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

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 withMTAtotal score inAD(r = 0.448, p < 0.001). VitaminB12 levels were positively correlated withMoCAinVaD(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.

Automated summary

This study investigates the changes of homocysteine, vitamin B12, and folate levels in different subtypes of dementia and their associations with cognitive function and MRI markers. The results show that elevated homocysteine levels and lower vitamin B12 levels are associated with various types of dementia. Homocysteine levels are correlated with temporal lobe atrophy in Alzheimer's disease, while vitamin B12 levels are associated with general cognition in vascular dementia. Hyperhomocysteinemia may increase the risk of Alzheimer's disease, vascular dementia, and frontotemporal dementia.