Dietary flavanols restore hippocampal-dependent memory in older adults with lower diet quality and lower habitual flavanol consumption

Author:

Brickman Adam M.123,Yeung Lok-Kin123,Alschuler Daniel M.4ORCID,Ottaviani Javier I.5ORCID,Kuhnle Gunter G. C.6ORCID,Sloan Richard P.47ORCID,Luttmann-Gibson Heike89ORCID,Copeland Trisha8,Schroeter Hagen5ORCID,Sesso Howard D.810ORCID,Manson JoAnn E.810ORCID,Wall Melanie47,Small Scott A.1237ORCID

Affiliation:

1. Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032

2. Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032

3. Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032

4. Mental Health Data Science Area, New York State Psychiatric Institute, New York, NY 10032

5. Mars Inc., 6885 Elm St, McLean, VA 22101

6. Department of Food and Nutritional Sciences, Hugh Sinclair Unit of Human Nutrition, University of Reading, Reading RG6 6DZ, United Kingdom

7. Department of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032

8. Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115

9. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115

10. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115

Abstract

Dietary flavanols are food constituents found in certain fruits and vegetables that have been linked to cognitive aging. Previous studies suggested that consumption of dietary flavanols might specifically be associated with the hippocampal-dependent memory component of cognitive aging and that memory benefits of a flavanol intervention might depend on habitual diet quality. Here, we tested these hypotheses in the context of a large-scale study of 3,562 older adults, who were randomly assigned to a 3-y intervention of cocoa extract (500 mg of cocoa flavanols per day) or a placebo [(COcoa Supplement and Multivitamin Outcomes Study) COSMOS-Web, NCT04582617]. Using the alternative Healthy Eating Index in all participants and a urine-based biomarker of flavanol intake in a subset of participants [n = 1,361], we show that habitual flavanol consumption and diet quality at baseline are positively and selectively correlated with hippocampal-dependent memory. While the prespecified primary end point testing for an intervention-related improvement in memory in all participants after 1 y was not statistically significant, the flavanol intervention restored memory among participants in lower tertiles of habitual diet quality or habitual flavanol consumption. Increases in the flavanol biomarker over the course of the trial were associated with improving memory. Collectively, our results allow dietary flavanols to be considered in the context of a depletion–repletion paradigm and suggest that low flavanol consumption can act as a driver of the hippocampal-dependent component of cognitive aging.

Funder

Mars Edge

NIH

S Department of Health and Human Services

Nathaniel Wharton Fund

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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