Fig 2 - available from: European Journal of Nutrition
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a Mean word recognition accuracy (± Standard error of the mean) at all-time points following WBB or control intervention. Placebo accuracy can be seen to significantly decrease between baseline and 120 min, 360 min, and 480 min whereas no such decrease is found for WBB. b Mean word rejection accuracy (± Standard error of the mean) at all-time points following WBB or control intervention. Placebo accuracy can be seen to significantly decrease between baseline and 240 min, and baseline and 480 min. WBB accuracy can be seen to significantly decrease between baseline and 360 min and 240 min and 360 min
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PurposeResearch has demonstrated cognitive benefits following acute polyphenol-rich berry consumption in children and young adults. Berry intake also has been associated with metabolic benefits. No study has yet examined cognitive performance in middle-aged adults. We investigated the relationships among cognitive and metabolic outcomes in middle-a...
Citations
... Considering known metabolite peaks, the 5 h time point may have been too early to detect cognitive change. Other work from our laboratory has shown that the cognitive effects of blueberry treatment in children [15][16][17][18] and middle-aged adults [19] coincide with polyphenol metabolite peaks in plasma between 1-2 h and 6 h post consumption, highlighting these as potentially sensitive windows for physiological and cognitive change. It would also be reasonable to expect the amplitude of these peaks to be increased by stabilisation of anthocyanins in WBE. ...
... Circadian fluctuations in sustained attention are generally less pronounced in older adults compared with young adults, and the amplitude of circadian changes in attention is much lower for the more difficult aspects of a task [27]. These findings are interesting when combined with previous results that have identified flavonoid sensitivity under conditions of high cognitive demand [16,17,19,28,29]. Additionally, berry treatments have shown to be effective at alleviating the natural temporal decline in cognition across the course of a day in children [16], young adults [28], and middle-aged adults [29]. ...
... This aligns with previous research across child [16], young adult [28], and middleaged adult [19] populations, where berry treatments alleviated the natural decline in cognition across the course of a day. Further support for a postprandial cognitive dip was evidence by a reduction in episodic memory at the 4 h timepoint. ...
Background: Circadian and homeostatic declines in cognitive performance are observed during the day, most commonly at 14:00. Additionally, postprandial reductions in cognitive ability have been widely demonstrated 1 h after lunch consumption, affecting domains of executive functioning (EF), episodic memory (EM), and attention. Existing evidence shows that anthocyanin-rich foods such as berries may improve or attenuate the decline in EF and EM in ageing adults. Further research is required to assess whether extracts such as wild blueberry extract (WBE) may be beneficial for cognitive function across an acute timeframe, including known periods of reduced functioning. Objectives: (1) Study 1: ROAB: To investigate the efficacy of WBE in maintaining EF and EM throughout the day alongside measures of cardiovascular outcomes in healthy older adults. A range of WBE doses were utilised to identify the optimal dose at which cognitive and cardiovascular effects occur. (2) Study 2: BEAT: To replicate alleviation of cognitive decline during a predicted post-lunch dip whilst also improving cardiovascular outcomes following acute WBE 222 mg supplementation. Methods: Both studies employed a randomised, double-blind, cross-over, placebo-controlled design to explore the effects of WBE intervention versus placebo on several outcomes, including EM, EF, blood pressure, and heart rate in a healthy older adult population (aged 68–75). In ROAB, 28 participants received a single dose of WBE 111 mg, 222 mg, 444 mg, or 888 mg or placebo over a 5-week period, each separated by a 1-week washout. Outcomes were measured at 0 h, 2 h, 4 h, and 6 h post intervention, with intervention occurring immediately after baseline (0 h). In BEAT, 45 participants received WBE 222 mg and placebo (1-week washout). Outcomes were measured at 0 h and 6 h (14:00) when a post-lunch dip was anticipated. This was further enhanced by consumption of lunch 1 h prior to cognitive testing. The WBE 222 mg intervention aligned with known peaks in plasma blueberry polyphenol metabolites at 2 h post dosing, which would coincide with a predicted drop in post-lunch performance. Results: ROAB: A significant dip in executive function was apparent at the 4 h timepoint for placebo only, indicating attenuation for WBE doses. Strikingly, WBE 222 mg produced acute reductions in both systolic and diastolic blood pressure compared with placebo. BEAT: EF reaction time was found to be significantly faster for WBE 222 compared to placebo at the predicted post-lunch dip (14:00), with no other notable benefits on a range of cognitive and cardiovascular outcomes. Conclusion: These two studies indicate that WBE may have cardiovascular benefits and attenuate the natural cognitive decline observed over the course of the day, particularly when a decline is associated with a circadian rhythm-driven postprandial dip. However, it is important to acknowledge that effects were subtle, and benefits were only observed on a small number of outcomes. Further research is required to explore the utility of WBE in populations already experiencing mild cognitive impairments.
