Polyphenols and cognitive decline prevention -
Funnel plot for available study results for EM. Note that sample size in the subgroup meta-analyses was considerably reduced. Based on this systematic review of 66 reported RCTs testing the effects of polyphenols on memory, 33 studies found a significant improvement on at least one memory outcome measure after polyphenol administration, while 30 did not find any significant effects, and three reported a worsening compared to control condition.
Reporting was based on a variety of WM and EM outcome measures, of which a selection only were reported as significantly improved after polyphenol consumption compared to placebo with, if reported, small to large effect sizes. Considering the available and calculated effect sizes from available outcomes of 49 studies representing core WM and EM measures, pooled meta-analyses supported a small positive effect on both WM and EM with a mean effect size of 0.
However, Funnel plot asymmetry tests detected a significant positivity bias for both WM and EM meta-analysis, questioning the validity of results. When excluding studies with very large positive effects, though, meta-analyses remained significant for a small effect.
Our review further indicated a large heterogeneity between studies and outcomes studied, in terms of polyphenol formula and exact memory test used, study duration, sample size and characteristics, as well as considering statistical variance in effects sizes.
The evaluated studies can be summarized to show a small positive effect on both WM and EM with similar estimates, however, note that this finding needs to be interpreted with caution due the indicated positivity bias in reporting of polyphenol studies.
Still, it has been argued that polyphenols might improve brain function. For example, Brickman et al. When high cocoa-flavanol consumption was compared to low consumption, the middle part i. The activation was also associated with higher memory performance.
It should be noted though, that this study was performed in a small sample of 37 participants divided into two groups. The hippocampus is necessary for accessing short-term memory representations during WM tasks 20 , 96 , and hippocampal and parahippocampal areas, parts of the medial temporal lobe MTL , are critically involved in EM for encoding and retrieval 20 , 96 , whereas MTL lesions do not lead to extreme WM performance degradation.
Later studies however indicated the involvement of the MTL in WM tasks, especially when associations e. Future studies involving neuroimaging techniques could help to further understand the neurobiological mechanisms underlying potential benefits of polyphenols on WM and EM.
In this review, we did not observe strong systematic associations between memory improvement and sample size, study duration and mean age. Indeed, significant results were found in studies with long-term follow-up assessment after 2.
Additionally, bigger sample sizes, and thus greater power to detect an effect that is present did not result in more in significant findings. Also, the mean age of the samples did not systematically lead to significant or insignificant study results, however, some differences were observed regarding study population and polyphenol subclass.
Overall, results of the polyphenol subclasses were mixed. The percentage of significant memory outcome measures for Ginkgo biloba , other polyphenol-rich extracts, flavonoids, phenolic acids, and stilbenes were relatively similarly distributed, while sub-group meta-analyses in polyphenol subclasses that could include five outcomes or more failed to show significant benefits for Ginkgo biloba , flavanol and soy isoflavones.
Here, probability of positivity bias was markedly reduced, indicating a higher confidence in the results though note the considerably smaller number of studies included in the sub-analyses.
Some support for the expected significant positive effects were found for flavonoids, anthocyanins and resveratrol. In addition, within the polyphenol subclasses, efficiency was sometimes dependent on study dosage.
For example, it can be speculated that the dosages in the studies administering Ginkgo biloba extract, namely between The polyphenol dosages for Pinus radiata bark extract and spearmint extract were higher, namely mg flavonoids per day and mg polyphenols per day, respectively.
Also, inter-individual differences in polyphenol absorption, metabolism, and excretion might be other reasons of diverging study results.
For instance, Bensalem et al. Possibly, polyphenol supplementation in the group with the highest amount of cognitive decline compensates for the lower intake and higher excretion, leading to improved memory performances in people with more severe memory decline.
However, as sample characteristics, exact polyphenol formulas and dosages varied considerably between studies, as well as metabolomics of polyphenols were seldomly reported, results are difficult to harmonize in this regard. However note that as most extracts in the reviewed studies provided a mixture of polyphenolic molecules, a detailed cause-response investigation with regard to memory function seemed difficult.
