Vitamin B12-B6-folate treatment improves blood-brain barrier function in patients with hyperhomocysteinaemia and mild cognitive impairment

Dement Geriatr Cogn Disord. 2003;16(3):145-50. doi: 10.1159/000071002.


Thirty patients had mild cognitive impairment and increased homocysteine levels in serum. On average, they were supplemented orally with a high dose of a vitamin B12-B6-folate combination for 270 days. All patients had normal serum B12 and folate levels at baseline. Cerebrospinal fluid levels of the tau protein (CSF-tau) and the albumin ratio were measured before and after treatment. The serum homocysteine levels were normalised after treatment. The albumin ratio significantly correlated with vascular risk factors. At baseline, the ratio was higher in the patients in comparison with age-matched controls. After treatment, the ratio was significantly reduced, which may indicate a tightening of the blood-brain barrier. The CSF-tau levels did not change significantly although there was a numeric decline. None of the patients progressed into dementia during the treatment period. When treated with a vitamin B12-B6-folate combination, patients with mild cognitive impairment and hyperhomocysteinaemia appear to improve their blood-brain barrier function. They may also stabilise their cognitive status. Further investigations are warranted on the role of blood-brain barrier dysfunction in the pathogenesis of dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blood-Brain Barrier / drug effects*
  • Cognition Disorders / complications*
  • Drug Therapy, Combination
  • Female
  • Folic Acid / administration & dosage*
  • Humans
  • Hyperhomocysteinemia / complications
  • Hyperhomocysteinemia / drug therapy*
  • Hyperhomocysteinemia / physiopathology*
  • Male
  • Middle Aged
  • Regression Analysis
  • Serum Albumin / cerebrospinal fluid
  • Serum Albumin / metabolism
  • Vitamin B 12 / administration & dosage*
  • Vitamin B 6 / administration & dosage*


  • Serum Albumin
  • Vitamin B 6
  • Folic Acid
  • Vitamin B 12