***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: In healthy older adults , resveratrol supplementation has been shown to improve long-term glucose control , resting-state functional connectivity ( RSFC ) of the hippocampus , and memory function . Here , we aim ed to investigate if these beneficial effects extend to individuals at high-risk for dementia , i.e. , patients with mild cognitive impairment ( MCI ) . In a r and omized , double-blind interventional study , 40 well-characterized patients with MCI ( 21 females ; 50–80 years ) completed 26 weeks of resveratrol ( 200 mg/d ; n = 18 ) or placebo ( 1,015 mg/d olive oil ; n = 22 ) intake . Serum levels of glucose , glycated hemoglobin A1c and insulin were determined before and after intervention . Moreover , cerebral magnetic resonance imaging ( MRI ) ( 3 T ) ( n = 14 vs. 16 ) was conducted to analyze hippocampus volume , microstructure and RSFC , and neuropsychological testing was conducted to assess learning and memory ( primary endpoint ) at both time points . In comparison to the control group , resveratrol supplementation result ed in lower glycated hemoglobin A1c concentration with a moderate effect size ( ANOVARM p = 0.059 , Cohen 's d = 0.66 ) , higher RSFC between right anterior hippocampus and right angular cortex ( p < 0.001 ) , and led to a moderate preservation of left anterior hippocampus volume ( ANOVARM p = 0.061 , Cohen 's d = 0.68 ) . No significant differences in memory performance emerged between groups . This proof-of-concept study indicates for the first-time that resveratrol intake may reduce glycated hemoglobin A1c , preserves hippocampus volume , and improves hippocampus RSFC in at-risk patients for dementia . Larger trials with longer intervention time should now determine if these benefits can be vali date d and extended to cognitive function Introduction : The polyphenol resveratrol has been suggested to exert beneficial effects on memory and the aging hippocampus due to calorie‐restriction mimicking effects . However , the evidence based on human interventional studies is scarce . We therefore aim ed to determine the effects of resveratrol on memory performance , and to identify potential underlying mechanisms using a broad array of blood‐based biomarkers as well as hippocampus connectivity and microstructure assessed with ultra‐high field magnetic resonance imaging ( UHF‐MRI ) . Methods : In this double‐blind , r and omized controlled trial , 60 elderly participants ( 60–79 years ) with a wide body‐mass index ( BMI ) range of 21–37 kg/m2 were r and omized to receive either resveratrol ( 200mg/day ) or placebo for 26 weeks ( registered at Clinical Trials.gov : NCT02621554 ) . Baseline and follow‐up assessment s included the California Verbal Learning Task ( CVLT , main outcome ) , the ModBent task , anthropometry , markers of glucose and lipid metabolism , inflammation and neurotrophins derived from fasting blood , multimodal neuroimaging at 3 and 7 T , and question naires to assess confounding factors . Results : Multivariate repeated‐ measures ANOVA did not detect significant time by group effects for CVLT performance . There was a trend for preserved pattern recognition memory after resveratrol , while performance decreased in the placebo group ( n.s . , p=0.07 ) . Further exploratory analyses showed increases in both groups over time in body fat , cholesterol , fasting glucose , interleukin 6 , high sensitive C‐reactive protein , tumor necrosis factor alpha and in mean diffusivity of the subiculum and presubiculum , as well as decreases in physical activity , brain‐derived neurotrophic factor and insulin‐like growth factor 1at follow‐up , which were partly more pronounced after resveratrol . Discussion : This interventional study failed to show significant improvements in verbal memory after 6 months of resveratrol in healthy elderly with a wide BMI range . A non‐significant trend emerged for positive effects on pattern recognition memory , while possible confounding effects of unfavorable changes in lifestyle behavior , neurotrophins and inflammatory markers occurred . Our findings also indicate the feasibility to detect (un)healthy aging‐related changes in measures of hippocampus microstructure after 6 months using 7 T diffusion MRI . More studies incorporating a longer duration and larger sample size are needed to determine if resveratrol  enhances memory performance in healthy older adults . HIGHLIGHTSIn this r and omized clinical trial , 6 months resveratrol supplementation showed no significant effects on verbal memory  compared to placebo . Unfavorable changes in lifestyle factors at follow‐up might have introduced confounding . Secondary analyses showed a trend towards preserved pattern recognition . We used multimodal ultra high field MRI to detect subtle changes in microstructure of hippocampus subfields Rationale There has recently been increasing interest in the potential of flavanols , plant-derived compounds found in foods such as fruit and vegetables , to ameliorate  age-related cognitive decline .  