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Ageing Res Rev. 2015 Jul;22:9-19. doi: 10.1016/j.arr.2015.04.005. Epub 2015 May 2.

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

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Institut Pasteur, INSERM U1202, Unité de Pathogénie Microbienne Moléculaire, 75015 Paris, France. Electronic address:
Department of Biochemistry, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.
Faculty of Nutrition and Food Sciences, University of Porto, 4200-465 Porto, Portugal.
Health Service of Autonomous Region of Madeira (SESARAM), Madeira, Portugal.
Institut Pasteur, INSERM U1202, Unité de Pathogénie Microbienne Moléculaire, 75015 Paris, France; Center for Biotechnology and Fine Chemistry, School of Biotechnology, Portuguese Catholic University, 4200-702 Porto, Portugal.


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.


Aging; B-vitamin supplements; Dementia; Depression; Folate; Homocysteine

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