A preliminary study of the safety, feasibility and cognitive efficacy of soy isoflavone supplements in older men and women. Effects of resveratrol on memory performance, hippocampus connectivity and microstructure in older adults – A randomized controlled trial The effect of flavanol-rich cocoa on cerebral perfusion in healthy older adults during conscious resting state: a placebo controlled, crossover, acute trial Effects of blackcurrant-based juice on atherosclerosis-related biomarkers in cultured macrophages and in human subjects after consumption of a high-energy meal. Effects of Pomegranate Juice Supplementation on Oxidative Stress Biomarkers Following Weightlifting Exercise Pomegranate Supplementation Accelerates Recovery of Muscle Damage and Soreness and Inflammatory Markers after a Weightlifting Training Session The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. Isoflavones and cognitive function in older women: the SOy and Postmenopausal Health In Aging (SOPHIA) Study An examination of the efficacy of Ginkgo biloba extract EGb761 on the neuropsychologic functioning of cognitively intact older adults. Reliability of the PEDro scale for rating quality of randomized controlled trials. The effects of dietary supplementation with isoflavones from red clover on cognitive function in postmenopausal women Flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in healthy humans The course of cognitive impairment in preclinical Alzheimer disease: three- and 6-year follow-up of a population-based sample. A Randomized, Double-Blinded, Placebo-Controlled Study to Compare the Safety and Efficacy of Low Dose Enhanced Wild Blueberry Powder and Wild Blueberry Extract (ThinkBlue™) in Maintenance of Episodic and Working Memory in Older Adults Polyphenols From Grape and Blueberry Improve Episodic Memory in Healthy Elderly with Lower Level of Memory Performance: A Bicentric Double-Blind, Randomized, Placebo-Controlled Clinical Study. The Acute and Chronic Cognitive and Cerebral Blood Flow Effects of a Sideritis scardica (Greek Mountain Tea) Extract: A Double Blind, Randomized, Placebo Controlled, Parallel Groups Study in Healthy Humans Multidomain Interventions to Prevent Cognitive Impairment, Alzheimer’s Disease, and Dementia: From FINGER to World-Wide FINGERS Enhanced task-related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation. Dietary flavonols and risk of Alzheimer dementia
BACKGROUND a small number of reports exist on the cognitive effects of soy isoflavones , the findings from which are mixed . Isoflavone efficacy is dependent upon conversion of glycosides contained in soy foods and supplements to the biologically active aglycons . Of particular interest is the production of the metabolite , equol , which is dependent upon intestinal microflora and an integrous digestive system , both being altered by age and age-associated conditions . Unfortunately , few studies enrolled adults over the age of 70 , and none included older men . OBJECTIVE we examined safety , feasibility and cognitive efficacy of soy isoflavone administration in older nondemented men and women ( age 62 - 89 years ) . DESIGN AND METHODS in this r and omised , placebo-controlled , double-blind pilot study , subjects ingested either 100 mg/day soy isoflavones ( glycoside weight ) or matching placebo tablets for 6 months . RESULTS active and placebo-treated subjects exhibited a comparable side-effect profile . Plasma levels of genistein and daidzein ( P < 0.001 ) , but not equol , increased with isoflavone administration . While similar at baseline , the two groups differed across 6 months of treatment on 8 of 11 cognitive tests administered . Isoflavone-treated subjects improved on tests of visual-spatial memory ( P < 0.01 ) and construction ( P = 0.01 ) , verbal fluency ( P < 0.01 ) and speeded dexterity ( P = 0.04 ) . Placebo-treated participants were faster than isoflavone-treated subjects on two tests of executive function ( P < 0.05 ) . CONCLUSIONS these data suggest that administration of 100 mg/day of isoflavones was well tolerated . Plasma genistein and daidzein levels , but not equol , increased with isoflavone administration . Finally , data support the potential cognitive effects of soy isoflavones in older adults 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 Regular consumption of fruit and vegetables may be associated with decreased CVD risk . In the present study , we investigated the effects of blackcurrant ( BC ) juice , rich in polyphenols and ascorbic acid , on oxidative and inflammatory biomarkers in cultured macrophages in vitro and in human subjects with an atherosclerosis-prone phenotype ( after consumption of a high-energy meal ) . In cultured macrophages ( RAW264.7 ) , BC treatment significantly inhibited lipopolysaccharide-induced inflammation as indicated by lower mRNA levels of TNF-α , IL-1β and inducible NO synthase ( iNOS ) and lower nuclear p65 levels indicating decreased NF-κB activity . iNOS protein levels were lower and haem oxygenase 1 levels higher in BC-treated cells when compared with untreated controls . Subjects given a high-energy meal had elevated serum glucose and insulin levels with no significant difference between the BC-based juice and placebo treatment groups . TAG following meal ingestion tended to be attenuated after the BC treatment . Plasma ascorbic acid and radical-scavenging capacity were decreased following placebo meal consumption ; however , BC significantly elevated both parameters compared with baseline and placebo ingestion . Plasma oxidised LDL , α-tocopherol and paraoxonase activity were unchanged in both treatment groups . Furthermore , production of TNF-α and IL-1β was not significantly changed by BC meal consumption . The present results suggest potential antioxidative and anti-inflammatory properties of BC in vitro in cultured macrophages . Although the observations were not directly transferable to a postpr and ial in vivo situation , the present results show that BC juice consumption may improve postpr and ial antioxidant status as indicated by higher ascorbic acid levels and free radical-scavenging capacity in plasma The aim of this study was to test the hypothesis that pomegranate juice supplementation would blunt acute and delayed oxidative stress responses after a weightlifting training session . Nine elite weightlifters ( 21.0 ± 1 years ) performed two Olympic-Weightlifting sessions after ingesting either the placebo or pomegranate juice supplements .  Venous blood sample s were collected at rest and 3 min and 48 h after each session . Compared to the placebo condition , pomegranate juice supplementation attenuated the increase in malondialdehyde ( −12.5 % ; p < 0.01 ) and enhanced the enzymatic ( + 8.6 % for catalase and + 6.8 % for glutathione peroxidase ; p < 0.05 ) and non-enzymatic ( + 12.6 % for uric acid and + 5.7 % for total bilirubin ; p < 0.01 ) antioxidant responses shortly ( 3 min ) after completion of the training session . Additionally , during the 48 h recovery period , pomegranate juice supplementation accelerated ( p < 0.05 ) the recovery kinetics of the malondialdehyde ( 5.6 % ) and the enzymatic antioxidant defenses compared to the placebo condition ( 9 to 10 % ) . In conclusion , supplementation with pomegranate juice has the potential to attenuate oxidative stress by enhancing antioxidant responses assessed acutely and up to 48 h following an intensive weightlifting training session . Therefore , elite weightlifters might benefit from blunted oxidative stress responses following intensive weightlifting sessions , which could have implication s for recovery between training sessions Purpose The aim of this study was to investigate the effect of natural Pomegranate juice supplementation on performance and acute and delayed responses of muscle soreness and biomarkers of muscle damage after a weightlifting training session . Methods Nine elite weightlifters ( 21±0.5 years ) performed two Olympic-Weightlifting-sessions after either placebo ( PLA ) or natural pomegranate juice ( POMj ) supplementations .  Heart rate , blood pressure and blood sample s ( hematological parameters , muscle damage and C-reactive protein ( CRP ) ) were collected at rest , 3min and 48h after each session . Weightlifting performance , RPE , and DOMS were also assessed after each training session . Results T-test showed higher performance ( + 8.30 % ) and lower RPE values ( -4.37 % ) using POMj supplementation ( p<0.05 ) in comparison with PLA . For the DOMS values , a significant improvement ( 13.4 % ) was shown only for the knee extensors ( p<0.01 ) using the POMj . Compared to PLA condition , POMj attenuated the acute ( i.e. , 3min ) increase of systolic blood pressure ( SBP ) , HR , CK and LDH ( p<0.05 ; -4.46 % , -1.81 % , -8.75 % , -1.64 % , respectively ) and blunted the significant increase of ASAT , PAL and CRP ( p>0.05 ) . Additionally , during the 48h following the training session , POMj improved the recovery kinetic of SBP ( p<0.01 , 7.97 % ) , CK ( p<0.001 , 11.34 % ) , LDH ( p<0.05 , 7.30 % ) and ASAT ( p<0.05 , 6.77 % ) . Indeed , the present study showed that 48h of recovery associated to natural POMj supplementation was sufficient to reach the resting values of the selected muscle damage markers after intensive training session . Conclusion Natural POMj seems to ameliorate the capacity to adhere to an intensive training program . Therefore , elite weightlifters are advised to use natural POMj during intensive training program and competition to accelerate muscle recovery . Trial Registration Clinical Trials.gov Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Objective This study examines the effects of a dietary supplement of isoflavones on cognitive function in postmenopausal women . Design Participants for this 6-month , double-blind , r and omized , placebo-controlled clinical trial were women who were in good health , were postmenopausal at least 2 years , and were not using estrogen replacement therapy . Between July 24 , 2000 , and October 31 , 2000 , 56 women aged 55 to 74 years were r and omized ; 2 in the placebo group and 1 in the active treatment group did not complete the 6-month evaluation , and none withdrew because of adverse effects . Women r and omized to active treatment ( n = 27 ) took two pills per day , each containing 55 mg of soy-extracted isoflavones ( 110 mg total isoflavones per day ; Healthy Woman :  Soy Menopause Supplement , Personal Products Company , McNeil-PPC Inc. , Skillman , NJ , USA ) . Women assigned to placebo ( n = 26 ) took two identical-appearing pills per day containing inert ingredients . Cognitive function tests administered at baseline and follow-up included the following : Trails A and B , category fluency , and logical memory and recall ( a paragraph recall test assessing immediate and delayed verbal memory ) . Results At baseline , all women were cognitively intact ; there were no significant differences by treatment assignment in age , education , depressed mood , or cognitive function ( all P values > 0.10 ) . Compliance was 98 % and 97 % , respectively , in the placebo and treatment groups ; all women took at least 85 % of their pills . The women in the treatment group did consistently better , both as compared with their own baseline scores and as compared with the placebo group responses at 6 months . Comparisons of percentage change in cognitive function between baseline and follow-up showed greater improvement in category fluency for women on active treatment as compared with the case of those on placebo ( P = 0.02 ) and showed ( nonsignificantly ) greater improvement on the two other tests of verbal memory and Trails B. Conclusion These results suggest that isoflavone supplementation has a favorable effect on cognitive function , particularly verbal memory , in postmenopausal women OBJECTIVES Few investigations have examined the effectiveness of Ginkgo biloba extract for enhancing cognitive abilities in individuals with no history of significant neurocognitive dysfunction . The purpose of this research was to examine the relatively short-term ( i.e. , 6 weeks ) efficacy of Ginkgo biloba extract EGb 761 on the cognitive functioning of cognitively intact persons over the age of 55 years via a diverse battery of neuropsychologic tests and measures . PARTICIPANTS From the 48 cognitively intact participants between the ages of 55 and 86 years who initially enrolled in this study , 21 males and 19 females successfully completed the study 's protocol and provided valid data sets . DESIGN A 6-week , double-blind , fixed-dose , placebo-controlled , parallel-group experimental design was utilized . Participants were r and omly assigned to either a Ginkgo biloba extract EGb 761 ( 180 mg/d ) or placebo control group . To evaluate participants ' cognitive and behavioral functioning , series of neuropsychological tests were administered to them prior to the initiation of the Ginkgo biloba extract/placebo therapy ( i.e. , pretreatment baseline ) and again , just prior to the termination of the treatment regimen ( i.e. , after 6 weeks ) . RESULTS Participants who received 180 mg of Ginkgo biloba extract EGb 761 daily for 6 weeks exhibited significantly more improvement on a task assessing speed of processing abilities ( i.e. , Stroop Color and Word Test color-naming task ) by the end of treatment as compared to participants who received placebo . Trends favoring improved performances in the Ginkgo biloba group were also demonstrated in three of the four remaining tasks that involved a timed , speed of processing component , although they did not reach statistical significance . Furthermore , a significant relationship was found between the type of treatment ( Ginkgo biloba extract or placebo ) and participants ' ratings of their overall abilities to remember . Specifically , more participants in the Ginkgo biloba extract group rated their overall abilities to remember by the end of treatment as " improved , " as compared to the placebo group . In contrast , no significant differences were found between the Ginkgo biloba and placebo groups by treatment end on any of the four objective memory measures . CONCLUSIONS Taken together , the findings from st and ardized neuropsychologic assessment and a subjective , self-report question naire suggested that relatively short-term ( i.e. , 6 weeks ) utilization of Ginkgo biloba extract EGb 761 may prove efficacious in enhancing certain neurocognitive functions/processes of cognitively intact older adults BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . Objective To examine the effects of dietary isoflavone supplementation with an extract from red clover on cognitive function in postmenopausal women . Design Thirty postmenopausal women aged greater than 60 years received either two tablets of an extract of aglycone isoflavones from red clover ( each containing formononetin 25 mg , biochanin 2.5 mg and less than 1 mg of daidzein and genistein ) for 6 months in a r and omized , controlled clinical trial . Cognitive function tests were performed at baseline and at the end of isoflavone or placebo therapy . Results Isoflavone supplementation was associated with an apparent improvement in block design ( a test of visual-spatial intelligence ) compared to placebo ( isoflavone + 12 % , placebo −3 % ; p = 0.03 ) , no improvement in verbal memory compared to an improvement on placebo ( isoflavone + 1 % , placebo + 29 % ; p = 0.023 ) and a deterioration in digit recall compared to placebo ( isoflavone −6 % , placebo + 12 % ; p = 0.029 ) . However , these findings were not statistically significant when corrections were made for potential chance findings due to multiple comparisons . Conclusion Isoflavone supplementation does not appear to have major short-term effects on cognitive function in postmenopausal women . However , further clinical trials are required to determine whether small effects or long-term effects on cognitive function occur during isoflavone supplementation Background Consumption of flavonoid-rich beverages , including tea and red wine , has been associated with a reduction in coronary events , but the physiological mechanism remains obscure . Cocoa can contain extraordinary concentrations of flavanols , a flavonoid subclass shown to activate nitric oxide synthase in vitro . Objective To test the hypothesis that flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in humans . Design The study prospect ively assessed the effects of Flavanol-rich cocoa , using both time and beverage controls . Participants were blinded to intervention ; the endpoint was objective and blinded . Methods Pulse wave amplitude was measured on the finger in 27 healthy people with a volume-sensitive vali date d calibrated plethysmograph , before and after 5 days of consumption of Flavanol-rich cocoa [ 821 mg of flavanols/day , quantitated as (−)-epicatechin , (+)-catechin , and related procyanidin oligomers ] . The specific nitric oxide synthase inhibitor , NG-nitro-l-arginine methyl ester ( l-NAME ) was infused intravenously on day 1 , before cocoa , and on day 5 , after an acute ingestion of cocoa . Results Four days of flavanol-rich cocoa induced consistent and striking peripheral vasodilation ( P = 0.009 ) . On day 5 , pulse wave amplitude exhibited a large additional acute response to cocoa ( P = 0.01 ) . l-NAME completely reversed this vasodilation ( P = 0.004 ) . In addition , intake of flavanol-rich cocoa augmented the vasodilator response to ischemia . Flavanol-poor cocoa induced much smaller responses ( P = 0.005 ) , and none was induced in the time-control study . Flavanol-rich cocoa also amplified the systemic pressor effects of l-NAME ( P = 0.005 ) . Conclusion In healthy humans , flavanol-rich cocoa induced vasodilation via activation of the nitric oxide system , providing a plausible mechanism for the protection