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

Nature Neuroscience volume 17, pages 17981803 (2014) | Download Citation


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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 flavanol–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.

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Change history

  • 02 November 2014

    In the version of this article initially published online, the abstract referred to a high or low cocoa–containing diet. It should have read high or low cocoa flavanol–containing diet. The error has been corrected for the print, PDF and HTML versions of this article.


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We thank F. Gage for previous discussions and A. Glass for helping with the statistical analysis. This investigation was supported by US National Institutes of Health grants AG034618, AG035015, AG025161 and AG08702, the James S. McDonnell Foundation, and an unrestricted grant by MARS, Inc.

Author information

Author notes

    • Adam M Brickman
    • , Usman A Khan
    •  & Frank A Provenzano

    These authors contributed equally to this work.


  1. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.

    • Adam M Brickman
    • , Usman A Khan
    • , Frank A Provenzano
    • , Lok-Kin Yeung
    •  & Scott A Small
  2. Department of Neurology, Columbia University, New York, New York, USA.

    • Adam M Brickman
    • , Usman A Khan
    • , Frank A Provenzano
    • , Lok-Kin Yeung
    •  & Scott A Small
  3. Center for Neural Science, New York University, New York, New York, USA.

    • Wendy Suzuki
  4. MARS Inc., McLean, Virginia, USA.

    • Hagen Schroeter
  5. Department of Psychiatry, Columbia University, New York, New York, USA.

    • Melanie Wall
    • , Richard P Sloan
    •  & Scott A Small
  6. New York State Psychiatric Institute, New York, New York, USA.

    • Melanie Wall
    •  & Richard P Sloan
  7. Department of Radiology, Columbia University, New York, New York, USA.

    • Scott A Small


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A.M.B. designed and implemented the ModBent task and help write the manuscript. U.A.K. and F.A.P. performed the imaging analyses and help write the manuscript. L.-K.Y. aided in designing the ModBent task. W.S. administered the ModBent task to college students. H.S. aided is establishing inclusionary/exclusionary criteria for the clinical trial. M.W. performed the statistical analysis on the cognitive variables. R.P.S. was responsible for subject recruitment and characterization and helped to write the manuscript. S.A.S. designed and evaluated all the studies and was the primary writer of the manuscript.

Competing interests

H.S. is employed by MARS, Inc., a company with long-term research and commercial interests in flavanols and procyanidins.

Corresponding author

Correspondence to Scott A Small.

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  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–3 and Supplementary Tables 1 and 2

  2. 2.

    Supplementary Methods Checklist


  1. 1.

    3D surface rendering of the hippocampal formation.

    The hippocampal formations of subjects were masked and coregistered into a groupwise template. The resulting grayscale template image was thresholded and rendered in 3DSlicer using an adaptive marching cubes algorithm. The hippocampal formation is displayed in the left-anterior-oblique view and rotated clockwise.

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