Homocysteine Modulates Brain Functional Connectivity in a Memory Retrieval Task

Abstract

Background: Homocysteine, a methionine metabolite, is a recognized risk factor for accelerated age-related cognitive decline and dementia. Objective: In the light of studies indicating increases in brain activity and brain functional connectivity in the early stages of age-related cognitive decline, we undertook a study to examine the relationship between plasma homocysteine levels and brain functional connectivity in a group of late middle-aged males at risk of cognitive decline due to high body mass index and a sedentary lifestyle. Methods: Brain functional connectivity was measured using the steady state visual evoked potential event related partial coherence while 38 participants performed a memory task where each trial comprised an object recognition task followed by a location memory task. Results: We observed a significant transient peak in the correlation between plasma homocysteine levels and fronto-parietal brain functional connectivity immediately before the presentation of the memory location component of the task. Significantly, this correlation was only apparent if the participant pool included individuals with homocysteine concentrations above 11μmole/L. Conclusion: Our findings suggest that the increased brain functional connectivity observed in the earlier stages of age-related cognitive decline reflects pathognomonic changes in brain function and not compensatory changes engaged to enhance task performance. Our findings also suggest that homocysteine interferes with the inhibition of cortical networks where this inhibition is necessary for optimum task performance. Finally, we observed that the effect of homocysteine on brain functional connectivity is only apparent at concentrations above 11μmol/L.