Homocysteine levels, genetic background, and cognitive impairment in Parkinson’s disease

Abstract

Background Hyperhomocysteinemia is considered an independent risk factor for cognitive impairment. Objective To study the correlation between homocysteine levels and cognitive impairment in patients with PD. Methods We conducted a case–control study that included 246 patients with PD, of whom 32 were cognitively impaired. The levels of homocysteine, folate, and vitamin B12 were measured in peripheral blood. Multivariate logistic regression analysis was applied to determine differences in homocysteine levels between PD patients with and without cognitive impairment. A meta-analysis was performed to clarify the role of Hcy levels in PD with cognitive decline. Five polymorphisms in genes involved in Hcy metabolism, including MTHFR rs1801133 and rs1801131, COMT rs4680, MTRR rs1801394, and TCN2 rs1801198, were genotyped. Results Our case–control study showed that homocysteine levels were associated with cognitive impairment in PD after adjusting for possible confounding factors such as levodopa equivalent daily dose. The results of our meta-analysis further supported the positive association between homocysteine levels and cognition in PD. We found that the MTHFR rs1801133 TT genotype led to higher homocysteine levels in PD patients, whereas the MTHFR rs1801131 CC genotype resulted in higher folate levels. However, the polymorphisms studied were not associated with cognitive impairment in PD. Conclusions Increased homocysteine levels were a risk factor for cognitive decline in PD. However, no association was found between polymorphisms in genes involved in homocysteine metabolism and cognitive impairment in PD. Large-scale studies of ethnically diverse populations are required to definitively assess the relationship between MTHFR and cognitive impairment in PD.

The severity assessment of Parkinson's disease based on plasma inflammatory factors and third ventricle width by transcranial sonography

“…Homocysteine, uric acid, Cys C, and CRP are implicated in the pathogenesis and progression of degenerative diseases 26–28 . The elevated homocysteine and Cys C levels and lower low‐density lipoprotein cholesterol levels may enhance PD susceptibility 29,30 …”

“…[26][27][28] The elevated homocysteine and Cys C levels and lower low-density lipoprotein cholesterol levels may enhance PD susceptibility. 29,30 Initially, this study performed univariate analysis to screen for factors linked with PD symptom severity. Subsequently, multivariate and lasso logistic regression analyses were conducted to identify inflammatory markers significantly correlated with the PD severity.…”

Controlling the Impact of Helicobacter pylori-Related Hyperhomocysteinemia on Neurodegeneration

“…In PD, hyperhomocysteinemia seems to be connected with cognitive performance and structural damage in the cerebral cortex [ 123 ]. Hyperhomocysteinemia is a risk factor for cognitive decline in PD [ 124 ]. Thus, hyperhomocysteinemia during PD development and progression offers a novel strategy for the diagnosis and treatment of PD [ 122 ].…”

Correlation of Serum High-Sensitivity C-Reactive Protein, Homocysteine, and Macrophage Migration Inhibitory Factor Levels With Symptom Severity and Cognitive Function in Patients With Schizophrenia

“…Hcy is associated with cognitive dysfunction, white matter damage, and dementia, 8 and elevated Hcy is a risk factor for cognitive dysfunction in patients with Parkinson disease. 9 A clinical trial has shown that Hcy reduction with B vitamins significantly slows cognitive dysfunction. 10 Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine and a pluripotent key cytokine involved in immune response and physiological processes.…”

“…Homocysteine (Hcy) is a nonprotein amino acid containing sulfhydryl derived from methionine and is a homolog of cysteine. Hcy is associated with cognitive dysfunction, white matter damage, and dementia, 8 and elevated Hcy is a risk factor for cognitive dysfunction in patients with Parkinson disease 9 . A clinical trial has shown that Hcy reduction with B vitamins significantly slows cognitive dysfunction 10 .…”