Serum homocysteine: Interplay with other circulating and genetic factors in association to Alzheimer's type dementia

Objectives: To study the interplay between serum concentrations of homocysteine, steroid hormones and vitamins B and mutations in 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, in association to Alzheimer's type dementia (ATD). Design and methods: Case-control study including 19 individuals diagnosed with ATD and 36 healthy controls. Serum concentrations of the analytes were determined and MTHFR 1298A → C mutation was screened by PCR-RFLP. Results: Multivariable logistic regression analysis identified homocysteine (OR = 1.92, P < 0.01), cholesterol (OR = 1.14, P < 0.001), estradiol (OR = 0.728, P < 0.001), uric acid (OR = 2.42, P < 0.02), vitamin B₁₂ (OR = 0.984, P < 0.004) and MTHFR 1298A → C mutation (OR = 6.01, P < 0.04) as independent predictors of ATD. Positive interaction between homocysteine and uric acid, creatinine, urea or cortisol (P < 0.02) and negative interaction between homocysteine and vitamin B₁₂ or MTHFR 1298A → C mutation (P < 0.03) were observed. Conclusions: High serum concentrations of homocysteine, cholesterol and uric acid, and low concentrations of estradiol and vitamin B₁₂, as well as the MTHFR 1298A → C mutation are simultaneously associated to ATD.