Serum Homocysteine, Vitamin B12, Folate, and Their Association with Mild Cognitive Impairment and Subtypes of Dementia

J Alzheimers Dis. 2022;90(2):681-691. doi: 10.3233/JAD-220410.

Abstract

Background: Although elevated levels of homocysteine (Hcy) are associated with cognitive impairment and dementia, the relevance of Hcy, vitamin B12, and folate levels to subtypes of dementia are still unknown.

Objective: To investigate the changes of Hcy, vitamin B12, and folate levels in mild cognitive impairment (MCI) and subtypes of dementia including Alzheimer's disease (AD), vascular dementia (VaD), frontotemporal dementia (FTD), and Lewy body dementia (LBD), and their relationships with cognitive function and magnetic resonance imaging (MRI) markers.

Methods: We measured serum levels of Hcy, vitamin B12, and folate in 257 subjects. Each subject underwent cognitive function assessment and brain MRI test. The Fazekas and temporal lobe atrophy (MTA) visual rating scales were used to assess the degree of white matter hyperintensities and MTA, respectively.

Results: Serum levels of Hcy was higher and vitamin B12 was lower in AD, VaD, FTD, and LBD groups than cognitively normal controls. No significant differences of folate levels were found among 6 groups. Hcy levels were positively correlated with MTA total score in AD (r = 0.448, p < 0.001). Vitamin B12 levels were positively correlated with MoCA in VaD (r = 0.497), and negatively correlated with MTA total score in AD (r = - 0.325) (ps < 0.05). Hyperhomocysteinemia may increase the risk of AD (OR = 2.744), VaD (OR = 3.600), and FTD (OR = 3.244) in the adjusted model (ps < 0.05).

Conclusion: Hcy and vitamin B12 levels are associated with MTA in AD. Vitamin B12 levels are associated with general cognition in VaD. Hyperhomocysteinemia is a risk factor for not only AD and VaD but also FTD.

Keywords: Alzheimer’s disease; B vitamin; Lewy body dementia; dementia; frontotemporal dementia; homocysteine; mild cognitive impairment; vascular dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / complications
  • Cognitive Dysfunction*
  • Dementia, Vascular*
  • Folic Acid
  • Frontotemporal Dementia* / complications
  • Homocysteine
  • Humans
  • Hyperhomocysteinemia*
  • Vitamin B 12

Substances

  • Folic Acid
  • Homocysteine
  • Vitamin B 12