the brain involved in cognitive function [246,247]. ...
Alzheimer’s disease (AD) is one of the utmost chronic neurodegenerative disorders, which is characterized from a neuropathological point of view by the aggregates of amyloid beta (Aβ) peptides that are deposited as senile plaques and tau proteins which form neurofibrillary tangles (NFTs). Even though advancement has been observed in order to understand AD pathogenesis, currently available therapeutic methods can only deliver modest symptomatic relief. Interestingly, naturally occurring dietary flavonoids have gained substantial attention due to their antioxidative, anti-inflammatory, and anti-amyloidogenic properties as alternative candidates for AD therapy. Experimental proof provides support to the idea that some flavonoids might protect AD by interfering with the production and aggregation of Aβ peptides and/or decreasing the aggregation of tau. Flavonoids have the ability to promote clearance of Aβ peptides and inhibit tau phosphorylation by the mTOR/autophagy signaling pathway. Moreover, due to their cholinesterase inhibitory potential, flavonoids can represent promising symptomatic anti-Alzheimer agents. Several processes have been suggested for the aptitude of flavonoids to slow down the advancement or to avert the onset of Alzheimer’s pathogenesis. To enhance cognitive performance and to prevent the onset and progress of AD, the interaction of flavonoids with various signaling pathways is proposed to exert their therapeutic potential. Therefore, this review elaborates on the probable therapeutic approaches of flavonoids aimed at averting or slowing the progression of the AD pathogenesis.
... En la actualidad, es difícil entender el efecto de los polifenoles en el estado cognitivo, debido a que los estudios publicados son muy diferentes en cuanto a la dosis, test utilizados para medir la cognición y el tipo de poblaciones estudiadas. Estudios sobre los mecanismos biológicos asociados al consumo de polifenoles sugieren que mejoran la capacidad antioxidante, antitrombótica y antiinflamatoria, que previenen la disfunción endotelial mediada por NO y el deterioro de las placas de ateroma evitando el déficit cognitivo (32) y que, además, pueden actuar de manera semejante a los estrógenos, que podrían mejorar la función cognitiva (33). ...
... For example, Long term soy-isoflavonebased supplement (110 mg/d) for 6 months showed better verbal memory than the placebo control group [21]. Similarly, in women aged 50-65 found that intake of 60 mg/d for 3 months resulted in cognitive improvement in several categories related to frontal cortical functions [22]. Another study, involving younger postmenopausal women receiving 160 mg/d isoflavones for 6 months, and results showed an improvement cognitive flexibility [23]. ...
... For example, Long term soy-isoflavonebased supplement (110 mg/d) for 6 months showed better verbal memory than the placebo control group [21]. Similarly, in women aged 50-65 found that intake of 60 mg/d for 3 months resulted in cognitive improvement in several categories related to frontal cortical functions [22]. Another study, involving younger postmenopausal women receiving 160 mg/d isoflavones for 6 months, and results showed an improvement cognitive flexibility [23]. ...
Flavonoids are potential group of phytochemicals found in normal diets
capable of mediating improvements in cognition and may reverse age-related
declines in memory. Aging is associated with alteration of hippocampal synaptic
plasticity and contribute to decline in cognitive functions. The current studies are
directed at a greater understanding of how and why the brain modifies synaptic
strength with dietary-derived phytochemicals (flavonoids) and age-related
declines in cognitive functions (such as learning and memory). Flavonoids
modulate neuronal function and thereby influence cognition. In addition, it has
been suggested that flavonoids may delay the development of Alzheimer’s diseaselike pathology, anxiety, and depression disorders, suggesting a novel therapeutic
strategy. Emerging evidence suggest that flavonoids are modulators of signaling
pathways critical for controlling synaptic plasticity in the brain. For example,
phosphatidylinositol-3 kinase (PI3K)/Akt, mitogen-activated protein kinase,
protein kinase C, pathways could be involved Ca2+ signaling. Significants questions such as: (i) How does flavonoids affect plasticity? (ii) What receptors are
modulating by flavonoids and how are they regulated? (iii) Do flavonoids have a
neuroprotective effect in aging? are asked.
... It has been reported to have protective role in postmenopausal breast cancer with HER2 mutation (Wada et al. 2013, Boucher et al. 2013, Zhang et al. 2012. Other than cancer it has other health benefits in osteoporosis (File et al. 2001, Bone et al. 2000, Wei et al. 2012, coronary heart disease (Tikkanen and Adlercreutz 2000, Beavers et al. 2012, Yamakoshi et al. 2000, Chan et al. 2008, diabetes (Gilbert and Liu 2013, Behloul and Wu 2013, Valsecchi et al. 2011) and cognitive effects (Celec et al. 2005, Kritz-Silverstein et al. 2003. Daidzein has been reported to have antitumor role in prostate cancer (Sugiyama et al. 2013) and in treatment of heart diseases (Tikkanen and Adlercreutz 2000). ...
... In a study by File et al. (2001) reported that long-term and short-term memory could be considerably improved via the consumption of a high dietary soy diet (100 mg total isoflavones/day) in healthy young adults of both sexes for 10 weeks. Nonetheless, clinical studies regarding the therapeutic potential of genistein for AD treatment are still missing. ...
Alzheimer’s disease (AD) is a progressive, irreversible brain disorder characterized by pathological aggregation of the amyloid-β peptide (Aβ) and tau protein; both of these are toxic to neurons. Currently, natural products are regarded as an alternative approach to discover novel multipotent drugs against AD. Dietary soy isoflavone genistein is one of the examples of such agents that occurs naturally and is known to exert a number of beneficial health effects. It has been observed that genistein has the capacity to improve the impairments triggered by Aβ and also it possesses the antioxidant potential to scavenge the AD-mediated generation of free radicals. Furthermore, genistein can interact directly with the targeted signaling proteins and also can stabilize their activity to combat AD. In order to advance the development of AD treatment, a better comprehension of the direct interactions of target proteins and genistein might prove beneficial. Therefore, this article focuses on the therapeutic effects and molecular targets of genistein, which has been found to target directly the Aβ and tau to control the intracellular signaling pathways responsible for neurons death in the AD brain.
