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Association Between Serum Methylmalonic Acid and Poor Cognitive Performance
Ziping Wang1, Yan Deng2, Liangkai Chen3
1Department of Nutrition, Hygiene and Toxicology (ZW, BL, TW, SR), Academy of Nutrition and Health, School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, China.
Objective:
Methylmalonic acid (MMA) accumulation, as a novel link between aging and cancer progression, had attracted widespread attention. However, there was limited evidence focusing on its association with age-related cognitive decline in elderly people. Further evidence for this will help provide new perspective on preventing cognitive disorders such as dementia.
Methods:
Overall, 2,760 older adults (mean age: 69.46 years, female: 50.98%) from the National Health and Nutrition Examination Survey were included. Serum MMA concentrations were measured by gas chromatography/mass spectrophotometry. Four cognitive domains (immediate memory, delayed memory, language function, attention) were evaluated through a battery of neuropsychological tests. The global cognition was assessed by a composite z score. And the subjective cognitive decline was examined via self-reports. The weighted linear regression and logistic regression model were performed to evaluate the relationship of MMA with cognition.
Results:
Individuals with higher MMA levels tended to have poorer cognitive function, especially in the language function and attention domain. In the logistic regression model, compared to participants with MMA <170 nmol/L, those with MMA ≥250 nmol/L have the ORs (95% confidence interval) of 1.53 (1.15, 2.04) for poor global cognition, 1.56 (1.09, 2.23) for language function, and 1.48 (1.02, 2.15) for attention. In the multivariable linear regression model, the β coefficients (95% confidence intervals) of MMA were -1.84 (-3.44, -0.25) for global cognitive score and -2.06 (-3.38, -0.74) for attention.
Conclusion:
The circulating MMA was inversely associated with global cognition, language function, and attention in older adults. The underlying causality and biological mechanisms warrant further exploration.
Insights
Higher methylmalonic acid (MMA) levels are linked to poorer cognitive function in older adults, particularly affecting language and attention. This finding may offer new insights into preventing age-related cognitive decline.
Area of Science:
- Gerontology
- Neuroscience
- Biochemistry
Background:
- Methylmalonic acid (MMA) accumulation is increasingly recognized for its role in aging and cancer.
- Limited research exists on the association between MMA and age-related cognitive decline in the elderly.
- Understanding this link may inform strategies for preventing cognitive disorders like dementia.
Purpose of the Study:
- To investigate the association between serum methylmalonic acid (MMA) levels and cognitive function in older adults.
- To explore the relationship between MMA and specific cognitive domains, including memory, language, and attention.
- To provide evidence for the potential role of MMA in age-related cognitive decline.
Main Methods:
- Analysis of data from 2,760 older adults from the National Health and Nutrition Examination Survey.
- Measurement of serum MMA concentrations using gas chromatography/mass spectrophotometry.
- Assessment of cognitive function through neuropsychological tests evaluating immediate memory, delayed memory, language, and attention, alongside global cognition and self-reported subjective cognitive decline.
- Application of weighted linear and logistic regression models to determine the association between MMA and cognitive outcomes.
Main Results:
- Higher MMA levels were associated with poorer cognitive function, notably in language and attention domains.
- Logistic regression indicated that individuals with MMA ≥250 nmol/L had increased odds of poor global cognition (OR: 1.53), language function (OR: 1.56), and attention (OR: 1.48) compared to those with MMA <170 nmol/L.
- Multivariable linear regression revealed a significant inverse association between MMA and global cognitive score (β: -1.84) and attention (β: -2.06).
Conclusions:
- Circulating methylmalonic acid (MMA) is inversely associated with global cognition, language function, and attention in the elderly population.
- Further research is warranted to elucidate the causal relationships and underlying biological mechanisms connecting MMA and cognitive function.
- These findings highlight MMA as a potential biomarker for age-related cognitive decline.
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