In a recent study published in the journal Alzheimer's & Dementia, researchers in the United States investigated whether daily administration of a cocoa extract (CE, comprising 500 mg flavanols, including 80 mg epicatechins, 50 mg/day theobromine (50 mg/day), and 15mg/day caffeine) and/or an MVM (multivitamin-mineral) for three years protected cognitive functions among older men and women.
To date, no cognition-protective interventions for asymptomatic older adults have been authorized by the US (United States) FDA (food and drug administration). Therefore, there is an urgent need to identify safe, affordable, accessible, and effective interventions to protect cognitive function among elders 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 evaluated the cognition-enhancing effects of regular CE and MVM use among older individuals.
The COSMOS-Mind (COcoa Supplement and Multivitamin Outcomes Study of the Mind) trial is ancillary to a pragmatic, placebo-controlled, large parent trial (COSMOS) that used a two-by-two factorial design to assess the effectiveness of daily administration of CE and/or MVM supplementations in relation to cancer and cardiovascular disease (CVD) outcomes.
Participants in the parent trial were recruited through mailings to Women's Health Initiative Extension Study participants and Brigham and Women's Hospital to participants contacted for the vitamin D and OmegA-3 TriaL but not randomized into it, as well as through commercial mailing lists and media campaigns. In total, 35,669 individuals participated in the COSMOS placebo run, during which 5,432 eligible individuals were invited to participate in the COSMOS-Mind trial. The ancillary trial participants were enrolled between 2 August 2016 and 17 August 2017. During the recruitment process for the COSMOS-Mind trial, phone calls were made to 3,223 individuals, of which 2,262 were ultimately recruited.
The team conducted telephone-based cognitive tests to evaluate general cognition, executive, and memory functions for three consecutive years. The prime study outcome of the COSMOS-Mind trial was a global cognition composite (GCC) reported as z scores and derived from the average scores of individual tests, including the TICS (telephone interview of cognitive status with short 10-minute and long 40-minute delay recall of word lists), part B of the oral trail-making test (OTMT-B), story recall-immediate (SRI) and delayed (SRII), number span (NS), digit ordering test (DOT), and verbal fluency (VF). Higher scores reflected better performance.
Among the secondary outcomes were composite measures of episodic memory and executive function. Tertiary study outcomes were an abridged geriatric depression scale (GDS-SF) and cognitive change index (CCI). In addition, the COSMOS trial monitored adverse events (AEs), and those documented observed cognitive assessments were reported to the parent trial team.
Using the intention-to-treat (ITT) approach, the prime study endpoint was GCC alteration in the post-three years of cocoa extract usage, and the secondary study endpoint was GCC alteration in the post-three years of consuming MVM supplementations. The two treatments were also assessed for their effects on memory and executive functions.
Eligibility criteria for the COSMOS trial included (i) no prior MI (myocardial infarction) or stroke history; (ii) no prior cancer history within the previous two years; (iii) no history of serious illnesses that would preclude participation; (iv) no cocoa or mineral/vitamin supplement usage during the RCT; (v) no documented cocoa or caffeine hypersensitivity; (vi) successful placebo run-in over ≥2 months with ≥75% intervention adherence and (vii) no simultaneous participation in other RCTs.
In addition, COSMOS-Mind trial eligibility included (i) patient age ≥65 years; (ii) no insulin use; and (iii) capability to finish the telephonic cognitive assessments. The COSMOS trial was randomized using computer-generated allocation listings. All participants, examiners, and investigators were masked concerning the interventions. Linear mixed-effect modeling was used for the analysis.
In total, 2,262 adults were enrolled for the COSMOS-Mind trial, the average age of the participants was 73 years, and most of them (60%) were women and non-Hispanic Whites (89%). Out of the total sample population, 92%, 84%, and 79% completed the cognitive assessments in the first, second, and third follow-up years.
CE did not significantly affect global cognition (average z score 0.03). On the contrary, daily MVM supplementation, compared to the placebo, showed statistically significant GC benefits (average z score 0.1), which were most prominent among adults with CVD (average z scores for negative history and positive history were 0.06 and 0.14, respectively.
MVM benefits were also observed for memory and executive functions with average z scores of 0.1 and 0.1, respectively, whereas CE did not show statically significant results for any cognitive composite. The findings were unaltered in the sensitivity analysis, excluding CVD patients from analyzing MVM intervention effects on global cognition.
CE did not alter MVM benefits on global cognition, and there were no reported AEs during the trial. CVD patients were predominantly older males with elevated body mass index (BMI) values, higher blood pressure recordings, increased statin usage, more significant depression, lower physical exercise, and lesser TICS scores.
The study findings showed no cognitive benefit of daily cocoa extract administration over three years. In contrast, daily MVM supplementation for three years improved global cognition, episodic memory, and executive functions among older individuals. In particular, the benefit of MVM supplements was more significant among CVD patients.