that flavanol-rich foods induce against coronary events OBJECTIVES To examine the ability of the  total score  and individual items from the Mini-Mental State Examination in predicting the development of Alzheimer disease ( AD ) across a 3- and 6-year period in a population -based sample , and to describe the longitudinal changes in these measures across the same follow-up periods . DESIGN Prospect i ve follow-up of a community-based cohort , with 3 times of testing across a 6-year period . At each time of measurement , participants were clinical ly examined by physicians to identify demented and nondemented participants according to Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition , criteria . PARTICIPANTS The study population consisted of all participants who were nondemented at the first follow-up and participated in the second follow-up examination . Among those , 459 remained nondemented and 73 developed AD during the second follow-up period . RESULTS Baseline differences in the total Mini-Mental State Examination score and the delayed memory item were seen 6 years before eventual dementia diagnosis ( P<.01 ) . Analysis of the longitudinal changes showed no differences in the rate of decline for the incident AD or nondemented group between time 1 and time 2 ( P>.10 ) . However , the incident AD group exhibited precipitous declines in 8 of the 10 subscales between time 2 and time 3 , the point at which they were clinical ly diagnosed ( P<.01 ) . Logistic regression analyses showed that only the delayed memory item was a significant predictor of who would develop AD , independent of age , sex , and years of education , at both of the first 2 times of measurement ( P<.001 ) . CONCLUSIONS The diagnosis of AD is preceded by a long pre clinical phase in which deficits in memory performance are most common . These deficits remain relatively stable up until the time that a dementia diagnosis can be rendered . Arch Neurol . 2000 Previous research has shown beneficial effects of polyphenol-rich diets in ameliorating cognitive decline in aging adults . Here , using a r and omized , double blinded , placebo-controlled chronic intervention , we investigated the effect of two proprietary blueberry formulations on cognitive performance in older adults ; a whole wild blueberry powder at 500 mg ( WBP500 ) and 1000 mg ( WBP1000 ) and a purified extract at 100 mg ( WBE111 ) . One hundred and twenty-two older adults ( 65–80 years ) were r and omly allocated to a 6-month , daily regimen of either placebo or one of the three interventions .  Participants were tested at baseline , 3 , and 6 months on a battery of cognitive tasks targeting episodic memory , working memory and executive function , alongside mood and cardiovascular health parameters . Linear mixed model analysis found intervention to be a significant predictor of delayed word recognition on the Reys Auditory Verbal Learning Task ( RAVLT ) , with simple contrast analysis revealing significantly better performance following WBE111 at 3 months . Similarly , performance on the Corsi Block task was predicted by treatment , with simple contrast analysis revealing a trend for better performance at 3 months following WBE111 . Treatment also significantly predicted systolic blood pressure ( SBP ) with simple contrast analysis revealing lower SBP following intervention with WBE111 in comparison to placebo . These results indicate 3 months intervention with WBE111 can facilitate better episodic memory performance in an elderly population and reduce cardiovascular risk factors over 6 months Polyphenols are promising nutritional bioactives exhibiting beneficial effect on  age-related cognitive decline .  This study evaluated the effect of a polyphenol-rich extract from grape and blueberry ( PEGB ) on memory of healthy elderly subjects ( 60 - 70 years-old ) . A bicentric , r and omized , double-blind , placebo-controlled trial was conducted with 215 volunteers receiving 600 mg/day of PEGB ( containing 258 mg flavonoids ) or a placebo for 6 months . The primary outcome was the CANTAB Paired Associate Learning ( PAL ) , a visuospatial learning and episodic memory test . Secondary outcomes included verbal episodic and recognition memory ( VRM ) and working memory ( SSP ) . There was no significant effect of PEGB on the PAL on the whole cohort . Yet , PEGB supplementation improved VRM-free recall . Stratifying the cohort in quartiles based on PAL at baseline revealed a subgroup with  