... Although a double-blind placebo-controlled trial is the gold standard, there was a vast age difference in the sample (30-80-year age range), and the sample size only consisted of 34 participants. Two other studies with results that differ from our findings included young adults who were given soy supplementation that improved executive function, as well as spatial cognitive performance [73,74]. Both studies had a very small sample size, especially the study by Celec and colleagues [73] with a sample of only 7 participants. ...
Sex hormone changes in adults are known to play a part in aging, including cognitive aging. Dietary intake of phytoestrogens can mimic estrogenic effects on brain function. Since sex hormones differ between genders, it is important to examine gender differences in the phytoestrogen–cognition association. Therefore, the goal of this study is to examine the relationship between urinary phytoestrogens and speed of processing (SOP) and the variation of the association between genders in older adults. Participants were drawn from the 1999–2002 National Health and Nutrition Examination Survey and included 354 individuals aged 65–85 years old. General linear models (GLMs) were used to test for significant gender differences in the relationship between phytoestrogens and SOP. Results from the GLMs showed significant gender differences in the relationship between genistein and SOP. Higher levels of genistein were associated with better SOP in women. This relationship was reversed in men: higher genistein levels were associated with worse performance. Results indicate that there are distinct gender differences in the relationship between genistein and SOP. These results emphasize the importance of considering gender differences when devising dietary and pharmacologic interventions that target phytoestrogens to improve brain health.
... Several studies highlight the beneficial effects of flavonoid-rich foodstuffs' consumption on cognition (Commenges et al., 2000;Letenneur et al., 2007;Spencer, 2010a). Isoflavones from soy and soy-derived foods have been reported to improve learning and memory possibly by their potential to mimic the activity of estrogens in brain (File et al., 2001). These isoflavones also modulate the neuronal concentrations of ACh and neurotrophic factors including the brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus and frontal cortex regions of brain (Pan et al., 1999a,b). ...
Modern research revealed that dietary consumption of flavonoids and flavonoids-rich foods significantly improves cognitive capabilities, inhibits or delays the senescence process and related neurological disorders including Alzheimer's disease (AD). The flavonoids rich foods such as green tea, cocoa, blue berry and other foods appear to improve states of cognitive hypofunction, AD and dementia-like pathological symptoms in different animal models. The mechanism of flavonoids are principally mediated via inhibition of cholinesterases (AChE, BChE), beta secretase (BACE1), free radicals and modulation of signaling pathways implicated in cognitive and neuroprotective performance. Flavonoids interact with several signaling protein pathways like ERK and PI3-kinase/Akt and modulate their actions, leading to their neuroprotective effects. Moreover, they enhance vascular blood flow and instigate neurogenesis particularly in the hippocampus area of the brain in animal models investigated so for. Flavonoids also hamper the progression of pathological symptoms of neuro-degenerative disorders via inhibition of neuronal apoptosis induced byneurotoxic substances including free radicals and beta amyloid proteins (Aβ). All these functions contribute to the maintenance of number, quality of neurons and their synaptic connectivity in the brain. Thus flavonoids can thwart the progression of age related disorders and can be a potential source for the development of new drugs effective in cognitive disabilities disorders.
... (Table 4). In a study with young healthy adults of both sexes, a high soya or a low soya diet for 10 weeks had a beneficial effect and showed significant improvements in short-term and long-term memory as well as in mental flexibility [159]. In another cross-over design study, the administration of 4 capsules/day containing soya isoflavones during 6 weeks improved the spatial working memory of men aged 30-80 years [160]. ...
Alzheimer’s disease (AD) is the most common form of dementia affecting people mainly in their sixth decade of life and at a higher age. It is an extensively studied neurodegenerative disorder yet incurable to date. While its main postmortem brain hallmarks are the presence of amyloid- β plaques and hyperphosphorylated tau tangles, the onset of the disease seems to be largely correlated to mitochondrial dysfunction, an early event in the disease pathogenesis. AD is characterized by flawed energy metabolism in the brain and excessive oxidative stress, processes that involve less adenosine triphosphate (ATP) and more reactive oxygen species (ROS) production respectively. Mitochondria are at the center of both these processes as they are responsible for energy and ROS generation through mainly oxidative phosphorylation. Standardized Ginkgo biloba extract (GBE), resveratrol, and phytoestrogens as well as the neurosteroid allopregnanolone have shown not only some mitochondria-modulating properties but also significant antioxidant potential in in vitro and in vivo studies. According to our review of the literature, GBE, resveratrol, allopregnanolone, and phytoestrogens showed promising effects on mitochondria in a descending evidence order and, notably, this order pattern is in line with the existing clinical evidence level for each entity. In this review, the effects of these four entities are discussed with special focus on their mitochondria-modulating effects and their mitochondria-improving and antioxidant properties across the spectrum of cognitive decline-related disorders. Evidence from preclinical and clinical studies on their mechanisms of action are summarized and highlighted.
... Soy isoflavones, or flavonoids from soybean, namely phytoestrogens, can affect estrogen-mediated processes (Molteni et al. 1995). High soybean diets clearly improve short-term and long-term memory (File et al. 2001). The protective effect of genistein, the most active component of soy isoflavones, against Aβ-induced neurological damage has been reported. ...
We established a model of Alzheimer’s disease in vitro by exposing primary hippocampal neurons of neonatal Wistar rats to the β-Amyloid peptide fragment 25–35, Aβ25–35. We then observed the effects of genistein, a type of soybean isoflavone, on Aβ25–35-incubated hippocampal neuron viability, and the electrophysiological properties of voltage-gated sodium channels (NaV) and potassium channels (KV) in the hippocampal neurons. Aβ25–35 exposure reduced the viability of hippocampal neurons, decreased the peak amplitude of voltage-activated sodium channel currents (INa), and significantly reduced INa at different membrane potentials. Moreover, Aβ25–35 shifted the activation curve toward depolarization, shifted the inactivation curve toward hyperpolarization, and increased the time constant of recovery from inactivation. Aβ25–35 exposure significantly shifted the inactivation curve of transient outward K⁺ currents (IA) toward hyperpolarization and increased its time constant of recovery from inactivation. In addition, Aβ25–35 significantly decreased the peak density of outward-delayed rectifier potassium channel currents (IDR) and significantly reduced IDR value at different membrane potentials. We found that genistein partially reversed the decrease in hippocampal neuron viability, and the alterations in electrophysiological properties of NaV and KV induced by Aβ25–35. Our results suggest that genistein could inhibit Aβ25–35-induced neuronal damage with changes in the electrophysiological properties of NaV and KV.