... Drug development for neurodegenerative diseases is evolving towards targeting pathways relevant to both aging and neurodegeneration, and oxytosis/ferroptosis has been hypothesized to be involved in the pathophysiology of age-related neurodegenerative diseases [9,10,46]. Flavonoids have been proven to be neuroprotective compounds with a potential for slowing neurodegenerative diseases demonstrated by clinical evidence [47][48][49][50][51]. These compounds exhibit multi-target activity and numerous properties such as the modulation of the blood-brain barrier permeability, direct and indirect antioxidant activity, and anti-amyloidogenic and anti-inflammatory properties, making them a valuable source of drug candidates amongst natural products [15,52]. ...
The global increase in the aging population has led to a rise in many age-related diseases with continuing unmet therapeutic needs. Research into the molecular mechanisms underlying both aging and neurodegeneration has identified promising therapeutic targets, such as the oxytosis/ferroptosis cell death pathway, in which mitochondrial dysfunction plays a critical role. This study focused on sterubin and fisetin, two flavonoids from the natural pharmacopeia previously identified as strong inhibitors of the oxytosis/ferroptosis pathway. Here, we investigated the effects of the compounds on the mitochondrial physiology in HT22 hippocampal nerve cells under oxytotic/ferroptotic stress. We show that the compounds can restore mitochondrial homeostasis at the level of redox regulation, calcium uptake, biogenesis, fusion/fission dynamics, and modulation of respiration, leading to the enhancement of bioenergetic efficiency. However, mitochondria are not required for the neuroprotective effects of sterubin and fisetin, highlighting their diverse homeostatic impacts. Sterubin and fisetin, thus, provide opportunities to expand drug development strategies for anti-oxytotic/ferroptotic agents and offer new perspectives on the intricate interplay between mitochondrial function, cellular stress, and the pathophysiology of aging and age-related neurodegenerative disorders.
... The data extracted from each primary study in the sample are shown in Table 2. The 24 studies in Table 2 comprise 14 reported findings from both immediate and delayed retrieval tasks, with five additional studies that reported relevant findings for immediate retrieval [19,20,23,42,51] and five additional studies that reported relevant findings for only delayed retrieval [52,[55][56][57]64]. Table 1 shows that five of the 24 studies reported findings concerning the acute effects of a single dosage up to 8 h after administration [19,41,47,49,52], with the remaining 19 studies reporting findings concerning chronic administration for up to 2.5 years in one case. ...
... The 24 studies in Table 2 comprise 14 reported findings from both immediate and delayed retrieval tasks, with five additional studies that reported relevant findings for immediate retrieval [19,20,23,42,51] and five additional studies that reported relevant findings for only delayed retrieval [52,[55][56][57]64]. Table 1 shows that five of the 24 studies reported findings concerning the acute effects of a single dosage up to 8 h after administration [19,41,47,49,52], with the remaining 19 studies reporting findings concerning chronic administration for up to 2.5 years in one case. ...
... Forest plot and supporting details for the level one delayed-retrieval meta-analysis. Data is from the following references [21,24,41,43,49,[52][53][54][55][56][57][58][60][61][62]64]. ...