advanced cognitive decline ( decliners ) who responded positively to the PEGB . In this group , PEGB consumption was also associated with a better VRM-delayed recognition . In addition to a lower polyphenol consumption , the urine metabolomic profile of decliners revealed that they excreted more metabolites . Urinary concentrations of specific flavan-3-ols metabolites were associated , at the end of the intervention , with the memory improvements . Our study demonstrates that PEGB improves age-related episodic memory decline in individuals with the highest cognitive impairments Background : The presence of polyphenols such as hydroxy-cinnamic acids and flavonoids in Sideritis scardica ( Greek mountain tea )  are likely responsible for the cognitive and mood effects of its consumption and this could be underpinned by the ability of such polyphenols to prevent monoamine neurotransmitter reuptake and to increase cerebral blood flow ( CBF ) . Objective : The current study extends the small amount of Sideritis scardica literature in humans by assessing both cognitive and mood outcomes in a sample of older adults , as well as blood pressure ( BP ) and CBF  , in a sub sample , utilizing near-infrared  spectroscopy ( NIRS ) . Design : This r and omized , double-blind , placebo-controlled , parallel groups trial r and omized N = 155 , 50–70-year-old male and female participants who were assessed for the cognitive ( N = 140 ) , mood ( N = 142 ) , BP ( N = 133 ) and CBF ( N = 57 ) effects of two doses of Greek mountain tea ( 475 and 950 mg ) as well as an active control of 240 mg Ginkgo biloba , and a placebo control , following acute consumption ( Day 1 ) and following a month-long consumption period ( Day 28 ) . Results : Relative to the placebo control , 950 mg Greek mountain tea evinced significantly fewer false alarms on the Rapid Visual Information Processing ( RVIP ) task on Day 28 and significantly reduced state anxiety following 28 days consumption ( relative also to the active , Ginkgo control ) . This higher dose of Greek mountain tea also attenuated a reduction in accuracy on the picture recognition task , on Day 1 and Day 28 , relative to Ginkgo and both doses of Greek mountain tea trended towards significantly faster speed of attention on both days , relative to Ginkgo . Both doses of Greek mountain tea , relative to placebo , increased oxygenated haemoglobin ( HbO ) and oxygen saturation ( Ox% ) in the prefrontal cortex during completion of cognitively dem and ing tasks on Day 1 . The higher dose also evinced greater levels of total ( THb ) and deoxygenated ( Hb ) haemoglobin on Day 1 but no additional effects were seen on CBF on Day 28 following either dose of Greek mountain tea . Ginkgo biloba led to lower levels of Ox% and higher levels of Hb on Day 1 and lower levels of both HbO and THb on Day 28 . Conclusions : The significantly improved cognitive performance following Greek mountain tea on Day 1 could be due to significant modulation of the CBF response . However , these improvements on Day 28 are more likely to be due to the reductions in state anxiety and , taken together , suggests that the former mechanism is more likely to facilitate acute cognitive effects and the latter more likely to underpin more prolonged cognitive improvements Alzheimer ’s disease ( AD ) and dementia are a global public health priority , and prevention has been highlighted as a pivotal component in managing the dementia epidemic . Modifiable risk factors of dementia and AD include lifestyle-related factors , vascular and metabolic disorders , and psychosocial factors . R and omized controlled clinical trials ( RCTs ) are needed to clarify whether modifying such factors can prevent or postpone cognitive impairment  and dementia in older adults . Given the complex , multifactorial , and heterogeneous nature of late-onset AD and dementia , interventions targeting several risk factors and mechanisms simultaneously may be required for optimal preventive effects . The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability ( FINGER ) is the first large , long-term RCT to demonstrate that a multidomain lifestyle-based intervention ameliorating vascular and lifestyle-related risk factors can preserve cognitive functioning and reduce the risk of cognitive decline among older adults at increased risk of dementia . To investigate the multidomain intervention in other population s and diverse cultural and geographical setting s , the