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  1. Here's a recent article: Consumption of anthocyanin-rich cherry juice for 12 weeks improves memory and cognition in older adults with mild-to-moderate dementia. PURPOSE:Dietary flavonoids, including anthocyanins, may positively influence cognition and may be beneficial for the prevention and treatment of dementia. We aimed to assess whether daily consumption of anthocyanin-rich cherry juice changed cognitive function in older adults with dementia. Blood pressure and anti-inflammatory effects were examined as secondary outcomes. METHODS:A 12-week randomised controlled trial assessed cognitive outcomes in older adults (+70 year) with mild-to-moderate dementia (n = 49) after consumption of 200 ml/day of either a cherry juice or a control juice with negligible anthocyanin content. Blood pressure and inflammatory markers (CRP and IL-6) were measured at 6 and 12 weeks. ANCOVA controlling for baseline and RMANOVA assessed change in cognition and blood pressure. RESULTS:Improvements in verbal fluency (p = 0.014), short-term memory (p = 0.014) and long-term memory (p ≤ 0.001) were found in the cherry juice group. A significant reduction in systolic (p = 0.038) blood pressure and a trend for diastolic (p = 0.160) blood pressure reduction was evident in the intervention group. Markers of inflammation (CRP and IL-6) were not altered. CONCLUSION:Inclusion of an anthocyanin-rich beverage may be a practical and feasible way to improve total anthocyanin consumption in older adults with mild-to-moderate dementia, with potential to improve specific cognitive outcomes. For more on cognitive benefits: Berry Anthocyanins (Blackcurrant, Blueberry, Cherry, Cranberry, Grape) "As shown in Table 2, berries contain a range of different flavonoid subclasses, but they are typically richest in anthocyanins. Initial berry studies predominantly investigated the cognitive effects of whole fruit. For example, Dodd [25] demonstrated improved accuracy on a letter memory task (measuring working memory) following freeze dried whole blueberries (200 g fresh equivalent, 631 mg anthocyanidins), in 19 young adults at a postprandial time point of 5 h (d = 0.57). The study employed a double blind, crossover design with an energy matched control condition. No effects were observed at an earlier time of 2 h or for other measures of executive function, memory, or mood. For a subset of participants, blood samples taken 1 h postprandially revealed a trend towards increased plasma levels of brain-derived neurotrophic factor (BDNF) in the blueberry condition. Unfortunately, cognition was not measured at this time point so it is impossible to say whether the neurochemical changes are related to the cognitive outcome. In the same study, older adults’ BDNF values decreased from baseline for both blueberry and placebo conditions, but the decrease at the 1 h time point was attenuated in the blueberry condition. These older adults (n = 18) showed improved performance on an immediate word recognition task at both 2 h (d = 0.44) and 5 h (d = 0.69) postprandially, but no improvements in executive function or mood were observed. A later study by Whyte and Williams [26], using fresh whole blueberries (200 g, 143 mg anthocyanins), investigated cognitive effects in children. They found no effects at 2 h for a range of executive function tasks, but did observe a significant improvement in delayed word recall using the Rey auditory verbal learning task (RAVLT) (d = 0.74). This was a small, crossover study with only 14 participants. As no baseline measures were taken, variations in performance across test days may have reduced the statistical power. Nevertheless, the medium effect size for the RAVLT provides good evidence for positive effects of blueberry flavonoids in children. Whyte, Schafer and Williams [27] conducted a larger (n = 21) double-blind, placebo-controlled, crossover study investigating the cognitive effects of 2 separate blueberry doses (127 mg and 253 mg anthocyanins), again in children. The highest dose resulted in significant improvements in immediate word recall after 1.25 h (d = 0.80), and in delayed word recognition after 6 h (d = 0.78). Improved accuracy was observed during a flanker interference task after 3 h, although only for cognitively demanding incongruent trials (d = 0.78). However, reaction times for a Go-NoGo measure of inhibition revealed significantly faster performance following the placebo compared with the blueberry interventions. The positive blueberry effects in older adults and children appear to be focussed on episodic memory, whereas improvements in executive function are more consistent in young adults. The differences in cognitive domains may be an artefact of the small sample sizes, but could also be indicative of age differences in the capacity for improvement in underlying neuronal structures. For example, hippocampal function may be more receptive during development in childhood and decline in old age, whilst frontal regions associated with executive function may be more sensitive in young adulthood. It is noteworthy that neurochemical changes in BDNF were apparent after 1 h, yet distinct time points for memory effects