Biomarkers are a promising approach to the prediction and early intervention of Alzheimer\u27s disease. We demonstrated that cortical functional MRI (fMRI) activation during a semantic memory task and apolipoprotein-E ?4 allele inheritance (APOE?4) effectively predicted cognitive decline after 18-months in healthy, asymptomatic elders. Hippocampal volume added modest prediction, while AD family history and demographics were ineffective. Previous studies have linked plasma homocysteine (tHcy), vitamin B12 and creatinine values to cognitive funcitoning, cortical atrophy, hippocampal atrophy and neuropathology, and vascular integrity. Here we incorporated total plasma homocysteine (tHcy), B12 creatinine values into our previous predictive models. Of 78 healthy elders, 27 (34.6%) exhibited significant cognitive decline after 18-months. tHcy, but not B12 or creatinine, was marginally positively correlated with cortical semantic memory fMRI activation, particularly in stable participants. Logistic regression showed that tHcy, when added to APOE?4 and cortical fMRI, was a significant predictor of outcome and strengthed the already significant model (p = .007; C = .80 and R2 = .37). However, control for B12 and creatinine covariates diminished tHcy as a predictor (p = .084), though the model was still stronger than without this factor (C = .78 and R = 31). tHcy did not significantly interact with APOE?4, as has previously been reported. Neither B12 nor creatinine was similarly effective as a predictor. These results suggest that commonly investigated blood serum biomarkers are at best weakly associated with predicting age- and dementia-related cognitive decline in healthy, asymptomatic elders. fMRI and APOE?4 presently provided the best predictive model