Research suggests that cocoa flavanols improve memory and learning , possibly as a result of their anti-inflammatory and neuroprotective effects . These effects may be mediated by increased cerebral blood flow ( CBF ) , thus , stimulating neuronal function . Objectives The present study employed arterial spin labelling functional magnetic resonance imaging to explore the effect of a single acute dose of cocoa flavanols on regional CBF . Methods CBF was measured pre- and post-consumption of low ( 23 mg ) or high ( 494 mg ) 330 ml equicaloric flavanol drinks matched for caffeine , theobromine , taste and appearance according to a r and omized counterbalanced crossover double-blind design in eight males and ten females , aged 50–65 years .  Changes in perfusion from pre- to post-consumption were calculated as a function of each drink . Results Significant increases in regional perfusion across the brain were observed following consumption of the high flavanol drink relative to the low flavanol drink , particularly in the anterior cingulate cortex and the central opercular cortex of the parietal lobe . Conclusions Consumption of cocoa flavanol improves regional cerebral perfusion in older adults . This provides evidence for a possible acute mechanism by which cocoa flavanols are associated with benefits for cognitive performance BACKGROUND The many putative beneficial effects of the polyphenol resveratrol include an ability to bolster endogenous antioxidant defenses , modulate nitric oxide synthesis , and promote vasodilation , which thereby improves blood flow . Resveratrol may therefore modulate aspects of brain function in humans . OBJECTIVE The current study assessed the effects of oral resveratrol on cognitive performance and localized cerebral blood flow variables in healthy human adults . DESIGN In this r and omized , double-blind , placebo-controlled , crossover study , 22 healthy adults received placebo and 2 doses ( 250 and 500 mg ) of trans-resveratrol in counterbalanced order on separate days . After a 45-min resting absorption period , the participants performed a selection of cognitive tasks that activate the frontal cortex for an additional 36 min . Cerebral blood flow and hemodynamics , as indexed by concentration changes in oxygenated and deoxygenated hemoglobin , were assessed in the frontal cortex throughout the posttreatment period with the use of near-infrared spectroscopy . The presence of resveratrol and its conjugates in plasma was confirmed by HPLC after the same doses in a separate cohort ( n = 9 ) . RESULTS Resveratrol administration result ed in dose-dependent increases in cerebral blood flow during task performance , as indexed by total concentrations of hemoglobin . There was also an increase in deoxyhemoglobin after both doses of resveratrol , which suggested enhanced oxygen extraction , that became apparent toward the end of the 45-min absorption phase and was sustained throughout task performance . Cognitive function was not affected . Resveratrol metabolites were present in plasma throughout the cognitive task period . CONCLUSION These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables Flavanol consumption is favorably associated with cognitive function . We tested the hypothesis that dietary flavanols might improve cognitive function in subjects with mild cognitive impairment . We conducted a double-blind , parallel arm study in 90 elderly individuals with mild cognitive impairment r and omized to consume once daily for 8 weeks a drink containing ≈990 mg ( high flavanols ) , ≈520 mg ( intermediate flavanols ) , or ≈45 mg ( low flavanols ) of cocoa flavanols per day . Cognitive function was assessed by Mini Mental State Examination , Trail Making Test A and B , and verbal fluency test . At the end of the follow-up period , Mini Mental State Examination was similar in the 3 treatment groups ( P=0.13 ) . The time required to complete Trail Making Test A and Trail Making Test B was significantly ( P<0.05 ) lower in subjects