An observational study in Cognitive Impairment, Dementia and Aging, sponsored by Wake Forest University Health Sciences. Completed at 1 site in United States. Open to participants aged 65 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-08-22.
Sponsored by Wake Forest University Health Sciences · Observational
The parent trial (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. (-)-epicatechins), and 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. A cognitive ancillary study (COSMOS-Mind) is being conducted among men and women, 65 years and older, who are enrolled in COSMOS and will examine whether the cocoa extract supplement or the multivitamin supplement improves cognitive function and reduces risk of cognitive impairment, including Alzheimer's disease (AD) and other related types of dementia. Participants at the Wake Forest site will only be getting a phone call.
Identifying a safe, affordable, and well-tolerated intervention that prevents cognitive decline in older adults is of critical public health importance. There is compelling evidence from basic science, and small clinical studies that cocoa flavanols may protect cognitive function in older adults and reduce risk of Alzheimer's disease (AD) and related dementia. Thus, this intervention could have important downstream benefits for health care utilization and cost, caregiver burden, and overall quality of life for older adults. Cocoa flavanol effects on cognition, however, need to be assessed in a definitive clinical trial.
The parent trial (COSMOS) will enroll 21,442 women and men nationwide, drawn from the Women's Health Initiative (WHI) participant cohort and the VITamin D and OmegA-3 TriaL (VITAL) non-randomized respondent cohort, and will be conducted primarily by mail to assess whether high-potency cocoa flavanol extract and a multivitamin - alone or in combination - will reduce risk of cardiovascular disease and cancer over 3 years of follow-up.
After the COSMOS trial began, an advanced method to analyze cocoa flavanols was accredited by Association of Official Agricultural Chemists (AOAC) International as a First Action Official Method of Analysis https://doi.org/10.1093/jaoacint/qsaa132 [secure-web.cisco.com]). 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, this record 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.
Once participants are enrolled in COSMOS, the study team at Brigham and Women's Hospital will provide contact information and other parent trial outcomes for COSMOS-Mind participants to the Wake Forest team using a secure web-based data transfer system. This seamless exchange of information between sites will permit timely accounting to ensure that the targeted demographics for enrollment are achieved (e.g. gender, age, race, ethnicity).
COSMOS-Mind will only be administered a telephone cognitive assessment to all participants at enrollment (baseline), and annually for 3 years of follow-up by trained and certified staff of the Wake Forest COSMOS-Mind team.
3,843 studies on the registry are indexed under Cognitive Dysfunction; 1,099 are open to participants now.
This study's enrollment of 2,262 is above the median of 150 across 950 observational studies indexed under Cognitive Dysfunction.
Browse Cognitive Dysfunction studies →Wake Forest University Health Sciences is the lead sponsor of 1,320 studies on the registry; 199 are open to participants now.
Of its 323 completed or terminated interventional studies of FDA-regulated products, 243 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
COSMOS-Mind will include 2,000 participants from the COSMOS parent trial who are at least 65 years of age, with approximately equal distribution of women and men.
Participants in COSMOS (NCT02422745) who meet the following criteria are eligible to participate in this ancillary study:
Inclusion Criteria -
Exclusion Criteria -
2 capsules containing 500 mg/d cocoa extract; daily MTV
2 capsules containing 500 mg/d cocoa extract; daily MTV placebo
Cocoa extract placebo (2 capsules/d); daily MTV
Cocoa extract placebo (2 capsules/d); daily MTV placebo
Global Cognitive Function: Average Change Over Follow-up From Baseline
A composite cognitive measure that averages individual test z-scores of the Telephone Interview for Cognitive Status-modified (TICSm) Total and Long, the Immediate and Delayed Story Recall tests, the Oral Trail Making A and B tests (log-transformed), the Category Fluency and Verbal Fluency tests, and the Number Span Backward and Forward tests. Scores are ordered so that better performance corresponds to higher positive scores. Longitudinal data are used to create a linear contrast for the primary analysis to compare the difference between the average of scores at Years 1, 2, and 3 and the baseline score, i.e. (z1+z2+z3)/3 - z0, where z's denote the composited measures at baseline and years 1-3. This contrast is fitted using a random effects model for repeated measures. The primary comparison is for the margins of the factorial design: active cocoa flavonal (with or without active multivitamin) versus placebo flavonal (with or without active multivitamin).