Future studies should incorporate blood-based biomarkers of individual polyphenol availability and metabolism, to further understand potential differential effects of polyphenol subclasses on cognitive performance.
This underlines the difficulty to differentiate results between non-pathological and pathological aging populations. Considering results of subgroup meta-analyses, however, polyphenols seemed to exert positive effects in MCI and AD or vascular dementia patients on WM, but not significantly on EM, in contrast to meta-analyses in healthy groups.
In addition, studies in older women only could not show significant improvements on average, yet, this might be also due to a lack of effects of isoflavonols, as this was the polyphenol used in most of these studies.
Another interpretation is that both Ginkgo biloba and soy isoflavones had attracted probably the most interest in the last decades as a dietary supplement to combat cognitive decline, potentially due to certain hypes around alternative, nutrition-guided medicine approaches and to the estrogenic action attributed to isoflavones.
Thus, these polyphenols were studied most extensively in the literature also with larger, longer-term and high-quality RCTs, leading to a more balanced reporting and resulting partly null findings, which would fit to some of the subgroup meta-analyses.
Still, differences in sample age, pathology and gender between studies could have contributed to mixed results.
For example, positive effects of Pinus radiata bark and spearmint extracts were found in relatively young age, while no effects were seen in samples that were on average 10—25 years older.
Moreover, on study that could not demonstrate any positive effect, meaning no objective or subjective effect, of a polyphenol-rich extract on memory, was performed in the oldest sample This was a sample consisting of patients with dementia or age-associated memory impairment.
Consequently, it is possible that polyphenols are more effective in relatively young and unaffected samples, but less effective in older patient samples.
In addition, menopause in women is associated with an increased risk for developing metabolic syndrome, known for disturbances in glucose metabolism It has been hypothesized that the negative consequences of cardiovascular risk factors on memory performance, for example higher glucose levels, can be compensated by certain polyphenols such as resveratrol administration due to regulation of glucose metabolism and insulin sensitivity , rendering a possible efficacy of polyphenols in postmenopausal women likely.
In a previous study in older adults, we found that resveratrol lowered glycated hemoglobin A1c in blood, a long-term marker of glucose, which was associated with improved functional connectivity of the hippocampus with the medial prefrontal cortex and eventually memory retention Also, reductions in insulin after cocoa flavonols correlated with increases in memory performance, supporting a potential link between polyphenols and insulin sensitivity as beneficial mechanism However, samples were often not fully characterized with regard to cardiovascular and metabolic health as well as brain diseases, i.
Future studies with larger, more diverse samples and sensitive monitoring of cardiovascular, metabolic and beginning brain pathologies are needed to better understand the impact of age, beginning pathologies, and gender on polyphenol action.
Several mechanisms have been proposed that might underly the beneficial effects of polyphenols on brain aging. These include anti-oxidative and anti-inflammatory mechanisms and improvements in cardiovascular health such as lower blood pressure and better insulin sensitivity, which are all related to better brain structure and function.
Pinus radiata bark extract, for example, has been discussed to inhibit oxidation, to reduce systolic blood pressure and to modify signaling in the brain due to the ability of polyphenol metabolites to cross the blood-brain barrier The reduction of oxidation byproducts in the hippocampus has been suggested as a possible mechanism of spearmint extract Moreover, a recent meta-analysis of carotenoids, known to exert anti-oxidant properties in vitro and in vivo , provides evidence for a positive effect of carotenoids on improving cognitive performance in middle-aged and older adults, further supporting the hypothesis of a causal role of antioxidant actions in the beneficial effect of plant-derived nutrients on brain health A reduction in pro-inflammatory markers has for instance been observed after anthocyanin-rich supplements, thereby improving hippocampus-dependent memory performance.