Negative health consequences of obesity include impaired neuronal functioning and cell death, thus bringing the risk of impaired cognitive functioning. Antioxidant properties of polyphe-nols offer a possible intervention for overweight people, but evidence for their effectiveness in supporting cognitive functioning is mixed. This review examined evidence from randomized controlled trials concerning the effect of polyphenols on tasks requiring either immediate or delayed retrieval of learned information, respectively, thus controlling for differences in cognitive processes and related neural substrates supporting respective task demands. Searches of the PubMed/Medline, PsycInfo, and Scopus databases identified 24 relevant primary studies with N = 2336 participants having a BMI ≥ 25.0 kg/m 2. The participants' mean age for the 24 studies exceeded 60 years. Respective meta-analyses produced a significant summary effect for immediate retrieval but not for delayed retrieval. The present findings support a potential positive effect of chronic supplementation with polyphenols, most notably flavonoids, on immediate retrieval in participants aged over 60 years with obesity being a risk factor for cognitive impairment. We recommend further investigation of this potential positive effect in participants with such risk factors. Future research on all populations should report the phenolic content of the supplementation administered and be specific regarding the cognitive processes tested.
... Although verbal learning appears enhanced following short-chronic blueberry intake in healthy populations (i.e., 3mo [29][30][31]), these effects have not been sustained at 6 mo [31], and domains, including reaction times, episodic memory, working memory, spatial memory, and executive function have been unaffected by blueberry intake [30][31][32][33]. To date, only studies in healthy adults (i.e., without elevated cardiometabolic risk profiles) have assessed postprandial cognitive responses to blueberries, with cognitive benefits only attained during demanding and sustained tasks across this limited dataset [34,35]. Interestingly, blueberries have previously improved positive affect measures on the self-reported Positive and Negative Affect Schedule, suggesting mood improvement [36]; yet, this requires confirmation as other studies have not supported this effect [37]. ...
... To date, only studies in healthy adults (i.e., those without elevated cardiometabolic risk profiles, such as MetS) have assessed postprandial cognitive responses to blueberries, with cognitive benefits only attained during demanding and sustained tasks across this limited dataset [34,35]. As identified previously, our cognitive battery was relatively short (at 25 min) and may not have elicited the cognitive load required to observe effects. ...
... A further limitation was that our study was powered to detect a change in the primary end point, chronic insulin resistance (as previously described [18]), and cognitive function, mood, and sleep were secondary outcomes that were not formally powered. Despite this, our chronic intervention groups (i.e., n ¼ 37-39/group) were larger than other blueberry studies that were powered explicitly for cognitive function (i.e., [25][26][27][29][30][31]), and we had similar numbers to comparable postprandial studies (e.g., [34,61]). These descriptive comparisons are supported by our retrospective analysis of statistical power [using G*Power (chronic data) and GLIMMPSE (postprandial data) software], which identified relatively high power for key variables in our chronic (i.e., 95% power for executive function) and postprandial assessments (i.e., 69% power for calmness). ...
Background
Anthocyanin and blueberry intakes positively associated with cognitive function in population-based studies and cognitive benefits in randomized controlled trials of adults with self-perceived or clinical cognitive dysfunction. To date, adults with metabolic syndrome (MetS) but without cognitive dysfunction are understudied.
Objectives
Cognitive function, mood, alertness, and sleep quality were assessed as secondary end points in MetS participants, postprandially (>24 h) and following 6-mo blueberry intake.
Methods
A double-blind, randomized controlled trial was conducted, assessing the primary effect of consuming freeze-dried blueberry powder, compared against an isocaloric placebo, on cardiometabolic health >6 mo and a 24 h postprandial period (at baseline). In this secondary analysis of the main study, data from those completing mood, alertness, cognition, and sleep assessments are presented (i.e., n = 115 in the 6 mo study, n = 33 in the postprandial study), using the following: 1) Bond-Lader self-rated scores, 2) electronic cognitive battery (i.e., testing attention, working memory, episodic memory, speed of memory retrieval, executive function, and picture recognition), and 3) the Leeds Sleep Evaluation Questionnaire. Urinary and serum anthocyanin metabolites were quantified, and apolipoprotein E genotype status was determined.
