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Association analysis between circulating methylmalonic acid and cognitive performance: a population-based

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Elevated methylmalonic acid (MMA) levels are linked to poorer cognitive function in older adults. Homocysteine, hypertension, and chronic kidney disease significantly influence this association.

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Gerontology

Background:

  • Cognitive impairment is a common neurological issue, often linked to nervous system dysfunction.
  • Methylmalonic acid (MMA), a biomarker for vitamin B12 (B12) status, plays a role in propionate metabolism.
  • The precise relationship between MMA and cognitive performance remains incompletely understood.

Purpose of the Study:

  • To investigate the correlation between circulating MMA levels and cognitive performance in a large, population-based cohort.
  • To explore potential confounding factors influencing the MMA-cognition relationship.

Main Methods:

  • A cross-sectional study analyzed data from 4,464 adults aged 60+ from the NHANES (1999-2014).
  • Cognitive function was assessed using the Digit Symbol Substitution Test (DSST).
  • Statistical analyses included correlation, regression models, and restricted cubic splines to evaluate associations, controlling for numerous covariates.

Main Results:

  • A significant negative correlation was observed between serum MMA levels and cognitive scores (ρ = -0.12, p < 0.001).
  • This negative association persisted after adjusting for covariates in multiple linear regression models (B = -0.13 to -0.14).
  • Sensitivity analyses revealed the association was attenuated by homocysteine (HCY) and removing participants with hypertension or chronic kidney disease (CKD).

Conclusions:

  • Circulating MMA is negatively correlated with cognitive function in individuals aged 60 and above.
  • Homocysteine, hypertension, and chronic kidney disease are identified as significant factors modulating this relationship.