assigned to high flavanols ( 38.10±10.94 and 104.10±28.73 seconds , respectively ) and intermediate flavanols ( 40.20±11.35 and 115.97±28.35 seconds , respectively ) in comparison with those assigned to low flavanols ( 52.60±17.97 and 139.23±43.02 seconds , respectively ) . Similarly , verbal fluency test score was significantly ( P<0.05 ) better in subjects assigned to high flavanols in comparison with those assigned to low flavanols ( 27.50±6.75 versus 22.30±8.09 words per 60 seconds ) . Insulin resistance , blood pressure , and lipid peroxidation also decreased among subjects in the high-flavanol and intermediate-flavanol groups . Changes of insulin resistance explained ≈40 % of composite z score variability through the study period ( partial r2=0.4013 ; P<0.0001 ) . To the best of our knowledge , this is the first dietary intervention study demonstrating that the regular consumption of cocoa flavanols might be effective in improving cognitive function in elderly subjects with mild cognitive impairment . This effect appears mediated in part by an improvement in insulin sensitivity Previous research has shown that resveratrol can increase cerebral blood flow ( CBF ) in the absence of improved cognitive performance in healthy , young human subjects during the performance of cognitively dem and ing tasks . This lack of cognitive effects may be due to low bioavailability and , in turn , reduced bioefficacy of resveratrol in vivo . Piperine can alter polyphenol pharmacokinetics , but previous studies have not investigated whether this affects the efficacy of the target compound . Therefore , the objective of the present study was to ascertain whether co-supplementation of piperine with resveratrol affects the bioavailability and efficacy of resveratrol  with regard to cognition and CBF . The present study utilised a r and omised , double-blind , placebo-controlled , within-subjects design , where twenty-three adults were given placebo , trans-resveratrol ( 250 mg ) and trans-resveratrol with 20 mg piperine on separate days at least a week apart . After a 40 min rest/absorption period , the participants performed a selection of cognitive tasks and CBF was assessed throughout the period , in the frontal cortex , using near-IR spectroscopy . The presence of resveratrol and its conjugates in the plasma was confirmed by liquid chromatography-MS analysis carried out following the administration of the same doses in a separate cohort ( n 6 ) . The results indicated that when co-supplemented , piperine and resveratrol significantly augmented CBF during task performance in comparison with placebo and resveratrol alone . Cognitive function , mood and blood pressure were not affected . The plasma concentrations of resveratrol and its metabolites were not significantly different between the treatments , which indicates that co-supplementation of piperine with resveratrol enhances the bioefficacy of resveratrol with regard to CBF effects , but not cognitive performance , and does this without altering bioavailability The dentate gyrus ( DG ) is a region in the hippocampal formation whose function declines in association with human aging and is therefore considered to be a possible source of age-related memory decline . Causal evidence is needed , however , to show that DG-associated memory decline in otherwise healthy elders can be improved by interventions that enhance DG function . We addressed this issue by first using a high-resolution variant of functional magnetic resonance imaging ( fMRI ) to map the precise site of age-related DG dysfunction and to develop a cognitive task whose function localized to this anatomical site . Then , in a controlled r and omized trial , we applied these tools to study healthy 50–69-year-old subjects who consumed either a high or low cocoa flavanol – containing diet for 3 months . A high-flavanol intervention was found to enhance DG function , as measured by fMRI and by cognitive testing . Our findings establish that DG dysfunction is a driver of age-related cognitive decline and suggest non-pharmacological means for its amelioration We tested whether chronic supplementation with resveratrol ( a phytoestrogen ) could improve cerebrovascular function , cognition and mood in post-menopausal women . Eighty post-menopausal women aged 4 
    Output:
    
As it emerges from this systematic review , the use of some phytochemicals and botanicals seems to be very promising in order to delay the onset and progression of neurodegenerative and other age‐related diseases .