Hyperhomocysteinemia is associated with cognitive impairment in multiple sclerosis

Abstract

Hyperhomocysteinemia (HHcy) has been associated with cognitive impairment in various neurological diseases. Cognitive impairment occurs early in multiple sclerosis (MS). Conflicting data have been reported regarding plasma total homocysteine (tHcy) levels in MS patients, and the impact of HHcy on cognitive impairment in MS is not known. This study investigated whether plasma total homocysteine levels are increased in MS and if HHcy is associated with cognitive impairment in MS. We compared tHcy levels in 94 patients with MS and 53 healthy age-matched controls. We used a neuropsychological test battery that included the Raven's Coloured Progressive Matrices, the Visual Search Test, the Trail Making Test A and B, the Immediate and Delayed Recall of a Short Story, the 30 Paired Word Associates, the Rey-Osterrieth Complex Figure Test, and the Semantic and Verbal Fluency Tests. Clinical (sex, age, type of MS, relapse, disease duration, coexisting disease, smoking habit, and physical disability) and laboratory variables (HHcy, low serum levels of folate and vit.B12, MTHFR genotype) were evaluated for their ability to predict cognitive impairment. The mean tHcy was higher in patients (13.19 micromol/L, SD5.58) than in controls (9.81 micromol/L, SD2.53; p < 0.001). Univariate analysis determined the following factors to be associated with cognitive impairment: higher age at observation, chronic progressive course of disease, longer disease duration,moderate or severe physical disability, and frequency of HHcy. With multivariate regression analysis, there remained a significant association only between frequency of HHcy and cognitive impairment (beta 0.262, p = 0.01). We conclude that tHcy levels are increased in MS and that HHcy is associated with cognitive impairment in this disease.

Risk of Arterial Cardiovascular Diseases in Patients with Multiple Sclerosis: A Population-Based Cohort Study

“…Immobilization and lack of physical activity among patients with MS may also increase the risk of CVD. There is evidence that homocysteine plasma levels, a risk factor for CVD, may be higher in patients with MS [42][43][44] . Thrombogenic factors [26,42,45] and endothelial function [47] may also be altered in patients with MS. As mentioned, MS patients may have a healthier lifestyle after MS diagnosis, and cardiovascular risk factors may be identified and treated during frequent health care contacts, which may explain the attenuated cardiovascular risk during follow-up.…”

Homocysteine Metabolism, Atherosclerosis, and Diseases of Aging

“…These results support excitotoxicity induced by homocysteine as an important factor in the apoptosis observed in atherogenesis and the neuronal necrosis observed in neurodegenerative diseases, including dementia (278), schizophrenia (148), cognitive decline (211), and multiple sclerosis (268). These results help to explain the mental retardation observed in homocystinuria caused by cystathionine synthase deficiency (215) and the degeneration of grey and white matter of brain observed in methionine synthase deficiency (175).…”

Homocysteine and Cognitive Impairment

“…Elevated tHcy has been shown to be associated with hippocampal atrophy [66,67] and with cognitive decline in the absence of cerebrovascular disease [8,68] . Elevated tHcy has also been shown to be associated with cognitive impairment in patients with multiple sclerosis [69] . A nonvascular mechanism is also supported by the positive association found between tHcy and plasma amyloid-␤ levels that suggests that these factors can interact to potentiate neurodegeneration [37] .…”