A multivitamin taken daily for three years has been linked to a 60% slowing of cognitive ageing, with the effects especially pronounced in patients with cardiovascular (CVD) disease, according to a study presented at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
In addition to testing the effect of a daily multivitamin on cognition, the COSMOS-Mind study also examined the effect of cocoa flavanols, but showed no beneficial effect, reports Medscape.
The findings “may have important public health implications, particularly for brain health, given the accessibility of multivitamins and minerals, and their low cost and safety”, said study investigator Laura Baker, professor, Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Previously, the effect of multivitamin-mineral (MVM) supplementation on cognition had been tested in only one large randomised clinical trial, the Physicians Health Study II. That study did not show an effect, but included only older male physicians and cognitive testing began 2.5 years after randomisation.
“Our study provides new evidence that daily multivitamin supplementation may benefit cognitive function in older women and men, and the multivitamin effects may be more pronounced in participants with cardiovascular disease.”
For effects of multivitamins on Alzheimer’s disease prevalence and progression, “stay tuned”, Baker concluded.
The study is a sub-study of a large parent trial comparing the effects of cocoa extract (500 mg/day cocoa flavanols) and a standard MVM)to placebo on cardiovascular and cancer outcomes in more than 21,000 older participants.
COSMOS-Mind included 2,262 adults aged 65 and over without dementia who underwent cognitive testing at baseline and annually for three years. The mean age at baseline was 73 years, and 40.4% were men. Most participants (88.7%) were non-Hispanic white and almost half (49.2%) had some post-college education.
All study groups were balanced with respect to demographics, CVD history, diabetes, depression, smoking status, alcohol intake, chocolate intake and prior multivitamin use. Baseline cognitive scores were also similar between study groups. Researchers had complete data on 77% of study participants.
The primary endpoint was the effect of cocoa extract (CE) vs placebo on Global Cognitive Function composite score. The secondary outcome was the effect of MVM vs placebo on global cognitive function.
Additional outcomes included the impact of supplements on executive function and memory and the treatment effects for prespecified subgroups, including subjects with a history of CVD.
Using a graph of change over time, Baker showed there was no effect of cocoa on global cognitive function. “We see the to-be-expected practice effects, but there’s no separation between the active and placebo groups,” she said.
It was a different story for MVM. Here, there was the same practice effect, but the graph showed the lines separated for global cognitive function composite score .
“We see a positive effect of multivitamins for the active group relative to placebo, peaking at two years and then remaining stable over time,” said Baker.
There were similar findings with MVM for the memory composite score, and the executive function composite score. “We have significance in all three, where the two lines do separate over and above the practice effects,” said Baker.
Investigators found a baseline history of CVD, including transient ischaemic attack, congestive heart failure, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, and stent, but not myocardial infarction or stroke as these were excluded in the parent trial because they affected the response to multivitamins.
As expected, those with CVD had lower cognitive scores at baseline. “But after an initial bump due to practice effect, at year one, the cardiovascular disease history folks continue to benefit from multivitamins, whereas those who got placebo multivitamins continue to decline over time,” said Baker.
Based on information from a baseline scatter plot of cognitive function scores by age, the study’s modelling estimated the multivitamin treatment effect had a positive benefit of .028 standard deviations (SD) per year.
“Daily multivitamin-mineral supplementation appears to slow cognitive ageing by 60% or by 1.8 years,” Baker added.
After the presentation, session co-chair Dr Suzanne Schindler, instructor, Department of Neurology, Washington University School of Medicine, St Louis, Missouri, said she and her colleagues “always check vitamin B12 levels” in patients with memory and cognitive difficulties and wondered if study subjects with a low level or deficiency of vitamin B12 benefited from the intervention.
“We are asking ourselves that as well,” said Baker. “Some of this is a work in progress. We still need to look at that more in-depth to understand whether it might be a mechanism for improvement. I think the results are still out on that topic.”
Study details
IMPACT OF COCOA FLAVANOLS AND MULTIVITAMINS ON COGNITIVE FUNCTION: FINDINGS OF THE COCOA SUPPLEMENT AND MULTIVITAMIN OUTCOMES STUDY OF COGNITION (COSMOS-MIND).