Results
Postprandial self-rated calmness significantly improved after 1 cup of blueberries (P = 0.01; q = 0.04; with an 11.6% improvement compared with baseline between 0 and 24 h for the 1 cup group), but all other mood, sleep, and cognitive function parameters were unaffected after postprandial and 6-mo blueberries. Across the ½ and 1 cup groups, microbial metabolites of anthocyanins and chlorogenic acid (i.e., hydroxycinnamic acids, benzoic acids, phenylalanine derivatives, and hippuric acids) and catechin were associated with favorable chronic and postprandial memory, attention, executive function, and calmness.
Conclusions
Although self-rated calmness improved postprandially, and significant cognition-metabolite associations were identified, our data did not support strong cognitive, mood, alertness, or sleep quality improvements in MetS participants after blueberry intervention.
This trial was registered at clinicaltrials.gov as NCT02035592.
... Therefore, it is suggested that MoCA is more sensitive to determining the change in ALFF value and early cognitive decline. Also, AVLT is often used to assess memory, an important domain of cognitive function (55,56). In our study, the scores of AVLT-N1, AVLT-N2, and AVLT-N3, reflecting short-term memory, and the scores of AVLT-N5, reflecting delayed recall, were sensitive to ALFF changes. ...
Background
Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are neurodegenerative processing stages of Alzheimer’s disease (AD). Cognitive decline is thought to manifest in intrinsic brain activity changes, but research results yielded conflicting and few studies have explored the roles of brain regions in cognitive decline, and sensitivity of the cognitive field to changes in the altered intrinsic brain activity.
Methods
In this cross-sectional study, 158 elderly participants were recruited from the memory clinic of the First Affiliated Hospital of Nanjing Medical University from July 2019 to May 2021, and grouped into SCD (n=73), MCI (n=46), and normal controls (NC) (n=39). The amplitude of low-frequency fluctuation (ALFF) was calculated and evaluated among the groups. Then canonical correlation analysis (CCA) was conducted to investigate the associations between imaging outcomes and cognitive behaviors.
Results
Neuropsychological tests in different cognitive dimensions and ALFF values of the prefrontal, parietal, and temporal gyrus, were significantly different (P<0.05) among the three groups, with no appreciable decline in daily activity. The changes in intrinsic activities were closely related to the decline in cognitive function (R=0.73, P=0.002). ALFF values in the left middle occipital gyrus, right middle frontal gyrus, left superior frontal gyrus, left angular gyrus, and superior temporal gyrus played significant roles in the analysis, while the Montreal Cognitive Assessment (MoCA) and Auditory-Verbal Learning Test scores were found to be more sensitive to changes in ALFF values.
Conclusions
Spontaneous brain activity is a stable imaging biomarker of cognitive impairment. ALFF changes of the prefrontal, occipital, left angular, and temporal gyrus were sensitive to identifying cognitive decline, and the scores of the Auditory-Verbal Learning Test and MoCA could predict the abnormal intrinsic activities.
... These colorful fruits have gained increasing attention for their health merits and lately their beneficial effects on brain function (13-16). Several different types of berries have been associated with improved cognitive performance, including commonly consumed berries like American highbush blueberries (Vaccinium ashei, Vaccinium virgatum, or Vaccinium corymbosum) (17)(18)(19)(20), lowbush wild blueberries (Vaccinium angustifolium) (21)(22)(23), raspberries (24), strawberries (25, 26), and red grapes (27)(28)(29), etc. There is high variation amongst different types of berries in the quantity and composition of compounds belonging to different polyphenolic classes, as well as other nutrients such as fiber. ...