... The effect size was determined using previous studies assessing cognitive function in healthy men and women (26,27) using a power of 0.90 and α of .05 and allowing for one covariate. To be able to detect a similar difference between the three levels of vitamin D 3 intake for spatial and pattern recognition and memory, a sample size of 8 per group was calculated. ...
Vitamin D may affect cognitive performance, but previous studies are either short term or observational. We conducted a randomized controlled trial of vitamin D supplementation on domain-specific cognitive measures in postmenopausal women. Overweight/obese women with serum 25-hydroxyvitamin D (25OHD) levels less than 30 ng/mL were recruited. Vitamin D3 supplementation (600, 2,000, or 4,000 IU/d) was randomly assigned in a double-blinded manner for 1 year. Serum 25-hydroxyvitamin D, osteocalcin (total and undercarboxylated), amyloid beta, parathyroid hormone, and estradiol were analyzed before and after supplementation. Cognitive tests were administered after treatment. The women (58 ± 6 years; body mass index, 30.0 ± 3.5 kg/m²) had a baseline serum 25-hydroxyvitamin D level of 22.6 ± 5.8 ng/mL that increased to 30.2 ± 5.6, 36.0 ± 4.9, and 40.8 ± 7.0 ng/mL in the 600, 2,000, and 4,000 IU/d groups, respectively (p < .001). Participants taking 2,000 IU/d compared to other doses performed better in learning and memory tests (p < .05), yet the 4,000 IU/d group had a slower reaction time compared to the 600 IU/d group. Multiple regression indicated that serum undercarboxylated osteocalcin predicted tasks associated with reaction time and executive function, whereas body mass index and parathyroid hormone negatively predicted reaction time and executive function (p ≤ .01). These data suggest that vitamin D has differential effects on domain-specific cognitive measures and that a higher dose may negatively affect reaction time.
TRPV6, a representative of the vanilloid subfamily of TRP channels, serves as the principal calcium uptake channel in the gut. Dysregulation of TRPV6 results in disturbed calcium homeostasis leading to a variety of human diseases, including many forms of cancer. Inhibitors of this oncochannel are therefore particularly needed. In this review, we provide an overview of recent advances in structural pharmacology that uncovered the molecular mechanisms of TRPV6 inhibition by a variety of small molecules, including synthetic and natural, plant-derived compounds as well as some prospective and clinically approved drugs.
Obesity, heart disease, diabetes, and cancer are just a few chronic diseases for which proper nutrition has been demonstrated to be a crucial factor in preven-tion. Flavonoids, found in many fruits and vegetables, are a type of dietary polyphenol with potent antioxidant activity and anti-carcinogenic characteris-tics. Flavonoids and foods rich in flavonoids have been shown in recent years to have profound effects on cognitive function, aging, and neurodegenerative diseases like Alzheimer's. Foods high in flavonoids, such as green tea, choco-late, blueberries, and other fruits and vegetables, have ameliorated symptoms of cognitive impairment, Alzheimer's disease, and dementia in several animal models. As a result of their ability to prevent neuronal death generated by neu-rotoxic chemicals such as free radicals and β-amyloid proteins. Furthermore, flavonoids are also effective in slowing the evolution of clinical signs of neuro-degenerative illnesses. In addition, flavonoids can improve lipid profiles by preventing the oxidation of low-density lipoproteins, and these antioxidant ca-pabilities are responsible for their therapeutic impacts. Finally, the potential of flavonoids to induce vasodilation and control apoptotic processes in the endo-thelium is another way in which they benefit the cardiovascular system. This review aims to offer up-to-date information on categorizing these compounds, their primary methods of action in the human body, and their positive impacts on the management of neurodegenerative diseases, cardiovascular disorders, and other life-threatening diseases.
Flavonoids are large group of plant-derived aromatic compounds which have diverse functional capabilities. These polyphenolic compounds promote human immune system and protect body against several health ailments. A lot is needed to explore in terms of their bioavailability and their metabolism so as to utilize their broad range potential. Flavonoids are potent substances which are widely used at present because of their antioxidative, anti-inflammatory, antiviral/bacterial, cardioprotective, antidiabetic, antiaging, and anticarcinogenic properties and still have more to be explored and used in the future. This chapter provides view of current and futuristic application of flavonoids.
Objective: To determine the best temperature and time of fermentation for making soybean (Glycine max (L.) Merril) tempeh seeds with high content of isoflavones. Methods: Five varieties of soybean seeds, Devon-1, Dena-1, Dega-1, Anjasmoro, and Argomulyo, were determined for their isoflavones content using an Ultraviolet (UV) spectrophotometer. A variety containing the highest isoflavones was washed, boiled, peeled, then mixed with tempeh starter (Rhizopus oligosporus culture) at 1 g/kg. The mixture was then poured into plastic bags and flattened with two centimeters of thickness. Fermentation in three conditions: (a) ambient temperature (27-32 °C) without air circulation, (b) 27±0.5 °C, and (c) 30±0.5 °C both with air circulation. The inner temperature, ripening time, and rotting time was recorded. The total isoflavones content was measured every 6 h. Results: The variety of Devon-1 has the highest content of isoflavones (0.112% w/w). Fermentation in condition (a) caused the tempeh too hot(42 °C) and rotted at the 42nd h. Condition (b) produced the best tempeh, ripening at the inner peak temperature (32.5 °C) at the 32nd h; and rotted after the 100th h. Condition (c) produced good tempeh; the ripening occurred at the 31st h at 33 °C and rotted after the 113th h. Tempeh that was produced with condition (b) at the 72nd h has the highest content of isoflavones (0.089% w/w). Conclusion: Fermentation at 27±0.5 °C with air circulation for 72 h produced tempeh with the highest isoflavones content (0.089% w/w), but decrease about 20% compared to its content in seeds (0.112% w/w).