Time frame: From Baseline through Year 3
Composite Cognitive Function
A composite cognitive measure that averages individual test z-scores of the Telephone Interview for Cognitive Status-modified (TICSm) Total and Long, the Immediate and Delayed Story Recall tests, the Oral Trail Making A and B tests (log-transformed), the Category Fluency and Verbal Fluency tests, and the Number Span Backward and Forward tests. Scores are ordered so that better performance corresponds to higher positive scores. Longitudinal data are used to create a linear contrast for the primary analysis to compare the difference between the average of scores at Years 1, 2, and 3 and the baseline score, i.e. (z1+z2+z3)/3 - z0, where z's denote the composited measures at baseline and years 1-3. This contrast is fitted using a random effects model for repeated measures. The comparison for this secondary outcome is based on the margins of the factorial design to compare multivitamin (with or without cocoa flavonal) with multivitamin placebo (with or without cocoa flavonal)
Time frame: From baseline through year 3
Incident Mild Cognitive Impairment
Mild cognitive impairment based on centralized adjudication of cognitive test scores and input from a proxy. Limited to participants free of mild cognitive impairment at baseline. Incidence over 3 years of follow-up.
Time frame: From baseline through year 3
Incidence of Mild Cognitive Impairment Among Those Free at Baseline
Mild cognitive impairment based on central adjudication of test scores with input from proxies. Based on test scores administered annually across 3 years.
Time frame: From baseline through year 3
Executive Function
Average of z-scores for the following tests: Oral Trail Making Test - B (log-transformed), Category Verbal Fluency, Letter Verbal Fluency, Number Span Test (Backwards and Forward). Higher (positive) scores reflect better performance. Linear contrast of scores collected at baseline, year 1, year 2, and year 3: (z1+z2+z3)/3 - z0)
Time frame: From baseline through year 3
Episodic Memory
Average z-scores from Telephone Interview for Cognitive Status-modified Delayed Word List, Story Immediate Recall, Story Delayed Recall. Higher (positive) scores reflect better performance. Annual test administrations.
Time frame: From baseline through year 3
Executive Function
Average of z-scores for the following tests: Oral Trail Making Test - B (log-transformed), Category Verbal Fluency, Letter Verbal Fluency, Number Span Test (Backwards and Forward). Higher (positive) scores reflect better performance. Tests administered annually.
Time frame: From baseline through year 3
Episodic Memory
Average z-scores from Telephone Interview for Cognitive Status-modified Delayed Word List, Story Immediate Recall, Story Delayed Recall. Higher (positive) scores reflect better performance.
Time frame: From baseline through year 3
| Milestone | Cocoa Extract + Multivitamin | Cocoa Extract + Multivitamin Placebo | Cocoa Extract Placebo + Multivitamin | Cocoa Extract Placebo + Multivitamin Placebo |
|---|---|---|---|---|
| Started | 571 | 553 | 551 | 587 |
| Completed | 444 | 441 | 441 | 462 |
| Not completed | 127 | 112 | 110 | 125 |
| Withdrew: Death | 9 | 12 | 9 | 10 |
| Withdrew: Withdrawal by subject | 51 | 49 | 37 | 46 |
| Withdrew: Lost to follow-up | 67 | 51 | 64 | 69 |
A composite cognitive measure that averages individual test z-scores of the Telephone Interview for Cognitive Status-modified (TICSm) Total and Long, the Immediate and Delayed Story Recall tests, the Oral Trail Making A and B tests (log-transformed), the Category Fluency and Verbal Fluency tests, and the Number Span Backward and Forward tests. Scores are ordered so that better performance corresponds to higher positive scores. Longitudinal data are used to create a linear contrast for the primary analysis to compare the difference between the average of scores at Years 1, 2, and 3 and the baseline score, i.e. (z1+z2+z3)/3 - z0, where z's denote the composited measures at baseline and years 1-3. This contrast is fitted using a random effects model for repeated measures. The primary comparison is for the margins of the factorial design: active cocoa flavonal (with or without active multivitamin) versus placebo flavonal (with or without active multivitamin).