emerged at 1.25–2 h and 5 h, but not at an intervening 3 h time point. At this stage only BDNF trends have been observed, and not directly in association with cognitive changes. Although it is perhaps premature to comment on the relationship between acute changes in cognition and BDNF, it has nevertheless been posited that flavonoid induced increases in BDNF may facilitate stronger memory encoding [27]. Possible mechanisms of action are discussed below. Overall, the timings of cognitive effects are likely to be related to the digestion, absorption and metabolism of flavonoids, but further mapping of cognitive and physiological observations is required in order to resolve inconsistencies within the current observations. The flavonoid content of blueberries is known to vary widely depending on growing, processing and storage conditions [28,29]. The same 200 g quantity of whole blueberries used in the first two studies [25,26] described above showed extreme differences in flavonoid content (631 mg anthocyanidins and 143 mg anthocyanins respectively). This highlights the importance of analysing fresh fruits for their flavonoid content when conducting an intervention. It is also important to note that compositional analysis of anthocyanins typically (but not exclusively) involves the removal of saccharide conjugates prior to quantification; therefore anthocyanin content is often reported as anthocyanidin equivalent. This difference is critical when comparing doses between studies. For example, a berry intervention reported to contain 100 mg cyanidin may actually contain 156 mg chrysanthemin (a saccharide of cyanidin). Some studies reviewed here appear to use the terms anthocyanins and anthocyanidins interchangeably without acknowledging this distinction, making it unclear whether a reported anthocyanin dose is actually referring to an equivalent anthocyanidin dose. Similarly to blueberries, blackcurrants are a rich source of anthocyanins. Watson et al. [30] conducted a double-blind, controlled crossover trial of two blackcurrant extracts (cold-pressed juice or freeze-dried powder). Improved attention compared with an energy-matched control was observed in 36 young adults during a 70-min-long, cognitively fatiguing battery, beginning 1 h postprandially. Specifically, declining accuracy on a rapid visual information processing (RVIP) task was attenuated after taking the powdered extract (d = 0.10, d = 0.47, d = 0.47, d = 0.49, d = 0.49, d = 0.59, d = 0.56, measured for 7 task repetitions; once every 10 min). Similarly, a slowing of reaction time on a digit vigilance task following both blackcurrant and placebo interventions was attenuated after taking the juiced extract (d = 0.60, d = 0.73 and d = 0.60 for the 1st, 4th and 7th repetitions of the task, respectively). No effects were observed for the Stroop test (a measure of inhibition and attention), or for subjective measures of mood and mental fatigue. The total polyphenol content of the two extracts were matched at 525 mg/60 kg bodyweight. However, the anthocyanin content differed slightly; 483 mg/60 kg bodyweight for the powder and 467 mg/60 kg for the juice. This difference was also reflected in the analysis of plasma anthocyanin levels, which were observed to be higher following consumption of the powdered extract compared with the juice. Interestingly, the juice but not the powder was observed to inhibit platelet monoamine oxidase (MAO) and to attenuate blood glucose decline over the duration of the 70-min task battery. This study suggests that the way an extract is prepared may influence cognitive and physiological outcomes, however as different blackcurrant cultivars were used for each extract, the contrasting observations may simply represent compositional differences such as the ratio of flavonoid subclasses present. For the juiced blackcurrant extract, MAO inhibition and blood glucose regulation emerge as possible mechanisms of action further to the neurochemical changes observed for blueberries. The significant cognitive effects were observed for tests of executive function (RVIP and to some extent vigilance) which is consistent with the executive function benefits reported in healthy young adults following blueberry anthocyanins. In a double-blind crossover intervention study, Hendrickson and Mattes [31] investigated whether an acute dose of grape juice would mitigate deficits in mood and cognition that commonly occur following a large meal. Approximately 600 mL (10 mL/kg), containing around 580 mg anthocyanins, was administered to young adult smokers along with a standardised lunch. Smokers were selected on the rationale that this population have an increased propensity to oxidative stress, and because smoking abstinence can exaggerate the post-meal dip in cognitive or affective state, thus this population may be more sensitive to the effects of flavonoids than healthy non-smokers. This was a large study (n = 35) with considerable statistical power, yet no significant effects of grape juice were observed 1 h postprandially when compared to an energy matched placebo condition. Mood ratings for positive mood states (pleasure, arousal and vigor) were observed to decline under both grape and placebo