To investigate the mechanism underlying the neurodegeneration of postmenopausal women, the effect of genistein on hippocampal neurodegeneration was investigated in ovariectomized (OVX) Sprague-Dawley rats. Three-month-old female Sprague-Dawley rats were randomly divided into four groups: sham operated; OVX only; genistein-treated OVX (OVX-genistein); and estradiol benzoate-treated OVX (OVX-EB). Genistein and EB were subcutaneously injected into rats of the OVX-genistein and OVX-EB groups, respectively, once a day from the second day after surgery. Behavioral testing began on day 31 after surgery and lasted 5 d. The activities of superoxide dismutase and content of malondialdehyde in serum, the concentration of intrasynaptosome-free calcium, membrane relative viscosity of cerebral synaptosomes, and mean optical density (MOD) of the hippocampal synaptophysin immunoreactivity product were measured, respectively, in the eighth week after surgery. It was found that the escape latency in the OVX-EB and the OVX-genistein groups was significantly lower than that in the OVX control group (p<0.05), whereas in the behavioral test, the platform-passing number was higher than in the OVX control group (p<0.05). [Ca2+]
i
in the cerebral cortical and hippocampal synaptosome of the OVX-only group was remarkably higher than that in the other three groups (p<0.01). The hippocampal synaptosome membrane viscosity of the OVX-only group was significantly higher than that in the sham-operated, OVX-EB (p<0.05) and the OVX-genistein (p<0.01) groups. The MOD of synaptophysin immunoreactive product in the radiation layers of CA1, CA2, CA3 and the molecular layer of the dentate gyrus of the OVX-only group was significantly lower than in the sham-operated, OVX-genistein, and OVX-EB groups (p<0.01). These results suggested that genistein, which has antioxidant properties similar to estradiol, could be used as a substitute for estradiol to prevent or treat central neurodegeneration in postmenopausal women.
Soy is a hotly debated and widely discussed topic in the field of nutrition. However, health practitioners may be ill-equipped to counsel clients and patients about the use of soyfoods because of the enormous, and often contradictory, amount of research that has been published over the past 30 years. As interest in plant-based diets increases, there will be increased pressure for practitioners to gain a working knowledge of this area. The purpose of this review is to provide concise literature summaries (400–500 words) along with a short perspective on the current state of knowledge of a wide range of topics related to soy, from the cholesterol-lowering effects of soy protein to the impact of isoflavones on breast cancer risk. In addition to the literature summaries, general background information on soyfoods, soy protein, and isoflavones is provided. This analysis can serve as a tool for health professionals to be used when discussing soyfoods with their clients and patients.
Due to progressive population aging, a new dementia case occurs at every 3 seconds, placing a heavy burden of disease. Identifying potential risk or preventive factors is emphasized owing to a lack of effective treatment for dementia. There has been emerging evidence on the link of certain dietary components, particularly polyphenols, to brain wellness and cognitive outcomes. Findings from animal and in vitro studies appear more consistent and conclusive. However, such an association has not been investigated in depth in human beings. In this review, we examined studies on the effect of dietary polyphenols (including flavonoids, curcumin, and resveratrol) on cognitive function. Intervention in early stages of dementia/Alzheimer’s disease might be a target to slow down age-related cognitive decline before disease onset. We summarized 28 epidemiological studies (8 cross-sectional and 20 cohort studies) and 55 trials in this review. Preliminary evidence from epidemiological data provides the necessity for intervention trials, even though the measures of polyphenol intake tend to be less precise. Clinical trials are in favor of the role of some polyphenols in benefiting specific domains of cognition. This review also describes the divergence of results and current limitations of research in this field.
Atrazine (ATR) is a widely used herbicide that can induce the degeneration of dopaminergic (DAergic) neurons in the substantia nigra, resulting in a Parkinson’s disease-like syndrome. Despite the high risk of environmental exposure, few studies have investigated strategies for the prevention of ATR neurotoxicity. Our previous studies demonstrated that ATR can impair mitochondrial function, leading to metabolic failure. Cells maintain mitochondrial quality through selective autophagic elimination, termed mitophagy. Soybean isoflavones (SI) possess multiple beneficial bioactivities, including preservation of mitochondria function, so it was hypothesized that SI can protect neurons against ATR toxicity by promoting mitophagy. Pretreatment of SH-SY5Y neurons with SI prevented ATR-induced metabolic failure and cytotoxicity as assessed by intracellular ATP, Na⁺-K⁺-ATPase activity, mitochondrial membrane potential, and cell viability assays. The neuroprotective efficacy of SI was superior to the major individual components genistein, daidzein, and glycitein. Ultrastructural analyses revealed that ATR induced mitochondrial damage, while SI promoted the sequestration of damaged mitochondria into autophagic vesicles. Soybean isoflavones also induced mitophagy as evidenced by upregulated expression of BNIP3/NIX, BEX2, and LC3-II, while co-treatment with the mitophagy inhibitor Mdivi-1 blocked SI-mediated neuroprotection and prevented SI from reversing ATR-induced BEX2 downregulation. Furthermore, BEX2 knockdown inhibited SI-induced activation of the BNIP3/NIX pathway, mitophagy, and neuroprotection. These findings suggest that SI protects against ATR-induced mitochondrial dysfunction and neurotoxicity by activating the BEX2/BNIP3/NIX pathway.
Tempeh sausage is the one of variative and interesting processed provide added value and extend the shelf life of tempeh. The purpose of the research is to determine the quality of tempeh sausages, especially chemical and sensory content produced from various soybean varieties and variation of cooking methods. The research had a Complete Random Design of the factorial pattern with 3 repeats. The first factor is tempeh from various of soybean varieties (Import, Anjasmoro, Argomulyo, Burangrang, and Grobogan), the second factor is the cooking method (steamed, boiled and oven). The observation parameters include: moisture content, ash content, fat level, protein level, and sensory/organoleptic test. The result was showed that varieties of treatment and cooking methods gave a real interaction effect on ash content, fat content and protein of tempeh sausage. Tempeh sausage was produced from imported soybean, has the lowest water content for the oven cooking method and sausage tempeh of soybean Anjasmoro with steamed method has the lowest ash content. Tempeh sausage produced from soybean Argomulyo has the highest fat content for steamed cooking methods and the highest protein for the oven cooking method. Based on sensory analysis, it is known that having the highest level of preference is tempeh sausage from Grobogan and steamed treatment with a moisture content of 56.25%, ash content is 0.97%, fat 17.38%, and protein 12.91%.
