MTHFR and Alzheimer disease: The MTHFR 677 T allele codes a thermolabile and less active enzyme, which is associated with decreased folate and increased homocysteine levels.21 Despite its strong metabolic impact, this polymorphism has shown conflicting results in genetic association studies of inflexible cognition,19, 22 major depression1, 23 and other neuropsychiatric disorders, such as Alzheimer's disease (AD),24 bipolar disorder and schizophrenia.23