conditions, similarly ratings of negative mood states (confusion and fatigue) increased under both conditions. Although mood generally declined, word fragment completion task performance did not significantly change over time in either condition. It is unfortunate that performance on only one cognitive domain was examined (implicit memory), which is an area that has not previously been considered with respect to flavonoid intervention. Studies may be more likely to observe effects on traditional measures of explicit memory and executive function. Recently, Caldwell et al. [32] published their investigations into the effects of cherry flavonoids. Following administration of 300 mL cherry juice (55 mg anthocyanins) to younger adults (n = 6), older adults (n = 5) and older adults with mild cognitive impairment (n = 5), tests of executive function, speed of processing, and verbal learning and memory were performed at baseline and 6 h postprandially. At 6 h, the older adults displayed improved task switching performance compared to baseline (db = 0.75). No other cognitive effects were observed. The authors attribute this single effect to type 1 error, citing attrition of participants in that group as a likely cause. However the small sample size in all groups suggests that the whole study is likely to be severely underpowered. The lack of an energy matched, low flavonoid control condition is also cause for concern; a second crossover condition only administered the same juice in three separate 100 mL aliquots each consumed 1 h apart. No cognitive effects were observed relative to baseline following consumption of the juice in these consecutive smaller doses. A further problem may be the intervention itself; the anthocyanin content of the cherry juice appears very low compared to some of the above studies. A considerably larger, controlled study is therefore needed to determine if cherry anthocyanins elicit acute cognitive effects similar to those of other anthocyanin-rich fruits." Anthocyanins are an interesting class of dietary polyphenols with many health benefits including targeting metabolic syndrome and obesity [1]: “Polyphenols are family of polar compounds found in fruits and vegetables, they have been popular for their potent antioxidant effect, but in the past 5 years increasing evidence has shown that, anthocyanins, a specific category of polyphenols, are effective in ameliorating obesity and insulin resistance. The mode of action and pharmacokinetic profile of these compounds is not yet fully elucidated and their bioavailability after oral administration is a matter of continuous controversy. However, there is robust evidence on their efficacy in cardiometabolic problems. Kurimoto et al. reported that anthocyanins from black soy bean increased insulin sensitivity via the activation of AMP-activated protein kinase (AMPK) in skeletal muscle and liver of in type 2 diabetic mice. AMPK, a regulator of glucose and lipid metabolism in liver and muscle cells, is inhibited by olanzapine, which may contribute to the olanzapine-induced hepatic lipid accumulation. Anthocyanins also display insulin-like effects even after intestinal biotransformation. We have previously demonstrated that anthocyanins ameliorate signs of diabetes and metabolic syndrome in obese mice fed with a high fat diet have. Delphinidin 3-sambubioside-5-glucoside (D3S5G), an anthocyanin from Aristotelia chilensis, is as potent as Metformin in decreasing glucose production in liver cells, and it displays insulin-like effect in liver and muscle cells. The anti-diabetic mode of action of anthocyanins have been associated with the transcriptional down-regulation of the enzymes PEPCK and G6P gene in hepatocytes. Prevention of adipogenesis is also another reported mechanmis for some anthocyanins from Aristotelia chilensis. Anthocyanins also induce significant increase in circulating levels of adiponectin in murine models of MetS. This is relevant, since adiponectin is reduced in clozapine-treated patients and weight reduction is associated with higher circulating levels of adiponectin. In a recent study Roopchand et al., demonstrated that blueberry anthocyanins are as potent as metformin in correcting hyperglycemia and obesity in obese hyperglyceminc mice. Dietary anthocyanins have also proven efficacy in decreasing les of the inflammatory mediators PAI-1 and retinol binding protein 4 in obesity and type 2 diabetes . Recent medical and nutritional studies suggest that anthocyanins from diverse dietary sources are potent anti-diabetic, anti-obesity and cardioprotective molecules. Another fact that makes anthocyanins candidates for preventing clozapine-induced lipogenesis is that they are capable of suppressing the inflammatory response through targeting the phospholipase A2, PI3K/Akt and NF-kappaB pathways. These pre-clinical findings were corroborated by clinical evidence showing the dietary anthocyanins from blueberries improve insulin resistance in young obese, non-diabetic adults. The clinical efficacy of polyphenols in SGAs-induced MetS has not yet been established, but a recent pre-clinical demonstrated that, resveratrol, a polyphenol found in grapes, decreases olanzapine-induced weight gain.”