There is a growing body of research from preclinical and adult human trials indicating that both chronic and acute interventions with flavonoids can lead to cognitive improvements (1-4) with berries (the main source of anthocyanins, a particular class of flavonoids, in the human diet) being known to protect against neuronal stress (5) and positively mediate signalling pathways in the brain (6). Indeed, preclinical work has found that 7–12 weeks of supplementation with blueberry anthocyanins produces significant improvements in visuo-spatial memory (7,8).
Similarly, following one-off interventions in adults, improvements have been reported following acute flavonol interventions on memory-related areas such as spatial working memory (9) and attention-related executive function tasks (10), and immediate verbal memory following 12-week supplementation with blueberry and grape anthocyanins (11,12).
The mechanisms by which flavonoids exert these actions on cognitive performance are still being elaborated, including evidence which suggests that they may increase cerebral blood flow (CBF) (13-15) as well as modulate the activation status of neuronal receptors, signalling proteins and gene expression (15). Alternatively, the blueberry-derived flavonoids may act to enhance the efficiency of spatial memory indirectly by acting on the dentate gyrus (DG)-the hippocampal sub-region most sensitive to the effects of ageing (16-18). Blueberry supplementation has been shown to significantly increase the proliferation of precursor cells in the DG (19). This link between DG neurogenesis, cognitive performance and ageing is well documented (20) and may represent another mechanism by which fruits rich in flavonoids may improve memory by acting on the hippocampus.
Blueberry poly¬phenols are also potent intracellular antioxidants even at low concentrations, and their action can be direct or mediated by the enhancement of cell endogenous antioxi¬dants (21). In human beings, blueberry anthocyanins are absorbed unchanged in their glycosylated form and are detectable in serum after their consumption (22,23).
Barros et al., (24) demonstrated an enhancement of long-term memory and an improvement of anxiety-related behaviour (anxiolytic effect) in addition to decreased oxidative damage in the DNA of the hippocampus. An association between berry polyphenol supplementa¬tion and beneficial effects in verbal memory emerged in acute and chronic conditions (25). Furthermore, according to an epidemiological long-scale study performed on older women (26), an increased long-term intake of blueberries is associated with a slower rate of cognitive decline, evaluated through tests on overall cognition and verbal memory; this slowing down is seen to correspond to a delay of aging signs by up to 2.5 years. In elderly subjects with an early age-related memory impairment, a 12-week administration of blueberry juice was shown to improve memory per¬formance, assessed through verbal memory tests relying upon hippocampal function (26). The administration of a formulation of antioxidants including blueberries, was observed to improve processing speed, an aspect of cognition, in elderly adults with no evidence of cognitive impairment (mini-mental state >24) across eight weeks of testing with a good safety profile (27).
A placebo controlled double-blind cross-over study assessed the effect of blueberry powder using repeated tests of verbal memory, word recognition, response interference, response inhibition and levels of processing. Significant blueberry improvements included final immediate recall, delayed word recognition sustained over each period, and accuracy on cognitively demanding incongruent trials in the interference task. Across all measures, cognitive performance improved. The beneficial effects seemed to be particularly sensitive to the cognitive demand of task (28).
Blueberry polyphenols have also been shown to confer a retinal protective activity against light-induced retinal injury in vivo and inhibiting lipid peroxidation of unsaturated fatty acids in the retina was proposed to be another important function to protect the eyes (29). The same authors again demonstrated Blueberry anthocyanins protected against ageing and light-induced damage in retinal pigment epithelial cells (30).
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