Homocysteine in relation to cognitive performance in pathological and non-pathological conditions

Abstract

Elevated serum homocysteine has been associated with increased risk of Alzheimer's disease. Furthermore, elevated homocysteine levels are related to cognitive dysfunction in the elderly. The aim of the present study was to explore the disease specificity of the relation between serum total homocysteine levels and cognitive function. For this, we summarize data from several studies on homocysteine levels in both normal and pathological conditions performed in our laboratories and evaluate possible mechanisms of effects of elevated homocysteine levels in the central nervous system. Total homocysteine levels were measured in serum of: 1) healthy aging individuals; 2) patients with Alzheimer's and Parkinson's disease and patients with other cognitive disorders; and 3) patients with multiple sclerosis. Increased serum homocysteine concentration was related to worse cognitive performance over a 6-year period in the normal aging population (r=-0.36 to -0.14, p<0.01 for the Word learning tests; r=0.76, p<0.05 for the Stroop Colored Word test). Homocysteine was only increased in patients with Parkinson's disease on L-Dopa therapy (18.9 vs. 16.5 micromol/L in healthy controls), and not in dementia patients. Homocysteine was elevated in patients with progressive multiple sclerosis (15.0 micromol/L, n=39, compared to 12.0 micromol/L in 45 controls) and correlated to both cognitive and motor function (r=-0.33 and -0.33, p<0.05, respectively). The relationship between homocysteine and cognitive function in non-pathological and pathological situations indicates that changes in its levels may play a role in cognitive functioning in a broad spectrum of conditions.

Interactive effects of COMT Val108/158Met and MTHFR C677T on executive function in schizophrenia

“…However, given the detrimental effects of the T allele on executive function measures, this second putative interaction may be less salient to perseveration. It is also possible that the statistical interaction between COMT and MTHFR does not reflect a synergistic biochemical effect per se, but rather independent cumulative effects on prefrontal function (e.g., COMT via its impact on dopamine, and MTHFR via an effect on homocysteine, which has also been negatively associated with cognitive function) [Teunissen et al, 2005]. Additional work examining biochemical and neural interactions of the COMT and MTHFR polymorphisms will be necessary to validate their joint effects on frontal lobe physiology.…”

Homocysteine, Folate and Cognition in a Large Community-Based Sample of Elderly People – The 3C Dijon Study

“…More recently, there is growing evidence for elevated plasmatic homocysteine concentration to be a risk factor for poor cognitive performances [3][4][5][6][7][8][9][10][11][12] as well as dementia [11] in crosssectional and longitudinal studies [3,[13][14][15][16] .…”

Extracellular transsulfuration generates hydrogen sulfide from homocysteine and protects endothelium from redox stress

“…33 and 41) and accelerates the progression of atherosclerosis (10). Hcy increases blood-brain barrier permeability (12,17) and is a risk factor for neurodegenerative disease (25,34,35), especially Alzheimer disease (AD) (6,19,31). Even mildly elevated Hcy (Ͼ14 mol/l) creates a twofold increase in risk of AD with a significant correlation between blood Hcy concentration and cognitive impairment (8,31).…”