. Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults. Nat Neurosci. 2014 Dec;17(12):1798-803. Epub 2014 Oct 26 PubMed.

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  1. In general, this is a very sophisticated and admirable study. Small and colleagues have developed a functional novel-object-recognition test (ModBent) that maps to a dependence on a specific anatomical compartment, the dentate gyrus of the hippocampus. They show that the ModBent correlates with age-related functional declines quantitatively reflected in reduced blood flow that they detected in precise cerebral blood-volume imaging with fMRI. This has permitted a study with small numbers (roughly 10 per group) that still detected significant improvement in ModBent and dentate gyrus (DG) cerebral blood volume with their three-month cocoa-flavanol intervention. The low vs. high flavanol cocoa packets provide a nice placebo-controlled design for this type of intervention. It is also interesting that their aerobic-exercise intervention failed to produce improvements and that their high-flavanol intervention impacted DG but not the entorhinal cortex and related tasks. The ability to distinguish focal improvements will be critical for development of complementary combinations.

    There are a few caveats.

    1) The sample sizes are very small. The improvement in ModBent reaction time (RT) of the high-flavanol group (in supplementary figure 3a) seems as much due to a rise in the low-flavanol group RT at three-month follow-up as to the drop in the high-flavanol group. If the low-flavanol group had been stable, I am not sure that the high-flavanol group would have shown a significant improvement. On this point, it would be helpful if the investigators could tell us whether the low-flavanol group’s baseline RT significantly differed from the high-flavanol group’s RT at three months. The 630-millisecond (ms) improvement of the high-flavanol group compared to low-flavanol over the three-month follow-up appears to drop to a few hundred ms or so if you compare baseline high vs. follow-up high. So while the study needs to be repeated with a larger sample size to be really convincing, at the very least, it provides a new approach for clinical research on brain aging.

    2) The specific improvement in speed in this novel-object task is nice to see in an elegant human study with normal aging subjects, but this type of age-related decline has to be distinguished from the debilitating declines seen with AD. That said, if the effect involves inhibition of neuroinflammation-induced deficits in neurogenesis, or the increased angiogenesis and spine density that some have described in aging rodents, the intervention might become a component of a nutritional program aimed at helping those developing neurodegenerative diseases of aging and associated clinical problems.

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