In a recent study published in the journal Alzheimer’s & Dementia, researchers in the United States investigated whether daily administration of a cocoa extract (EC, comprising 500 mg of flavanols, including 80 mg of epicatechins, 50 mg/day of theobromine (50 mg/day), and 15 mg/day of caffeine) and/or an MVM (multivitamin-mineral) for three years protected cognitive function in older men and women.
To date, no cognitive protective interventions for asymptomatic older adults have been cleared by the US Food and Drug Administration (FDA). Therefore, there is an urgent need to identify safe, affordable, accessible and effective interventions to protect cognitive function in older adults and reduce the societal burden associated with Alzheimer’s disease (AD) and related dementia.
Study: Effects of cocoa extract and a multivitamin on cognitive function: A randomized clinical trial. Image Credit: ADragan/Shutterstock
About the study
In the present randomized controlled trial (RCT), researchers assessed the cognition-enhancing effects of regular use of CE and MVM in older adults.
The COcoa Supplement and Multivitamin Outcomes Study of the Mind (COSMOS-Mind) trial is ancillary to a pragmatic, placebo-controlled trial with grandparents (COSMOS) that used a two-by-two factorial design to assess the efficacy of daily administration of EC and/or MVM supplements in relation to cancer and cardiovascular disease (CVD) outcomes.
Participants in the parent trial were recruited by mail to participants in the Women’s Health Initiative extension study and Brigham and Women’s Hospital contacted participants for the vitamin D trial and Omega-3 but not randomized, as well as through commercial mailing lists and media campaigns. A total of 35,669 people participated in the COSMOS placebo trial, in which 5,432 eligible people were invited to participate in the COSMOS-Mind trial. The ancillary trial participants were recruited between August 2, 2016 and August 17, 2017. During the recruitment process for the COSMOS-Mind trial, phone calls were made to 3,223 people, of whom 2,262 eventually recruited.
The team conducted cognitive tests over the phone to assess general cognitive, executive and memory functions for three consecutive years. The primary outcome of the COSMOS-Mind study was a Global Cognition Composite (GCC) reported as z-scores and derived from mean scores of individual tests, including TICS (Cognitive Status Telephone Interview with a Short 10 minutes and a long 40-minute delay recall of word lists), Oral Track Building Test Part B (OTMT-B), Story Recall Immediate (SRI) and Delayed (SRII), Extended of Numbers (NS), Digit Order Test (DOT), and Verbal Fluency (VF). Higher scores reflected better performance.
Secondary outcomes included composite measures of episodic memory and executive function. The tertiary study outcomes were a Geriatric Depression Abbreviated Scale (GDS-SF) and a Cognitive Change Index (CCI). Additionally, the COSMOS trial monitored adverse events (AEs), and documented observed cognitive ratings were reported to the trial’s parent team.
Using the intention-to-treat (ITT) approach, the primary endpoint of the study was the alteration of GCC over the three years of cocoa extract use, and the endpoint secondary was the alteration of the GCC during the three years following the consumption of MVM supplements. Both treatments were also evaluated for their effects on memory and executive functions.
Eligibility criteria for the COSMOS trial included (i) no history of MI (myocardial infarction) or stroke; (ii) no history of cancer in the previous two years; (iii) no history of serious illness that would preclude participation; (iv) no cocoa or mineral/vitamin supplement consumption during the RCT; (v) no documented hypersensitivity to cocoa or caffeine; (vi) successful placebo run-in over ≥ 2 months with ≥ 75% intervention adherence and (vii) no concurrent participation in other RCTs.
Additionally, eligibility for the COSMOS-Mind trial included (i) patient age ≥ 65 years; (ii) no use of insulin; and (iii) ability to complete telephone cognitive assessments. The COSMOS trial was randomized using computer-generated allocation lists. All participants, examiners and investigators were masked regarding the interventions. Linear mixed effects modeling was used for the analysis.
A total of 2,262 adults were enrolled in the COSMOS-Mind trial, the average age of participants was 73, and most of them (60%) were female and non-Hispanic white (89%) . Of the entire sample population, 92%, 84%, and 79% completed the cognitive assessments during the first, second, and third years of follow-up.
CE did not significantly affect global cognition (mean z-score 0.03). In contrast, daily MVM supplementation, compared to placebo, showed statistically significant GC benefits (mean z-score of 0.1), which were greatest in adults with CVD (mean z-scores for history negative and positive history were 0.06 and 0.14, respectively.
Benefits of MVM were also observed for memory and executive functions with mean z-scores of 0.1 and 0.1, respectively, while EC did not show statistically significant results for any cognitive composite. The results were not changed in the sensitivity analysis, excluding cardiovascular patients from the analysis of the effects of the MVM intervention on global cognition.
EC did not alter the benefits of MVM on global cognition, and no AEs were reported during the trial. Cardiovascular disease patients were mostly older men with high body mass index (BMI) values, higher blood pressure records, increased statin use, higher depression, lower physical exercise and lower TICS scores.
Study results showed no cognitive benefit from daily administration of cocoa extract over three years. In contrast, daily MVM supplementation for three years improved global cognition, episodic memory, and executive functions in older adults. In particular, the benefit of MVM supplements was greater in patients with CVD.