Laura Baker, Joann Manson, Stephen Rapp, Howard Sesso , Sarah Gaussoin, Sally Shumaker , Mark Espeland
Published in JPAD 13 November 2021
Background
COSMOS-Mind examined whether daily treatment with cocoa flavanol extract (CF) versus placebo or standard multivitamin-multimineral (MVM; Centrum Silver) versus placebo for 3 years in adults aged ≥65 years protected cognitive function and slowed cognitive decline associated with normal and pathological aging, including Alzheimer’s disease (AD). COSMOS-Mind is an ancillary study to the large 2×2 factorial randomised controlled trial, COcoa Supplement and Multivitamin Outcomes Study (COSMOS; NCT102422745; MPI: Manson, Sesso, Anderson) that tests the effects of these supplements on cardiovascular disease and cancer.
Epidemiologic evidence suggests that higher flavonoid intake is associated with lower risk for cognitive decline and AD, and two small, controlled trials provided evidence of short-term cognition-enhancing effects of CF. Although essential nutrient deficiencies have been linked to higher risk of cognitive decline and AD, evidence to support MVM supplementation for cognitive benefit is inconsistent. Most trials examining MVM effects on cognition included relatively healthy cohorts (e.g., the Physicians’ Health Study) or relied on individual test scores rather than a multi-test composite to assess treatment effects.
COSMOS-Mind provides an important opportunity to further examine the effects of long-term MVM and CF supplementation on a composite measure of global cognitive function in a large and diverse sample of older adults.
Objectives
To test whether randomised assignment to daily CF (primary aim) and/or MVM (secondary aim) affects cognitive function across 3 years in non-demented adults aged ≥65 years.
Methods
COSMOSMind methods are published (Baker et al., Contemporary Clinical Trials 2019;83:57-63). The study targeted enrollment of 2,000 participants from the planned 18,000-person parent trial to provide >90% statistical power to detect mean cognitive change over 3 years of annual follow-up. Interested participants from S20 the parent trial were recruited into COSMOS-Mind.
Participants were consented by telephone, and a 45-minute telephone-based cognitive battery was administered at baseline and annually at years 1, 2, and 3. Supplements and placebos were distributed by mail. Cognitive tests administered included the Telephone Interview of Cognitive Status-modified (TICSm), Delayed Word Recall, Story Recall, Oral Trail-Making Test, Verbal Fluency, Number Span and Digit Ordering. Cognitive outcomes for analysis included composite scores of global cognitive function, episodic memory and executive function (all converted to z-scores). Statistical analyses (intention-to-treat) were based on mixed effects models in which constituent test scores for the composite outcome (baseline through year 3 for all participants) were included as dependent variables and linear contrasts were used to assess two-tailed differences between the average mean scores across follow-up and the baseline mean score.
Interactions between treatment groups (CF, MVM) were explored, and multiple imputation was used to examine the influence of missing data. Results: COSMOS-Mind enrolled 2262 geographically diverse participants over 13 months (mean age=73 years [SD=5.6]; female: 60%; racial/ethnic minorities: 11%; education ≤12 years: 11%); 92% completed the baseline and at least one follow-up cognitive assessment. Those assigned to active versus placebo CF and MVM were comparably balanced, did not differ in attrition, and demonstrated excellent safety profiles.
For CF, there was no significant difference between active and placebo groups in global cognitive function (p=0.28; difference: z=0.03, 95%CI: -0.02, 0.08). Likewise, CF had no effect on episodic memory (p=0.40; difference: z=0.03, 95%CI: -0.04, 0.09) or on executive function (p=0.23; difference: z=0.03, 95%CI: -0.02, 0.08). In contrast, the MVM group showed a statistically significant improvement in global cognitive function relative to the placebo group (p=0.007; difference: z=0.07, 95%CI: 0.02, 0.12). In addition, the MVM group showed statistically significant improvements relative to placebo in episodic memory (p=0.04; difference: z=0.06, 95%CI: 0.002, 0.13) and executive function (p=0.02; difference: z=0.06, 95%CI: 0.01, 0.11). There was no evidence of an interaction between CF and MVM treatment response. The results of multiple imputation were consistent with results based on observed data.
Conclusion
COSMOS-Mind provides the first evidence from a large-scale, long-term, randomised controlled pragmatic trial in a community-based cohort to support the efficacy of daily MVM use as a safe and readily available intervention to protect cognitive function in older adults. The results of COSMOSMind may have important implications for standard of health care in older adults to protect brain health and possibly prevent cognitive decline associated with AD and related disorders. CF supplementation, however, did not slow cognitive decline.
Medscape article – Multivitamins, but Not Cocoa, Tied to Slowed Brain Aging (Open access)
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