| score on a scale | Cocoa Extract + Multivitamin | Cocoa Extract + Multivitamin Placebo | Cocoa Extract Placebo + Multivitamin | Cocoa Extract Placebo + Multivitamin Placebo |
|---|---|---|---|---|
| Global Cognitive Function: Average Change Over Follow-up From Baseline | 0.24 ± 0.02 | 0.15 ± 0.02 | 0.20 ± 0.02 | 0.15 ± 0.02 |
A composite cognitive measure that averages individual test z-scores of the Telephone Interview for Cognitive Status-modified (TICSm) Total and Long, the Immediate and Delayed Story Recall tests, the Oral Trail Making A and B tests (log-transformed), the Category Fluency and Verbal Fluency tests, and the Number Span Backward and Forward tests. Scores are ordered so that better performance corresponds to higher positive scores. Longitudinal data are used to create a linear contrast for the primary analysis to compare the difference between the average of scores at Years 1, 2, and 3 and the baseline score, i.e. (z1+z2+z3)/3 - z0, where z's denote the composited measures at baseline and years 1-3. This contrast is fitted using a random effects model for repeated measures. The comparison for this secondary outcome is based on the margins of the factorial design to compare multivitamin (with or without cocoa flavonal) with multivitamin placebo (with or without cocoa flavonal)
| score on a scale | Cocoa Extract + Multivitamin | Cocoa Extract + Multivitamin Placebo | Cocoa Extract Placebo + Multivitamin | Cocoa Extract Placebo + Multivitamin Placebo |
|---|---|---|---|---|
| Composite Cognitive Function | 0.24 ± 0.02 | 0.15 ± 0.02 | 0.20 ± 0.02 | 0.15 ± 0.02 |
Mild cognitive impairment based on centralized adjudication of cognitive test scores and input from a proxy. Limited to participants free of mild cognitive impairment at baseline. Incidence over 3 years of follow-up.
| Participants | Cocoa Extract | Cocoa Extract Placebo |
|---|---|---|
| Incident Mild Cognitive Impairment | 47 | 63 |
Mild cognitive impairment based on central adjudication of test scores with input from proxies. Based on test scores administered annually across 3 years.
| Participants | Multivitamin | Multivitamin Placebo |
|---|---|---|
| Incidence of Mild Cognitive Impairment Among Those Free at Baseline | 53 | 57 |
Average of z-scores for the following tests: Oral Trail Making Test - B (log-transformed), Category Verbal Fluency, Letter Verbal Fluency, Number Span Test (Backwards and Forward). Higher (positive) scores reflect better performance. Linear contrast of scores collected at baseline, year 1, year 2, and year 3: (z1+z2+z3)/3 - z0)
| score on a scale | Cocoa Extract | Cocoa Extract Placebo |
|---|---|---|
| Executive Function | 0.06 ± 0.02 | 0.04 ± 0.02 |
Average z-scores from Telephone Interview for Cognitive Status-modified Delayed Word List, Story Immediate Recall, Story Delayed Recall. Higher (positive) scores reflect better performance. Annual test administrations.
| score on a scale | Cocoa Extract | Cocoa Extract Placebo |
|---|---|---|
| Episodic Memory | 0.29 ± 0.02 | 0.27 ± 0.02 |
Average of z-scores for the following tests: Oral Trail Making Test - B (log-transformed), Category Verbal Fluency, Letter Verbal Fluency, Number Span Test (Backwards and Forward). Higher (positive) scores reflect better performance. Tests administered annually.
