Brain Hemodynamic Intermediate Phenotype Links Vitamin B₁₂ to Cognitive Profile of Healthy and Mild Cognitive Impaired Subjects

Figure 1

The two alternative hypotheses for the relationship between blood biochemistry, brain activity, and cognitive profiles. (a) Scheme depicting the potential role of B₁₂, folate, tHcy, and their interactions as direct predictors of distinct cognitive profiles. These profiles are represented by principal components (PC) derived from subjects’ scores at seventeen neuropsychological tests. Age, years of education, Mini Mental State Examination scores and fMRI task accuracy are included in the model as nuisance variables. (b) Alternatively, brain hemodynamic activity can act as an intermediate phenotype in linking blood biochemistry to subjects’ cognitive profiles. First, brain regions modulated by B₁₂, folate, tHcy, and their interactions are identified and hemodynamic activity is subsequently used as a predictor of cognitive profiles. The same nuisance variables are included in the model at both steps of analysis. tHcy: homocysteine; Fol: folate; MMSE: Mini Mental State Examination.

(a)

(b)