Plasma Homocysteine and Serum Folate and Vitamin B12 Levels in Mild Cognitive Impairment and Alzheimer's Disease: A Case-Control Study

Nutrients. 2017 Jul 8;9(7):725. doi: 10.3390/nu9070725.


Homocysteine (Hcy) is a risk factor for brain atrophy, cognitive impairment, and dementia. Vitamin B12 and folate are cofactors necessary for the methylation of Hcy. However, there is some debate regarding the differing levels of plasma Hcy and serum folate and vitamin B12 among healthy controls, patients with mild cognitive impairment (MCI), and patients with Alzheimer's disease (AD). This study aimed to evaluate how the levels of plasma Hcy and its biological determinants, folate and vitamin B12, are related to MCI and AD in older Chinese adults. This is a case-control study including 112 subjects with MCI, 89 AD patients and 115 healthy controls. Diagnosis of AD was made according to the NINCDS-ADRDA and MCI with modified Petersen's criteria. Serum folate and vitamin B12 concentrations were analyzed by radioimmunoassay, and plasma Hcy was assessed by a high-performance liquid chromatography-fluorescence method. Multivariate analysis of regression was used to examine the odds ratio (OR) of MCI or AD with Hcy or vitamin levels. Results have shown that serum folate and vitamin B12 levels were significantly lower, but the plasma Hcy level was higher, in patients with MCI and AD than in healthy controls. Multivariate regression analyses showed that subjects in the lowest folate tertile had significantly higher adjusted ORs for MCI (OR: 3.07; 95% confidence interval [CI]: 1.12, 8.07) and AD (3.42; 95% CI: 1.15, 8.34) compared to subjects in the highest tertile. The highest Hcy tertile was significantly associated with MCI (adjusted OR: 2.81; 95% CI: 1.15, 4.73) and AD (adjusted OR: 3.64; 95% CI: 1.13, 9.04) compared to the lowest tertile. No association existed between low vitamin B12 levels and AD or MCI (p > 0.05). Low blood levels of folate and vitamin B12 and elevated Hcy levels were associated with MCI and AD in older Chinese adults, and the association was stronger for AD.

Keywords: Alzheimer’s disease; case-control study; folate; homocysteine; mild cognitive impairment.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Case-Control Studies
  • Cognitive Dysfunction / blood*
  • Female
  • Folic Acid / blood*
  • Homocysteine / blood*
  • Humans
  • Male
  • Odds Ratio
  • Psychiatric Status Rating Scales
  • Risk Factors
  • Vitamin B 12 / blood*


  • Homocysteine
  • Folic Acid
  • Vitamin B 12