Folates and aging: Role in mild cognitive impairment, dementia and depression

• Folate deficiency is prevalent in older individuals due to intestinal malabsorption.
• Onset and progression of cognitive disorders is associated with a low folate status.
• Hyperhomocysteinemia is the most important mechanism underlying this association.
• It is unclear if folate supplementation improves cognition in older individuals.

In almost all tissues, including the brain, folates are required for one-carbon transfer reactions, which are essential for the synthesis of DNA and RNA nucleotides, the metabolism of amino acids and the occurrence of methylation reactions. The aim of this paper is to review the impact of folate status on the risk of development of neuropsychiatric disorders in older individuals. The prevalence of folate deficiency is high among individuals aged ≥65 years mainly due to reduced dietary intake and intestinal malabsorption. Population-based studies have demonstrated that a low folate status is associated with mild cognitive impairment, dementia (particularly Alzheimer’s disease) and depression in healthy and neuropsychiatric diseased older individuals. The proposed mechanisms underlying that association include hyperhomocysteinemia, lower methylation reactions and tetrahydrobiopterin levels, and excessive misincorporation of uracil into DNA. However, currently, there is no consistent evidence demonstrating that folic acid supplementation improves cognitive function or slows cognitive decline in healthy or cognitively impaired older individuals. In conclusion, folate deficiency seems to be an important contributor for the onset and progression of neuropsychiatric diseases in the geriatric population but additional studies are needed in order to increase the knowledge of this promising, but still largely unexplored, area of research.