Cognitive impairment is associated with elevated serum homocysteine levels among older adults

Eur J Nutr. 2019 Feb;58(1):399-408. doi: 10.1007/s00394-017-1604-y. Epub 2018 Jan 10.


Purpose: The aim of this study was to examine the associations between the risk of cognitive impairment and the serum levels of folate, vitamin B12, and homocysteine (Hcy).

Methods: Subjects were persons aged 60-79 years who participated in the Yangpyeong Cohort study between 2011 and 2012. Cognitive impairment and normal subjects consisted of 100 pairs of old adults matched by age, sex, and education levels. Cognitive function was evaluated with the Korean version of the Mini-Mental State Examination for Dementia Screening (MMSE-DS). Pearson's partial correlation coefficients and conditional multiple logistic regression analysis were applied to determine the associations between cognitive function and the serum levels of folate, vitamin B12, and Hcy.

Results: Compared with the matched normal group, the cognitive impairment group had higher proportions of folate deficiency (< 3 ng/mL) and hyperhomocysteinemia (≥ 15 µmol/L). Serum Hcy concentrations were inversely associated with serum folate (r = - 0.234, p = 0.001) and MMSE-DS score (r = - 0.150, p = 0.037) after adjusting for age, sex, and education. The high Hcy group showed a higher prevalence of cognitive impairment (4th vs. 1st quartile, OR 3.30, 95% CI 1.12-9.72, p for trend = 0.014) after adjusting for exercise.

Conclusions: The present findings suggest a putative protective role of high serum folate and normal Hcy against cognitive impairment among older adults.

Keywords: Cognitive impairment; Folate; Homocysteine; Vitamin B12.

MeSH terms

  • Aged
  • Causality
  • Cognitive Dysfunction / blood*
  • Cognitive Dysfunction / epidemiology*
  • Cohort Studies
  • Comorbidity
  • Female
  • Folic Acid / blood
  • Folic Acid Deficiency / blood*
  • Folic Acid Deficiency / epidemiology*
  • Homocysteine / blood*
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Prevalence
  • Republic of Korea / epidemiology
  • Vitamin B 12 / blood


  • Homocysteine
  • Folic Acid
  • Vitamin B 12