Purpose
To explore genistein, the most active component of soy isoflavones, on viability, expression of estrogen receptor (ER) subtypes, choline acetyltransferase (ChAT), and glutamate receptor subunits in amyloid peptide 25-35-induced hippocampal neurons, providing valuable data and basic information for neuroprotective effect of genistein in Aβ25-35-induced neuronal injury.
Methods
We established an in vitro model of Alzheimer's disease by exposing primary hippocampal neurons of newborn rats to amyloid peptide 25–35 (20 μM) for 24 h and observing the effects of genistein (10 μM, 3 h) on viability, expression of ER subtypes, ChAT, NMDA receptor subunit NR2B and AMPA receptor subunit GluR2 in Aβ25-35-induced hippocampal neurons.
Results
We found that amyloid peptide 25–35 exposure reduced the viability of hippocampal neurons. Meanwhile, amyloid peptide 25–35 exposure decreased the expression of ER subtypes, ChAT and GluR2, and increased the expression of NR2B. Genistein at least partially reversed the effects of amyloid peptide 25–35 in hippocampal neurons.
Conclusion
Genistein could increase the expression of ChAT as a consequence of activating estrogen receptor subtypes, modulating the expression of NR2B and GluR2, and thereby ameliorating the status of hippocampal neurons and exerting neuroprotective effects against amyloid peptide 25–35. Our data suggest that genistein might represent a potential cell-targeted therapy which could be a promising approach to treating AD.
Background and purpose:
While it is known that breastfeeding promotes healthy brain development in children, the potential effects of formulas substantially differing in composition (ie, milk-based versus soy-based) during infancy on brain development are unclear.
Materials and methods:
Seventy-one 8-year-old children who were predominantly breastfed, milk formula fed, or soy formula fed during infancy were recruited for an MR imaging examination of the brain and a Behavior Rating Inventory of Executive Function assessment (completed via a questionnaire to the parents). Brain cortical features measured from MR imaging such as cortical thickness and surface area were extracted and compared among groups and correlated with Behavior Rating Inventory of Executive Function test scores.
Results:
Clusters in the frontal and occipital lobes showed significant differences (cluster-wise P ≤ .05, corrected for multiple comparisons) in cortical thickness or surface area among the 3 diet groups. The effects were more prominent for boys, particularly for comparison of the milk formula fed versus soy formula fed boys. Assessments of executive function and behavior showed significantly lower Behavior Rating Inventory of Executive Function test scores in soy formula fed versus milk formula fed groups, which were mostly attributed to differences in boys. There were no differences between milk formula fed and breastfed groups for either sex. Mean cortical thickness for several of the clusters in the brain showing infant diet-associated effects significantly correlated with Behavior Rating Inventory of Executive Function scores.
Conclusions:
Choices of infant diets (ie, breastfed, milk formula fed, soy formula fed) may have long-term and sex-specific effects on the cortical development and executive function and behavior of children's brains.
Background
In Alzheimer's diseases, beta-amyloid may act as prion-like protein and migrate from the gastrointestinal tract towards the brain. Soy flavonoids have been identified as neuroprotective against cognitive loss in human. Diet with soy flavonoids may be used to slow down the progression of Alzheimer's diseases.
Methods and results
We performed in-vitro tissue culture experiments using myenteric plexus longitudinal muscle layers isolated from the ileum and colon of ICR mice. Beta-amyloid can be taken up into myenteric neurons and induce neuron degeneration, which is protected by flavonoids compounds, including daidzein, genistein, glycitein and luteolin. We also administered oligomeric beta-amyloid (1–42) (total dose: 8 μg) into the gastrointestinal walls of ICR mice and conducted memory tests and gastrointestinal function assessments after 6 and 12 months. Mice treated with beta-amyloid exhibited minor learning deficits in a T-maze memory test at 6 months and significant memory impairment in a novel object recognition task at 12 months. These impairments were prevented by soy flavonoids. Tracking studies performed using fluorescently tagged beta-amyloid found that, beta-amyloid injected at the stomach can aggregate within the layer of myenteric neurons and migrate to the jejunum or via the vagus nerves to the brain after 1 month. Reductions in the gastrointestinal tissue weight and the spontaneous ileal contraction frequency were also observed at 6 and 12 months, respectively.
Conclusion
Our findings indicate that beta-amyloid can migrate from the gastrointestinal tract to the brain to induce cognitive impairments. Furthermore, chronic soy flavonoids in drinking water have protective actions.
Compared to other organs, the brain is especially exposed to oxidative stress. In general, brains from young females tend to present lower oxidative damage in comparison to their male counterparts. This has been attributed to higher antioxidant defenses and a better mitochondrial function in females, which has been linked to neuroprotection in this group. However, these differences usually disappear with aging, and the incidence of brain pathologies increases in aged females. Sexual hormones, which suffer a decrease with normal aging, have been proposed as the key factors involved in these gender differences. Here, we provide an overview of redox status and mitochondrial function regulation by sexual hormones and their influence in normal brain aging. Furthermore, we discuss how sexual hormones, as well as phytoestrogens, may play an important role in the development and progression of several brain pathologies, including neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, stroke or brain cancer.
Objective:
PhytoSERM is a selective estrogen receptor beta (ERβ) modulator comprised of three phytoestrogens: genistein, daidzein, and S-equol. The PhytoSERM formulation promotes estrogenic action in the brain while largely inactive or inhibitory in reproductive tissue. A phase Ib/IIa clinical trial (ClinicalTrial.gov ID: NCT01723917) of PhytoSERM demonstrated safety and pharmacokinetics profile of PhytoSERM. While this study was not powered for efficacy analysis, we conducted a pilot, retrospective analysis to identify potential responders to PhytoSERM treatment, and to determine the optimal populations to pursue in a phase II clinical trial of efficacy of the PhytoSERM formulation.
Methods:
In this retrospective analysis involving 46 participants (n = 16, placebo; n = 18, 50 mg/d PhytoSERM; and n = 12, 100 mg/d PhytoSERM), the therapeutic effect of PhytoSERM was stratified by 2 genetic risk modulators for Alzheimer's disease: mitochondrial haplogroup and APOE genotype.
