Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults

Abstract

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 randomized trial, we applied these tools to study healthy 50–69-year-old subjects who consumed either a high or low cocoa–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.

Enhanced task-related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation

“…In the present study, we observed increased task-related brain activation and increased resting-state cerebral perfusion in the parietal and occipital lobes after chronic blueberry supplementation. This seems to provide further support for the concept that the increased task-related brain activation observed by us and others (Bookheimer et al 2013;Krikorian et al 2012;Brickman et al 2014) after chronic polyphenol supplementation can be attributed to improved cerebrovascular function.…”

“…In both cases, the authors attributed this response to improved vascular function, despite the absence of any direct measures of vascular function or perfusion. Similarly, 12 weeks of high flavanol cocoa consumption in a healthy older adult population improved taskrelated activation of the dentate gyrus, which is susceptible to aging-related functional deterioration, as well as performance of cognitive tests that rely upon the contribution of dentate gyrus (Brickman et al 2014). In the present study, we observed increased task-related brain activation and increased resting-state cerebral perfusion in the parietal and occipital lobes after chronic blueberry supplementation.…”

“…Additionally, consumption of high flavanol cocoa (≥900 mg·d −1 ) improved cognitive function in healthy older adults after 8 weeks in comparison to a low flavanol cocoa supplement (Mastroiacovo et al 2015). Brickman et al (2014) found that 12 weeks of high flavanol cocoa consumption enhanced task-related activation of the dentate gyrus and associated cognitive function. Similarly, 4 weeks of supplementation with pomegranate, which are rich in the polyphenols from the elligitannins family, increased task-related brain activation and cognitive function in healthy older adults (Bookheimer et al 2013).…”

A flavanoid component of chocolate quickly reverses an imposed memory deficit

“…While it has been suggested that Epi may enhance cognitive function in humans by increasing cerebral blood flow (van Praag et al, 2007;Brickman et al, 2014), this is unlikely to account for improved memory in Lymnaea as it possesses an open circulatory system. Epi does not remove the stressors; rather, it overcomes the negative effects of the stressors on memory formation.…”

Polyphenols and brain health

“…Similarly, significant increases in regional perfusion across the brain were observed following consumption of a high flavanol drink relative to the low flavanol drink, particularly in the anterior cingulate cortex and the central opercular cortex of the parietal lobe (Lamport et al, 2015). Longer-term interventions (3 months) also with cocoa flavanols in aged subjects revealed increases in cerebral blood volume (fMRI) in the DG of the hippocampus, which was highly correlated with improvements in performance in the DG-dependent Modified Benton task (Brickman et al, 2014). Furthermore, ageing is known to impair vascularisation, endothelial function and decreases endothelial progenitor cell recruitment, which could adversely affect neurogenesis.…”