Maintenance of cognitive abilities is of critical importance to older adults, yet few effective strategies to mitigate cognitive decline currently exist. 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 is associated with the hippocampal-dependent memory component of cognitive aging and that memory benefits of a flavanol intervention might depend on habitual diet quality. Multivitamin supplementation is used to promote general health, but it is unclear whether it favorably affects cognition in older age. The purpose of this clinical trial was to test the primary hypotheses that dietary flavanol and multivitamin supplementation improves memory in older adults and the secondary hypothesis that the effect of flavanol supplementation on memory is moderated by baseline diet quality.

The COcoa Supplement and Multivitamin Outcomes Study Web (COSMOS-Web) ancillary study (NCT04582617) included 3562 older adults. In this two-by-two factorial, 3-year trial, participants were randomly assigned to one of four treatment arms, comprising cocoa extract (500 mg of dietary flavanols per day), a daily multivitamin (Centrum Silver), and/or placebo. Participants were evaluated annually with an Internet-based battery of neuropsychological tests for 3 years. The prespecified primary outcome measure was change in episodic memory, operationally defined as immediate recall performance on the ModRey test, after 1 year of intervention. Secondary outcome measures included changes in episodic memory over 3 years of follow-up and changes in performance on neuropsychological tasks of novel object recognition and executive function over 3 years. We also tested whether the effect of dietary flavanol supplementation varied as a function of baseline diet quality, reflected by the alternative Healthy Eating Index, and, in a subset, by baseline levels of a urine-based biomarker of flavanol intake.

The flavanol intervention improved memory at year 1 among participants in lower tertiles of habitual diet quality or habitual flavanol consumption based on the urine biomarker, subgroups with lower memory performance at baseline. Increases in the flavanol biomarker over the course of the trial were associated with improving memory. The multivitamin supplement improved memory at 1 year as well as across the 3 y of follow-up on average. Neither flavanol nor multivitamin supplementation affected secondary outcomes or interacted with each other on primary or secondary outcomes.

Dietary flavanols can 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. Daily multivitamin supplementation improves memory in older adults, irrespective of baseline diet. Multivitamin supplementation holds promise as a safe and accessible approach to maintaining cognitive health in older age.