Results:
Our retrospective responder analysis indicated that participants on 50 mg of daily PhytoSERM (PS50) for 12 weeks significantly reduced hot flash frequency compared with their baseline (mean [95% CI])-1.61, [-2.79, -0.42], P = 0.007). Participants on 50 mg of PhytoSERM also had significantly greater reduction in hot flash frequency at 12 weeks compared with the placebo group (-1.38, -0.17 [median PS50, median placebo], P = 0.04). Fifty milligrams of daily PhytoSERM also preserved cognitive function in certain aspects of verbal learning and executive function. Our analysis further suggests that mitochondrial haplogroup and APOE genotype can modify PhytoSERM response.
Conclusion:
Our data support a precision medicine approach for further development of PhytoSERM as a safe and effective alternative to hormone therapy for menopause-associated hot flash and cognitive decline. While definitive determination of PhytoSERM efficacy is limited by the small sample size, these data provide a reasonable rationale to extend analyses to a larger study set powered to address statistical significance.
Flavonoids, considered as phytoestrogen mainly deriving from fruit and vegetable, are known to have beneficial effects in brain functions. The role of flavonoids in induction of a cholinergic enzyme, acetylcholinesterase (AChE), was being explored here. In cultured PC12 cells, twenty-four commonly found flavonoids were tested for its induction on AChE activity. Fourteen flavonoids showed induction, and five of them had robust effect, i.e. daidzin, alpinetin, irisflorentin, cardamonin and lysionotin. The induction of AChE was fully blocked by pre-treatment of G15 (a selective G protein-coupled receptor 30 [GPR 30] antagonist), suggesting a direct involvement of a membrane-bound estrogen receptor, named as GPR 30, in the cultures. In addition, daidzin was further identified to induce expression of tetrameric globular form of proline-rich membrane anchor (PRiMA)-linked AChE. In parallel, application of daidzin in cultured PC12 cells significantly induced expression of neurofilaments, markers for neuronal differentiation. Taken together, flavonoids could induce the expression of AChE via GPR 30 in cultured PC12 cells, which could be a good candidate for possible treatment of the brain diseases.
The effects on memory, psychomotor functions and mood of intramuscular scopolamine (0.3 mg, 0.6 mg) were compared with those of oral lorazepam (2 mg) and placebo. Thirty-six volunteers took part in a double-blind, independent groups design. Subjects completed a battery of tests 1 and 3 h after drug administration. Both doses of scopolamine produced levels of sedation comparable to that produced by lorazepam. The time course of effects of scopolamine and lorazepam differed but the pattern of psychomotor impairments and amnestic effects produced was very similar. In terms of mood, lorazepam had an anxiolytic effect whereas scopolamine increased ratings of anxiety. Levels of sedation, indexed by either subjective ratings or motor retardation (tapping speed), were related more to psychomotor performance than to performance on memory tasks. The results suggest that benzodiazepines and scopolamine have similar amnestic and sedative effects and as such may not offer distinct models of memory dysfunction.
The effects of 6-hydroxydopamine lesions of the prefrontal cortex in monkeys were investigated on two cognitive tests of prefrontal function, spatial delayed response, and attentional set shifting. The latter test provided a componential analysis of the Wisconsin Card Sort Test, a commonly used clinical test of frontal lobe function in man. Acquisition of a visual compound discrimination requiring a shift of attention from one dimension to another (extradimensional shift), for example, shapes to lines, was significantly improved. This enhancement was behaviorally specific in that there were no effects on acquisition of a discrimination that required the continued maintenance of an attentional set toward one particular dimension (intradimensional shift), nor any effects on a series of visual or spatial discrimination reversals that involved the repeated shifting of responding between two exemplars from the same dimension. In contrast, spatial delayed response performance was impaired, in agreement with previous results. Neurochemical measures showed a marked depletion of dopamine limited to the prefrontal cortex and a smaller loss of prefrontal noradrenaline. This was accompanied by a long-term adaptive change in the striatum such that extracellular dopamine in the caudate nucleus, as measured by in vivo microdialysis, was elevated in response to potassium stimulation as long as 18 months postsurgery. It is proposed that attentional set shifting is mediated by a balanced interaction between prefrontal and striatal dopamine, and that elevated dopamine contributes to the improvement in attentional set-shifting ability. This interpretation is consistent with the impairment in attentional set-shifting ability observed in patients with Parkinson's disease or with damage to the frontal lobes using the same test as used here for infrahuman primates.
Functional MRI (fMRI) holds the promise of non-invasive mapping of human brain function in both health and disease. Yet its sensitivity and reliability for mapping higher cognitive function are still being determined. Using verbal fluency as a task, the objective was to ascertain the consistency of fMRI on a conventional scanner for determining the anatomic substrate of language between subjects and between sexes. Comparison was made with previous PET studies.
Using a 1.5 Tesla magnet and an echoplanar pulse sequence, whole brain fMRI was obtained from 12 normal right handed subjects (6 males and 6 females) as they performed a verbal fluency task.
A broadly consistent pattern of response was seen across subjects. Areas showing activation changes included the left prefrontal cortex and right cerebellum, in agreement with previous PET 15O-H2O studies. In addition, significantly decreased responses were seen in the posterior cingulate and over an extensive area of mesial and dorsolateral parietal and superior temporal cortices. The male cohort showed a slight asymmetry of parietal deactivation, with more involvement on the right, whereas the female cohort showed a small region of activation in the right orbitofrontal cortex. There were individual task related regional changes in all 12 subjects with the area showing the most significant change being the left prefrontal cortex in all cases.
Magnetic resonance scanners of conventional field strength can provide functional brain mapping data with a sensitivity at least that of PET. Activation was seen in left prefrontal and right cerebellar regions, as with PET. However, decremental responses were seen over a much larger area of the posterior cortex than had been anticipated by prior studies. The ability to see a response in each subject individually suggests that fMRI may be useful in the preinterventional mapping of pathological states, and offers a non-invasive alternative to the Wada test for assessment of hemispheric dominance. There were no gross differences in the pattern of activation between male and female subjects.
There is a need to assess the contribution of mood disorder, especially anxiety and depression, in order to understand the experience of suffering in the setting of medical practice.