Our diets greatly influence our health. Multiple lines of research highlight the beneficial properties of eating berries and fruits. In this study, a berry mixture of Nordic berries previously identified as having the potential to improve memory was supplemented to young C57Bl/6J male mice to investigate effects on cognition function, metabolic health, markers of neuroinflammation, and gut microbiota composition. C57Bl/6J male mice at the age of 8 weeks were given standard chow, a high-fat diet (HF, 60%E fat), or a high-fat diet supplemented with freeze-dried powder (20% dwb) of a mixture of Nordic berries and red grape juice (HF + Berry) for 18 weeks (n = 12 animals/diet group). The results show that supplementation with the berry mixture may have beneficial effects on spatial memory, as seen by enhanced performance in the T–maze and Barnes maze compared to the mice receiving the high-fat diet without berries. Additionally, berry intake may aid in counteracting high-fat diet induced weight gain and could influence neuroinflammatory status as suggested by the increased levels of the inflammation modifying IL-10 cytokine in hippocampal extracts from berry supplemented mice. Furthermore, the 4.5-month feeding with diet containing berries resulted in significant changes in cecal microbiota composition. Analysis of cecal bacterial 16S rRNA revealed that the chow group had significantly higher microbial diversity, as measured by the Shannon diversity index and total operational taxonomic unit richness, than the HF group. The HF diet supplemented with berries resulted in a strong trend of higher total OTU richness and significantly increased the relative abundance of Akkermansia muciniphila, which has been linked to protective effects on cognitive decline. In conclusion, the results of this study suggest that intake of a Nordic berry mixture is a valuable strategy for maintaining and improving cognitive function, to be further evaluated in clinical trials.
... Regular consumption of nuts or berries has been reported to support brain health and cognitive function, motor control, mood, and executive function at physiologically relevant intakes [172]. Middle-aged and older adults experienced improvements in balance, gait, and memory, and children experienced higher executive function and positive affect after acute and regular intake of both strawberries and blueberries [32,109,[173][174][175][176]. These beneficial effects may be the result of direct effects on brain signaling or indirect effects through oxidant defense and anti-inflammatory properties of polyphenols and other bioactive compounds in nuts and berry foods [177][178][179]. ...
Consumption of nuts and berries are considered part of a healthy eating pattern. Nuts and berries contain a complex nutrient profile, consisting of essential vitamins and minerals, fiber, polyunsaturated fatty acids, and phenolics in quantities that improve physiological outcomes. The spectrum of health outcomes that may be impacted by the consumptions of nuts and berries include cardiovascular, gut microbiome, and cognitive, among others. Recently, new insights regarding the bioactive compounds found in both nuts and berries have reinforced their role for use in precision nutrition efforts. However, challenges exist that can affect the generalizability of outcomes from clinical studies, including inconsistency in study designs, homogeneity of test populations, variability in test products and control foods, and assessing realistic portion sizes. Future research centered on precision nutrition and multi-omics technologies will yield new insights. These and other topics such as funding streams and perceived risk-of-bias were explored at an international nutrition conference focused on the role of nuts and berries in clinical nutrition. Successes, challenges and future directions with these foods are presented here.
... This relationship has been confirmed in investigations of American, French, and Spanish speakers [21][22][23]. A significant plant consumption has also been linked in several studies to the maintenance of cognition [24][25][26], with the benefit of combined fruit and vegetable intake being more prominent. Despite the paucity of data from Asian cultures, several studies have shown links between fruit and vegetable consumption and cognitive decline [27]. ...
Background:
In view of the rapidly accelerating aging process in China, this study looked at the associations between vegetables and fruits intake pattens and cognitive function among the oldest old in China using the genetic sub study from the Chinese Longitudinal Healthy Longevity Survey (CLHLS).
Methods:
This study screened respondents who participated in all four surveys of longitudinal data from the CLHLS, and a total of 2454 participants were ultimately included. The relationships of cognitive function with vegetables and fruits intake patterns were examined using Generalized-estimating equations.
Results:
The prevalence range of mild cognitive impairment (MCI) was 14.3% to 16.9% at T1 to T3 and 32.7% at T4. There was a significant increase in the prevalence of MCI from T1 to T4 (β = 0.054; 95% CI, 0.037 to 0.070; p < 0.001; adjusted). The V+/F+ pattern significantly improved cognitive function in Chinese older adults compared with the V-/F- pattern (OR, 1.026; 95% CI, 1.001-1.053; p < 0.05).