Kent et al. Yet, significantly lower systolic blood pressure was found by Kent et al. For more details on suggested mechanistic pathways linking specific nutrients to cognitive function in aging please see other reviews [e. Several limitations of this review should be considered.
First, several studies could not be added to our meta-analysis due to lack of raw values, specific information or unplausibility in the given tables, limiting interpretability.
Second, only one search base was included PubMed , due to the limited access to Cochrane and EMBOS library, leading to a risk of omitting published study results. In addition, the results of the different types of polyphenols on WM and EM should be interpreted with care, since the number of studies per polyphenol subclass or extract was still relatively small.
Only a few studies reported test validity and low construct validity might lead to drawing incorrect conclusions from the results.
These factors might have contributed to the large statistical heterogeneity observed in the meta-analyses, and reported findings given in the systematic review may not withstand a tight control of type-1 error in the individual studies, in line with the often detected probable positivity bias.
In addition, we did not evaluate included studies on study quality e. Also, doses of the different polyphenols were barely comparable and not harmonized at all. All studies reported daily-administered amounts, but the effect of a specific dose of for example isoflavone is hard to compare with the effect of the same amount of flavanol, and compliance measures often relied on self-report or capsule count once at the end of studies.
In general, effect sizes in nutrition sciences and lifestyle interventions are expected to be rather small due to confounding factors in a free-living population. In contrast to other fields, lifestyle interventions have a long tradition of being pre-registered, e. gov and nowadays also on osf.
io, which enables to restrict the number of post-hoc statistical testing and the possibility to report null or negative findings. Indeed, effect sizes in pre-registered studies were shown to be smaller in pre-registered studies compared to non-pre-registered studies Therefore, the herein presented results of a significant effect for EM and WM are likely to be expected and indeed representative of the field.
Future studies should harmonize control conditions and use memory tests with high construct validity and focus on the quality of the methods. Methodological quality can be increased by for example concealment of allocation, using an intention-to-treat analysis, and measuring compliance as well as implementing memory tests that are insensitive to ceiling or test-retest effects, such as the computerized administration of the Mnemonic Similarity Task Moreover, future studies should include larger samples and longer follow-up to increase power.
Yet, the sample sizes and durations of the RCTs included in this review did not seem to affect the results. By including biological parameters, such as urine or blood samples, and functional and structural brain measures using e.
Performing longer longitudinal studies in the future could provide insight into whether the consumption of polyphenols decreases progression rates of patients with mild neurocognitive disorder to dementia.
Based on reviewing 66 short- to longer-duration daily polyphenol intervention RCTs with small to large sample sizes, a beneficial effect of polyphenols on WM and EM in middle-aged to older adults may be considered small on average, according to qualitative review and a pooled meta-analysis of all available outcomes of 49 studies.
The reported outcome measures largely varied and some studies of longer duration and larger sample sizes did not report any significant memory improvement after polyphenol administration. We also noted strong evidence for reporting bias and the statistical heterogeneity was considerably large between studies.
Thus interpretation warrants caution and needs to be confirmed by further research. Future studies are encouraged to harmonize polyphenol formulas and doses as well as neuropsychological test methodology, and to increase sample sizes and follow-up periods. Overall, dietary supplementation studies investigating diet-effects on memory of high quality do exist, however, suffer from known limitations in the field and the problem to investigate rather small expected effects.
The original contributions presented in the study are included in the article as meta-data. Further inquiries related to effect sizes per study or other queries can be directed to the corresponding author. KV, EM, and AVW: conceptualization and data analysis.
KV and AVW: conducted literature search. KV: first draft. EM and AVW: visualization. EM, AVW, and AK: review and correction. All authors contributed to the article and approved the submitted manuscript. This work was supported by grants of the German Research Foundation No.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.
Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. United Nations, Department of Economic and Social Affairs. World Population Prospects Google Scholar.
