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Investigating the Effects of Cocoa Flavanol on Cognition Assessed Online

Not Applicable
Completed
Conditions
Aging
Cognitive Change
Interventions
Dietary Supplement: Cocoa Extract
Dietary Supplement: Cocoa Extract Placebo
Dietary Supplement: Multivitamin placebo
Dietary Supplement: Multivitamin
Registration Number
NCT04582617
Lead Sponsor
Columbia University
Brief Summary

The COcoa Supplement and Multivitamin Outcomes Study (COSMOS; NCT02422745) is a randomized clinical trial of cocoa extract supplement (containing a total of 500 mg/d flavanols, including 80 mg (-)-epicatechin), and/or a standard multivitamin supplement to reduce the risk of cardiovascular disease and cancer among men aged 60 years and older and women aged 65 years and older. This ancillary study (COSMOS Web) is being conducted among a subset of participants in COSMOS and will examine whether the cocoa extract supplements affects cognitive function in older adults.

Detailed Description

The goal of the COSMOS Web study is to determine whether a dietary intervention with flavanol-containing cocoa extract has an effect on cognitive function in older adults (age 60+). The study will be conducted in a subset of 4000 participants from the COSMOS study (NCT02422745). The investigators' recent work (Sloan et al., submitted) showed that cocoa flavanol consumption over 12 weeks led to improvements in immediate recall on the ModRey verbal memory task in healthy older adults.

In COSMOS Web, the investigators are testing the effect of a dietary intervention with flavanol-containing cocoa extract on a range of aging-related cognitive measures, as assessed through a novel online-administered test battery, in a cohort of older participants. Change in ModRey (Modified Rey Auditory Verbal Learning Test) immediate recall performance over 1 year of cocoa extract consumption will be our primary outcome measure. Secondary endpoints will include change in ModRey performance at 2- and 3-year follow-up, and change in performance tests of a novel object recognition task, executive function/working memory, and spatial memory at 1-, 2-, and 3- years follow-up. This study will explore whether baseline measures of cognition and nutritional status can predict differential effects of the cocoa extract supplementation. This study will also explore the effect of multivitamin intake on the primary and secondary outcomes noted above and test whether multivitamin intake interacts with flavanol intake from cocoa extract to enhance or mitigate effects on cognitive outcomes. In a subset of participants evaluated in person, this study will examine the impact of cocoa extract intake and explore the main and interacting effects of multivitamins on cognitive changes and brain structure and function appreciated with magnetic resonance imaging over a 2-year period.

Leveraging the COSMOS study, which has randomized 21,442 older adult participants into cocoa extract and placebo interventions, the study team at Brigham and Women's Hospital, who administer the parent COSMOS trial, are recruiting \~4000 older adult volunteers to participate in COSMOS Web (this study) an online cognitive testing battery developed by the team at Columbia University. These 4000 participants will complete an initial online cognitive assessment and additional assessments after one, two, and three years of follow-up. In addition, approximately 200 COSMOS Web participants who live in the Boston area will complete clinic-based study visits at the Clinical and Translational Science Center at Brigham and Women's Hospital. During that visit, they will complete a neuropsychological test battery, for comparison to their performance online. This study will examine the impact of dietary interventions with cocoa extract and explore the main and interacting effects of multivitamin intake on cognitive changes and brain structure and function appreciated with magnetic resonance imaging over a 2-year period.

After the COSMOS trial began, an advanced method to analyze cocoa flavanols was accredited by AOAC International as a First Action Official Method of Analysis (https://doi.org/10.1093/jaoacint/qsaa132). This updated method relies on a reference material (RM8403) recently standardized and made commercially available by the U.S. National Institute of Standards and Technology. While the actual cocoa flavanol content of the COSMOS intervention remained unchanged throughout the trial, the application of this new analytical method led to expected changes in how the total cocoa flavanol content is now reported. Applying AOAC 2020.05/RM8403 to the COSMOS intervention, the total cocoa flavanol content of the COSMOS intervention is now 500 mg/day. Reporting of (-)-epicatechin content remained unaffected. Going forward, we will therefore apply AOAC 2020.05/RM8403 and report that the COSMOS intervention tested 500 mg/day of cocoa flavanols, including 80 mg of (-)-epicatechin.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
3959
Inclusion Criteria
  • Willingness to participate
  • Email and internet access via computer
Exclusion Criteria

* Analog to COSMOS parent trial

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
Cocoa extract placebo + multivitamin placeboMultivitamin placebo-
Cocoa extract + multivitaminCocoa Extract-
Cocoa extract + multivitaminMultivitamin-
Cocoa extract + multivitamin placeboCocoa Extract-
Cocoa extract placebo + multivitamin placeboCocoa Extract Placebo-
Cocoa extract placebo + multivitaminCocoa Extract Placebo-
Cocoa extract + multivitamin placeboMultivitamin placebo-
Cocoa extract placebo + multivitaminMultivitamin-
Primary Outcome Measures
NameTimeMethod
ModRey: 1-Year Change in Immediate Recall/Learning/Episodic Memory1-year follow-up

A measure of verbal memory. The change in the number of words recalled immediately on the ModRey task (Hale et al., 2019), after one year of cocoa extract/placebo intervention.

Secondary Outcome Measures
NameTimeMethod
Hippocampal cerebral blood volume change2-year follow-up

Change in cerebral blood volume in the hippocampus (in cubic mm) in subset of participants with in-clinic MRI scan

ModRey: Longitudinal Change in Immediate Recall/Learning2-year and 3-year follow-ups

A measure of verbal memory. Change in number of words recalled immediately on the ModRey task.

Flanker: Directional Flanker Effect1-year, 2-year and 3-year follow-ups

A measure of executive control. Change in the difference in reaction time (in ms) between directionally congruent and directional incongruent trials in a Flanker task.

Self-Reported Memory Change1-year, 2-year and 3-year follow-ups

Self-report of memory change in the last year, on a scale of 1-7

In-clinic ModBent2-year follow-up

Change in performance on the ModBent task, administered in-clinic to a subset of 200 participants

Hippocampal volume change2-year follow-up

Change in hippocampus volume (in cubic mm) in subset of participants with in-clinic MRI scan

Global cortical thickness change2-year follow-up

Change in average cortical thickness in the whole brain (in mm) in subset of participants with in-clinic MRI scan

ModBent1-year, 2-year and 3-year follow-ups

A measure of pattern separation/object recognition. Change in the mean response time on correct rejection trials on a delayed recognition task.

Spatial Reconstruction: Distortion1-year, 2-year and 3-year follow-ups

A measure of spatial memory. Change in the proportion of stimulus pairs where their relative locations are reconstructed differently than originally shown

Proportions of words recalled on in-clinic list learning task2-year follow-up

Proportions of words recalled on list learning task for subset of participants with in-clinic cognitive testing

Interaction of Baseline Diet & Intervention on the ModRey1-year, 2-year and 3-year follow-ups

Interaction of baseline diet (as assessed by the Food Frequency Questionnaire) with the flavanol/multivitamin interventions on the ModRey, a measure of verbal memory (change in number of words recalled)

Trial Locations

Locations (2)

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

Columbia University Irving Medical Center

🇺🇸

New York, New York, United States

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