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Brickman AM, Khan UA, Provenzano FA, Yeung LK, Suzuki W, Schroeter H, Wall M, Sloan RP, Small SA. 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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UCLA/VA
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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