Most physicians are aware of this aspect of the illness of their patients but many feel incompetent to provide the patient with reliable information. The Hospital Anxiety And Depression Scale, or HADS, was designed to provide a simple yet reliable tool for use in medical practice. The term 'hospital' in its title suggests that it is only valid in such a setting but many studies conducted throughout the world have confirmed that it is valid when used in community settings and primary care medical practice.
It should be emphasised that self-assessment scales are only valid for screening purposes; definitive diagnosis must rest on the process of clinical examination.
The aim of the present study was to investigate the influence of estrogen therapy on some psychological functions in post-menopausal women. Twenty-six subjects, all volunteers, were divided into placebo and experimental groups and examined before and after 3 months of estrogen or placebo treatment.
The effects of norepinephrine (NE) on in vitro [3H]glycogenolysis were assessed in slices of cerebral cortex from mice whose cortical noradrenergic innervation had been severely reduced by intracisternal 6-hydroxydopamine (6-OHDA) injections. A supersensitive response to NE was observed, as demonstrated by a decrease in the EC50 of the catecholamine in the lesioned mice from 533 ± 88nM to39.3 ± 7.9nM. This supersensitive response, observed two weeks after the lesion, was post-synaptic since isoproterenol, a β-adrenergic agonist not accumulated by pre-synaptic uptake mechanisms, also gave an equally supersensitive response.
Estrogen treatment of postmenopausal women has been suggested to improve mood and psychological function. However, this remains controversial because previous studies involved heterogeneous groups, were not double blind, and included women who were also experiencing somatic symptoms that were relieved by estrogen. A randomized double-blind study was carried out comparing the effects of placebo and conjugated equine estrogens (0.625 and 1.25 mg) on psychological function over 3 months in 36 asymptomatic women, aged 45-60. The tests included the Minnesota Multiphasic Personality Inventory-168, the Profile of Adaptation to Life, and the Beck Depression Inventory. Memory was assessed directly by the Wechsler Adult Intelligence Scales, measuring both digit span and digit symbol. All women were well-adjusted psychologically. The income management scale of the Profile of Adaptation to Life improved (P less than .05) with estrogen, as did the Beck Depression Inventory (P less than .05), but these results were not dose-related. Memory assessed prospectively by the Wechsler Adult Intelligence Scales was not affected significantly. These results suggest that estrogen use may improve the overall quality of life in postmenopausal women.
It is notoriously difficult to assess the contribution of the sedative effects of benzodiazepines to the cognitive impairments that they produce. The purpose of the present experiment was to determine whether a similar pattern of cognitive impairment would be seen in conditions when subjects felt equally sleepy as the result of sleep deprivation. The effects of a sedative dose of lorazepam (2.5 mg) in healthy volunteers was therefore compared with the effects of acute sleep deprivation (a night on-call) in a group of junior doctors and the effects of chronically disturbed sleep due to snoring. Lorazepam, acute sleep deprivation, and chronic sleep disturbance all significantly increased subjective sedation. In addition, lorazepam significantly impaired performance in two tests of psychomotor speed and caused significant anterograde amnesia. Semantic and short-term memory were not impaired by lorazepam, nor was there any impairment in executive function. The only deficit found following acute sleep deprivation was in a test of semantic memory, generating examples from a difficult category. The only significant deficit in the group suffering from chronically disturbed sleep, compared with age-matched controls, was in executive function, and there was a nearly significant impairment in sustained attention. These results suggest that, despite the common factor of increased subjective sedation, the profile of cognitive impairment in the two sleep deprivation groups are neither similar to each other nor to that seen following an acute dose of lorazepam.
The N-methyl D-aspartate receptor complex is involved in the mechanism of long-term potentiation, which is thought to be the biological basis of learning and memory. This complex can be manipulated in a number of ways, one of which is through the strychnine-insensitive glycine receptor coagonist site. The effects of Bioglycin(Konapharma, Pratteln, Switzerland), a biologically active form of the amino acid glycine, were therefore studied in healthy students (mean age, 20.7 years) and middle-aged men (mean age, 58.9 years) with tests that measured attention, memory and mood, using a double-blind, randomized, crossover design. Compared with the young group, the middle-aged group had significantly poorer verbal episodic memory, focused, divided, and sustained attention; they also differed in their subjective responses at the end of testing. Bioglycin significantly improved retrieval from episodic memory in both the young and the middle-aged groups, but it did not affect focused or divided attention. However, the middle-aged men significantly benefited from Bioglycin in the sustained-attention task. The effects of Bioglycin differed from those of other cognitive enhancers in that it was without stimulant properties or significant effects on mood, and it primarily improved memory rather than attention. It is likely to be of benefit in young or older people in situations where high retrieval of information is needed or when performance is impaired by jet lag, shift work, or disrupted sleep. It may also benefit the impaired retrieval shown in patients with schizophrenia, Parkinson's disease, and Huntington's disease.
The Turner syndrome (TS) phenotype is characterized by a specific neurocognitive profile of normal verbal skills, impaired visual-spatial and visual-perceptual abilities, and impaired nonverbal more than verbal memory. We compared verbal and nonverbal memory in estrogen- and placebo-treated girls with TS (ages 7 to 9 years) and age-matched female controls.
Children received either estrogen (ethinyl estradiol, 25 ng/kg/d) or placebo for 1 to 3 years (mean, 2.1+/-0.9 years) in a randomized, double-blind study. Memory and language tasks administered included the Wechsler Intelligence Scale for Children-Revised, Digit Span (forward and backward), the Children's Word List, the Denman Paragraph, the Peabody Picture Vocabulary Test, Boston Naming, immediate and delayed Recall of the Rey Complex Figure, Nonword Reading, Wide Range Achievement Test-Revised reading subtest, Verbal fluency, and the Token Test.
The estrogen-treated TS group performed better than the placebo-treated TS group for the Children's Word List immediate and delayed recall and the Digit Span backwards test (p<0.01 to 0.04), although the results were not significant after adjusting for multiple comparisons. The placebo-treated TS group performed less well than the controls for recall of Digit Span backward (p<0.0001; placebo-treated, 2.8+/-1.3; estrogen-treated, 3.4+/-1.2; and controls, 4.2+/-1.3) and immediate and delayed recall of the Children's Word List (delayed recall, p<0.0001; placebo-treated, 6.2+/-3.1; estrogen-treated, 8.0+/-2.9; and controls, 9.0+/-2.9). Performance for these measures was similar for the estrogen-treated TS group and the control group.