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Please enable Javascript for this site to function properly. In navigation section. Select this link to jump to content Menu. Search Search. Published between: Published from year: and Published to year: Search syntax help. In content section. Select this link to jump to navigation Abstract Background: There is increasing interest in the impact of dietary influences on the brain throughout the lifespan, ranging from improving cognitive development in children through to attenuating ageing related cognitive decline and reducing risk of neurodegenerative diseases.
Objective: The purpose of this overview is to synthesise and evaluate the best available evidence from two sources, namely meta-analyses and systematic reviews, in order to give an accurate reflection of the current evidence base for an association between polyphenols and cognitive benefits.
Method: Four meta-analyses and thirteen systematic reviews published between — were included, and were categorised according to whether they reviewed specific polyphenol-rich foods and classes or all polyphenols. Results: A clear and consistent theme emerged that whilst there is support for an association between polyphenol consumption and cognitive benefits, this conclusion is tentative, and by no means definitive.
Conclusions: Further research is required to strengthen the reliability of the evidence base. Table 1 Summary of meta-analyses and systematic reviews published between — selected for inclusion alphabetised by polyphenol, then author.
Text Box 1. Table 2 For reviews of individual polyphenol-rich foods or specific sub-classes, a summary of the evidence base available for efficacy in specific populations, doses, duration of intervention, and cognitive domains. Text Box 2. WHAT DO WE MEAN BY A COGNITIVE BENEFIT? Table 3 —Hypothetical methods for defining a cognitive benefit associated with polyphenol consumption.
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Built on the Scolaris platform by:. Good to excellent quality Physiotherapy Evidence Database Scale PEDro. No evidence of bias with multiple methods. Meta-analysis did not find supportive effects.
The systematic review provided evidence that polyphenols may benefit cognition in older adults. Sufficient quality 6. Not sufficient evidence to confirm that polyphenols have beneficial effects against AD.
Insufficient evidence to recommended polyphenol consumption for prevention of cognitive decline. Evidence for improved cognitive function or neuroimaging benefits when consumed chronically.
Benefits of anthocyanins are promising with six of seven studies reporting improvements in either single, or multiple, cognitive outcomes. Benefits for memory and executive function in children, older adults and adults with mild cognitive impairment. Tentative support for a benefit to memory, but limited by methodological heterogeneity.
RCTs of chocolate, cocoa, proanthocyanidins, flavanols or epicatechin, healthy ppts. Stronger evidence from studies of higher quality with compound matched placebos. Double-blind, RCTs, min. duration of 4 weeks, older adults undefined published after Jan Benefits found in three of five studies in healthy older adults.
However, insufficient evidence to support curcumin as a treatment for cognitive decline. Memory benefits in healthy older adults but no benefit for AD patients.
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Hypoglycemia in elderly individuals for just a few Fertility diet plan should preventuon enough to fecline started. If you ptevention to make more complex Polyphenols and cognitive decline prevention, use the tips below cgonitive guide you. A growing body Polyphenols and cognitive decline prevention evidence suggests that Poylphenols interventions may delay or halt the progression of age-related health disorders and cognitive decline. Among the components of the human diet, polyphenols from berries are essential micronutrients that have been particularly studied for improving cognitive functions. In the present review, we highlight the health impact of major polyphenolic classes found in berries: flavanols, anthocyanins and stilbenes, focusing on resveratrol. The reports of beneficial effects of berry consumption on age-related cognitive decline and associated neurobiological processes in animals and human are underscored. Norwich Medical School, James Watson Road, University of Polyphenols and cognitive decline prevention Natural cholesterol solution, Norwich Research Park, Norwich NR4 7UQ, UK. Polyphenols and cognitive decline prevention Healthy snacks for diabetics. Received: 13 February Accepted: 24 Polyphdnols Cognitivr evidence prevntion that diet and lifestyle can play an prwvention role in delaying the onset or halting the progression of age-related health disorders and to improve cognitive function. A growing number of dietary intervention studies in humans and animals and in particular those using polyphenol-rich diets have been proposed to exert a multiplicity of neuroprotective actions within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation and a potential to promote memory, learning, and cognitive functions.
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