World-Wide FINGERS ( WW-FINGERS ) network was recently launched ( https://alz.org/wwfingers ) . Within this network , new FINGER-type trials with shared core methodology , but local culture and context -specific adaptations , will be conducted in several countries . The WW-FINGERS initiative facilitates international collaborations , provides a platform for testing multidomain strategies to prevent cognitive impairment and dementia , and aims at generating high- quality scientific evidence to support public health and clinical decision-making . Furthermore , the WW-FINGERS network can support the implementation of preventive strategies and translation of research findings into practice Blueberries are rich in flavonoids , which possess antioxidant and anti-inflammatory properties . High flavonoid intakes attenuate age-related cognitive decline , but data from human intervention studies are sparse . We investigated whether 12 weeks of blueberry concentrate supplementation improved brain perfusion , task-related activation , and cognitive function in healthy older adults . Participants were r and omised to consume either 30 mL blueberry concentrate providing 387 mg anthocyanidins ( 5 female , 7 male ; age 67.5 ± 3.0 y ; body mass index , 25.9 ± 3.3 kg·m-2 ) or isoenergetic placebo ( 8 female , 6 male ; age 69.0 ± 3.3 y ; body mass index , 27.1 ± 4.0 kg·m-2 ) . Pre- and postsupplementation , participants undertook a battery of cognitive function tests and a numerical Stroop test within a 1.5 T magnetic resonance imaging scanner while functional magnetic resonance images were continuously acquired . Quantitative resting brain perfusion was determined using an arterial spin labelling technique , and blood biomarkers of inflammation and oxidative stress were measured . Significant increases in brain activity were observed in response to blueberry supplementation relative to the placebo group within Brodmann areas 4/6/10/21/40/44/45 , precuneus , anterior cingulate , and insula/thalamus ( p < 0.001 ) as well as significant improvements in grey matter perfusion in the parietal ( 5.0 ± 1.8 vs -2.9 ± 2.4 % , p = 0.013 ) and occipital ( 8.0 ± 2.6 vs -0.7 ± 3.2 % , p = 0.031 ) lobes . There was also evidence suggesting improvement in working memory ( 2-back test ) after blueberry versus placebo supplementation ( p = 0.05 ) . Supplementation with an anthocyanin-rich blueberry concentrate  improved brain perfusion and activation in brain areas associated with cognitive function in healthy older adults Objective To determine whether dietary intake of flavonols is associated with Alzheimer dementia . Methods The study was conducted among 921 participants of the Rush Memory and Aging Project ( MAP ) , an ongoing community-based , prospect i ve cohort . Participants completed annual neurologic evaluations and dietary assessment s using a vali date d food frequency question naire . Results Among 921 MAP participants who initially had no dementia in the analyzed sample , 220 developed Alzheimer dementia . The mean age of the sample was 81.2 years ( SD 7.2 ) , with the majority ( n = 691 , 75 % ) being female . Participants with the highest intake of total flavonols had higher levels of education and more participation in physical and cognitive activities . In Cox proportional hazards models , dietary intakes of flavonols were inversely associated with incident Alzheimer dementia in models adjusted for age , sex , education , APOE ɛ4 , and participation in cognitive and physical activities . Hazard ratios ( HRs ) for the fifth vs first quintiles of intake were as follows : for total flavonol , 0.52 ( 95 % confidence interval [ CI ] , 0.33–0.84 ) ; for kaempferol , 0.49 ( 95 % CI , 0.31–0.77 ) ; for myricetin , 0.62 ( 95 % CI , 0.4–0.97 ) ; and for isorhamnetin , 0.62 ( 95 % CI , 0.39–0.98 ) . Quercetin was not associated with Alzheimer dementia ( HR , 0.69 ; 95 % CI , 0.43–1.09 ) . Conclusion Higher dietary intakes of flavonols may be associated with reduced risk of developing Alzheimer dementia
CONTEXT As the food industry is continually involved in the development of new attractive alternative therapeutic agents , the evaluation of the beneficial impact of (poly)phenols on cognitive and brain function during aging has gained increasing interest .
OBJECTIVE This systematic review and meta- analysis aim ed to evaluate the acute and chronic effects of (poly)phenol-rich diet supplementation on  cognitive function and brain health in aging adults .