Estrogen replacement therapy in young girls with Turner Syndrome is associated with improved verbal and nonverbal memory. The optimal patient age, dose, and duration of estrogen replacement require further study.
To provide exploratory analyses of associations between levels of several sex hormones and cognitive performance in elderly women.
Sex steroid hormones are implicated in the cognitive processes of the adult brain. Comparing cognitive performance across or between conditions associated with different hormone levels, such as phases of the menstrual cycle, surgical menopause, and estrogen replacement therapy suggests conditions with higher levels of estrogen are associated with better verbal memory and possibly worse visuospatial ability.
The authors measured circulating sex hormone levels in 39 highly educated, nondemented, predominantly white elderly women. Levels were correlated with neuropsychological performance, controlling for age, education, frequency of prior testing, use of estrogen replacement, and depression.
High estradiol levels were associated with better delayed verbal memory and retrieval efficiency, whereas low levels were associated with better immediate and delayed visual memory. Levels of testosterone were related positively to verbal fluency. Levels of progesterone and androstenedione were unrelated to cognitive performance.
Both estrogen and testosterone showed associations with cognitive performance. Estrogen may enhance, and depress, specific cognitive skills.
Verbal fluency tests (VFTs) are suggested to assess frontal lobe function. This view is supported by functional imaging studies that report left frontal activation during VFTs. VFTs require retrieval of semantically associated words from long-term memory storage. The neural networks that participate in this process, however, are largely unknown. These neural networks are of interest, given that patients with early Alzheimer's disease, typically without frontal pathology, are often impaired in VFTs. In the present study, functional magnetic resonance imaging was performed to determine brain activation areas during VFTs in young subjects. In the activation task, category fluency was contrasted with orderly listing of numbers. As judged from using this comparison, there was activation in the left medial temporal lobe, in the inferior frontal and retrosplenial cortices bilaterally, and in the left superior parietal lobule. Left medial temporal lobe activation was present in 13 of the 14 study subjects either in the hippocampal formation (11 of 14) or in the posterior parahippocampal gyrus (12 of 14). These results suggest that the medial temporal lobe is required for the process of retrieval by category. Functional magnetic resonance imaging combined with a category fluency task may provide a new method to study patients with early Alzheimer's disease.
Estrogen concentrations decline with age and menopause is often followed by an acceleration of the age effects on cognition. It is suggested that replacement of estrogen would reinstate, at least in part, cognitive abilities. Effects of estrogens on memory have been reported in studies with women in a clinical setting who either needed or wished to have the estrogen replacement and are mostly in the perimenopausal age-band.
The present study investigated the effects of estradiol on memory and on frontal lobe function in elderly female subjects who did not suffer any of the postmenopausal symptoms and had never taken estrogen hormone replacement (EHR) previously.
EHR (Progynova TS, transdermal estradiol; n=19) or placebo (n=18) was given for a period of 3 weeks to elderly healthy female subjects. Memory, frontal lobe functions (inhibition and planning) and visuospatial abilities (mental rotation) were tested before and after treatment. Estrogen plasma levels were measured to confirm the result of EHR. Cortisol plasma levels were also measured before and after cognitive performance in order to evaluate the effects of EHR on the sensitivity of the hypothalamo-pituitary-adrenal (HPA) axis to mild mental stress.
Plasma estradiol levels in the drug group increased to levels equivalent to that of a fertile woman (0.21+/-0.5 nmol/l). Memory function as well as visuospatial abilities as measured by a mental rotation task improved significantly with EHR. However, there was no effect of EHR on frontal lobe functions. The cognitive effects were not dependent on an improvement in mood or general well-being as may be the case with EHR in women at peri- or post-menopausal stage. EHR was found to increase the HPA response to task-induced stress, as indicated by an increase in cortisol plasma levels.
The present study has provided evidence of a beneficial effect of EHR on cognitive abilities given for first time to healthy elderly women. Furthermore, the present study has demonstrated a differential effect of EHR on memory, visuospatial abilities and frontal lobe function.
Oxidative damage to lipids may be involved in the etiology of atherosclerosis, cardiovascular disease in general, and cancer. The soy isoflavone phytoestrogens, genistein and daidzein, and equol (a daidzein metabolite produced by intestinal microflora) are antioxidants in vitro; equol is a particularly good inhibitor of LDL oxidation and membrane lipid peroxidation.
We sought to investigate the effects of a diet enriched with soy containing isoflavones on in vivo biomarkers of lipid peroxidation and resistance of LDL to oxidation, compared with a diet enriched with soy from which the isoflavones had been extracted.
: A randomized, crossover design was used to compare diets enriched with soy that was low or high in isoflavones in 24 subjects. Plasma concentrations of an F(2)-isoprostane, 8-epi-prostaglandin F(2)(alpha) (8-epi-PGF(2)(alpha)), a biomarker of in vivo lipid peroxidation, and resistance of LDL to copper-ion-induced oxidation were determined.
Plasma concentrations of 8-epi-PGF(2)(alpha) were significantly lower after the high-isoflavone dietary treatment than after the low-isoflavone dietary treatment (326 +/- 32 and 405 +/- 50 ng/L, respectively; P = 0.028) and the lag time for copper-ion-induced LDL oxidation was longer (48 +/- 2.4 and 44 +/- 1.9 min, respectively; P = 0.017). Lag time for oxidation of unfractionated plasma and plasma concentrations of malondialdehyde, LDL alpha-tocopherol, polyunsaturated fatty acids, and isoflavonoids did not differ significantly between dietary treatments.
Consumption of soy containing naturally occurring amounts of isoflavone phytoestrogens reduced lipid peroxidation in vivo and increased the resistance of LDL to oxidation. This antioxidant action may be significant with regard to risk of atherosclerosis, cardiovascular disease in general, and cancer.
Estrogen replacement therapy (ERT) may help maintain normal cognitive function. Nondemented surgically menopausal women on ERT (n = 10) enrolled in a longitudinal aging study performed better than age- and education-matched control subjects (n = 25) on selected tests of verbal memory and constructional ability. These results suggest that ERT initiated soon after surgical menopause can have long-term neuroprotective effects in cognitively intact women.
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