Conclusion:
Older adults who frequently consume both fruits and vegetables experience a reduction in MCI risk relative to those consuming these food groups infrequently-emphasizing the critical importance of the regular intake of both fruits and vegetables in maintaining cognitive function.
... They are rich in flavones and other phenolic compounds, and can be used as the raw materials for manufacturing functional foods. In recent years, they have attracted much attention for exhibiting a broad array of biological functions, such as antioxidant and anti-inflammatory capabilities, preventive neurodegeneration and cardiovascular disease properties, and the amelioration of vision effects, etc. [4][5][6]. The anthocyanins are the most important group of bioactive compounds in plants, including blueberries and bilberries, and polyphenols of the flavonoid we lay the foundations for DR prevention by using anthocyanins-enriched dietary supplements. ...
The aim of the present study was to determine the major anthocyanins of blueberry extracts from northeast China and explore their vision health improvement effects. HPLC-Q-TOF-MS/MS results suggested that six different anthocyanins were accurately identified, among which the Cy-3-glu (C3G) was the most abundant, ranging from 376.91 ± 7.91 to 763.70 ± 4.99 μM. The blueberry extract contained a higher purity of anthocyanins, and the anthocyanosides reached 342.98 mg/kg. The anti-oxidative stress function of C3G on HG-treated ARPE-19 cells were evaluated, and showed that the GSSG level of HG-cells pretreated with 10 μM C3G was significantly decreased, while the Nrf2 and NQO1 gene expression levels were increased. Further molecular docking (MD) results indicated that the C3G displayed favorable binding affinity towards REDD1, and only the B-ring of the C3G molecule displayed binding interactions with the CYS-140 amino acids within the REDD1 protein. It implied that the oxidative stress amelioration effects of C3G on the ARPE-19 cells were related to the REDD1 protein, which was probably via the Nrf2 pathways, although further studies are needed to provide mechanism evidence. The present study provides novel insights into understanding the roles of blueberry anthocyanins in ameliorating oxidative stress-induced BRB damage in the retina.
... Manipulated the polyphenol content of breakfast(Kennedy et al., 2020;Whyte et al., 2021). Forest plot of the effect of glycaemic load on immediate episodic memory for each postprandial time window. ...
The effect of breakfast glycaemic load (GL) on cognition was systematically examined. Randomised and non-randomised controlled trials were identified using PubMed, Scopus, and Cochrane Library (up to May 2022). 15 studies involving adults (aged 20-80 years) were included. Studies had a low risk, or some concerns, of bias. A random-effects meta-analysis model revealed no effect of GL on cognition up to 119 minutes post-consumption. However, after 120 minutes, immediate episodic memory scores were better following a low-GL compared to a high-GL (SMD = 0.16, 95% confidence interval [CI] =-0.00-0.32, p = 0.05, I2 = 0%). Subgroup analyses indicated that the benefit was greater in younger adults J o u r n a l P r e-p r o o f 2 (<35 years) and those with better GT. A qualitative synthesis of 16 studies involving children and adolescents (aged 5-17 years) suggested that a low-GL breakfast may also benefit episodic memory and attention after 120 minutes. Methodological practises were identified which could explain a failure to detect benefits in some studies. Consequently, guiding principles were developed to optimise future study design. Abbreviations GT = glucose tolerance IGT = impaired glucose tolerance T2DM = type 2 diabetes mellitus GL = glycaemic load LGL = low glycaemic load MGL = medium glycaemic load HGL = high glycaemic load GI = glycaemic index LGI = low glycaemic index HGI = high glycaemic index RCTs = randomised controlled trials BMI = body mass index J o u r n a l P r e-p r o o f 3 SMD = standardised mean difference SD = standard deviation CI = confidence interval PRISMA = Preferred Reporting Items for Systematic reviews and Meta-Analysis WHO = World Health Organisation