| score on a scale | Multivitamin | Multivitamin Placebo |
|---|---|---|
| Executive Function | 0.08 ± 0.02 | 0.02 ± 0.02 |
Average z-scores from Telephone Interview for Cognitive Status-modified Delayed Word List, Story Immediate Recall, Story Delayed Recall. Higher (positive) scores reflect better performance.
| score on a scale | Multivitamin | Multivitamin Placebo |
|---|---|---|
| Episodic Memory | 0.31 ± 0.02 | 0.25 ± 0.02 |
Collected over Across all follow-up -- 3 years.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cocoa Extract + Multivitamin | — | — | — |
| Cocoa Extract + Multivitamin Placebo | — | — | — |
| Cocoa Extract Placebo + Multivitamin | — | — | — |
| Cocoa Extract Placebo + Multivitamin Placebo | — | — | — |
| Age, Continuous(years) | Cocoa Extract + Multivitamin | Cocoa Extract + Multivitamin Placebo | Cocoa Extract Placebo + Multivitamin | Cocoa Extract Placebo + Multivitamin Placebo | Total |
|---|---|---|---|---|---|
| Mean | 72.7 ± 5.5 | 73.2 ± 5.6 | 72.9 ± 5.6 | 73.1 ± 5.7 | 73.0 ± 5.6 |
| Sex: Female, Male(Participants) | Cocoa Extract + Multivitamin | Cocoa Extract + Multivitamin Placebo | Cocoa Extract Placebo + Multivitamin | Cocoa Extract Placebo + Multivitamin Placebo | Total |
|---|---|---|---|---|---|
| Female | 339 | 330 | 319 | 360 | 1348 |
| Male | 232 | 223 | 232 | 227 | 914 |
| Race/Ethnicity, Customized(Participants) | Cocoa Extract + Multivitamin | Cocoa Extract + Multivitamin Placebo | Cocoa Extract Placebo + Multivitamin | Cocoa Extract Placebo + Multivitamin Placebo | Total |
|---|---|---|---|---|---|
| American Indian/Alaska Native | 2 | 1 | 8 | 2 | 13 |
| Asian/Pacific Islander | 9 | 12 | 10 | 8 | 39 |
| Black/African American | 40 | 23 | 34 | 34 | 131 |
| Hispanic | 13 | 18 | 15 | 21 | 67 |
| Multiracial/Unknown | 1 | 1 | 2 | 2 | 6 |
| Non-Hispanic White | 506 | 498 | 482 | 520 | 2006 |
| Region of Enrollment(participants) | Cocoa Extract + Multivitamin | Cocoa Extract + Multivitamin Placebo | Cocoa Extract Placebo + Multivitamin | Cocoa Extract Placebo + Multivitamin Placebo | Total |
|---|---|---|---|---|---|
| United States | 571 | 553 | 551 | 587 | 2262 |
| Global Cognitive Composite(z-scores) | Cocoa Extract + Multivitamin | Cocoa Extract + Multivitamin Placebo | Cocoa Extract Placebo + Multivitamin | Cocoa Extract Placebo + Multivitamin Placebo | Total |
|---|---|---|---|---|---|
| Mean | -0.01 ± 0.99 | 0.02 ± 1.00 | 0.05 ± 1.02 | -0.05 ± 0.99 | 0.00 ± 1.00 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — COSMOS-Mind and COSMOS (parent trial, PI: Manson and Sesso) have data transfer procedures and protocols in place which use password protection and encryption, to permit seamless and secure exchange of information. Safety monitoring will be completed through the parent trial. The COSMOS-Mind staff will send all adverse events reported to them to the parent trial for reporting and follow-up. This data will be sent electronically only to approved users through a protected network.
Supporting information: Study protocol, Icf
This study is completed, as verified in May 2023. You cannot join it, but the record below documents what was studied.
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Wake Forest University Health Sciences