Folate, Cognition, and Depression in the Era of Folic Acid Fortification

Abstract

ABSTRACT: It has long been recognized that folate deficiency is associated with impaired cognitive function, particularly in older adults. Moreover, folate deficiency contributes to the symptoms of clinical depression and negatively influences the efficacy of antidepressant medications. The pathophysiological mechanisms by which folate deficiency influences cognition and depressive mood are not clearly understood, but may be mediated by decreased intracellular concentration of the methyl donor S‐adenosylmethionine in the brain and increased concentration of the putative vascular toxin homocysteine in the blood (hyperhomocysteinemia). Folic acid fortification of flour in the United States, intended to reduce the risk of neural tube defects, has been in effect since January 1, 1998. The program has proven to be highly successful having lowered the prevalence of folate deficiency and hyperhomocysteinemia, as well as the incidence of neural tube defects. An important question is whether associations between folate status, cognition, and depression remain significant. In this presentation, the evidence supporting the relationships between folate status, cognition, and depression will be summarized. In addition, epidemiological data will be presented from the Sacramento Area Latino Study on Aging (SALSA), a community‐based cohort study of physical and cognitive function in Latino Americans age 60 years and older, that indicate folate status remains a significant determinant of cognitive function and depressive mood despite the success of folic acid fortification.