Insights into the role of diet and dietary flavanols in cognitive aging: results of a randomized controlled trial

Abstract

With the world's population aging, age-related memory decline is an impending cognitive epidemic. Assessing the impact of diet on cognitive aging, we conducted a controlled, randomized, parallel-arm dietary intervention with 211 healthy adults (50-75 years) investigating effects of either a placebo or 260, 510 and 770 mg/day of cocoa flavanols for 12-weeks followed by 8-weeks washout. The primary outcome was a newly-developed object-recognition task localized to the hippocampus' dentate gyrus. Secondary outcomes included a hippocampal-dependent list-learning task and a prefrontal cortex-dependent list-sorting task. The alternative Healthy Eating Index and a biomarker of flavanol intake (gVLM) were measured. In an MRI substudy, hippocampal cerebral blood volume was mapped. Object-recognition and list-sorting performance did not correlate with baseline diet quality and did not improve after flavanol intake. However, the hippocampal-dependent list-learning performance was directly associated with baseline diet quality and improved after flavanol intake, particularly in participants in the bottom tertile of baseline diet quality. In the imaging substudy, a region-of-interest analysis was negative but a voxel-based-analysis suggested that dietary flavanols target the dentate gyrus. While replication is needed, these findings suggest that diet in general, and dietary flavanols in particular, may be associated with memory function of the aging hippocampus and normal cognitive decline.

Conflict of interest statement

HS is employed by Mars, Incorporated, a company engaged in flavanol research and flavanol-related commercial activities. SAS has received an unrestricted research grant from Mars, Incorporated. None of the other authors has a conflict of interest to declare.

Figures

Figure 1

Example of the neuropsychological tests used to assess cognitive performance, including (a) Object-Recognition test (Modified Benton recognition task), (b) List-Learning memory test (Modified Rey auditory verbal learning test), and (c) List-Sorting task (List sorting working memory test from the NIH Toolbox Cognition Battery). Example stimuli for the ModBent (a) were generated in MATLAB (MathWorks, Natick, MA, version R2008a). Details of stimuli generation were described previously. Stimuli displayed as examples from NIH Toolbox were publicly available clip art. We did not include stimuli from the actual tests to maintain the integrity and security of test materials, according to the ethical standards of our field. Information about the NIH Toolbox is available online (https://www.healthmeasures.net/explore-measurement-systems/nih-toolbox).

Figure 2

CONSORT diagram.

Figure 3

Concentration of 5-(3ʹ,4ʹ-dihydroxyphenyl)-γ-valerolactone metabolites (gVLM) in plasma at baseline, 12 weeks after daily intake of placebo and flavanols at a low (260 mg), medium (510 mg) and high (770 mg) intake level, and at 20 weeks after washout (8 weeks). Data are presented as the individual concentration of gVLM for each volunteer (black lines) and as the mean (red dashed line) over time.

Figure 4

Changes in List-Learning memory test before and 12 weeks after daily intake of placebo and flavanols at a low (260 mg), medium (510 mg) and high (770 mg) intake level. Data are expressed as mean ± SE of all volunteers (a) and divided in tertiles according to diet quality assessed with the alternative Healthy Eating Index (aHEI; b).

Figure 5

(a) Hippocampal sub-regions. (b) Predetermined region-of-interest (ROI) in the Dentate Gyrus used to evaluate the effect of flavanol consumption by Cerebral Blood Volume (CBV)-fMRI. (c) Changes in CBV-fMRI before and 12 weeks after daily intake of placebo and flavanols at a low (260 mg), medium (510 mg) and high (770 mg) intake level. Data are expressed as mean ± SE adjusted by baseline values.