Table 1.

The role of micronutrients on cognition and their potential mechanisms of action.

Vitamin/Mineral	Clinical Evidence	Possible Mechanisms of Action
B vitamins	Thiamine (vitamin B1) deficiency has been associated with cognitive impairment [266]. Dietary intake of vitamin B6 (pyridoxine) has been associated with better cognitive function [267]. B12 deficiency was shown to impair memory, and serum levels below 300 pmol/L were shown to cause irreversible hippocampus changes [268]. Folic acid (vitamin B9) supplementation was shown to significantly improve cognitive function [269]. Controversial data regarding the role of vitamins B6, B12, and folic acid on cognition have also been reported [270].	B vitamins act as co-enzymes for several catabolic and anabolic enzymatic reactions [271]. They can regulate the levels of homocysteine, and S-adenosylmethionine. They have anti-inflammatory [272] and antioxidant [273] properties.
Vitamin A	Increased cognitive decline was shown to be positively correlated with lower vitamin A levels and marginal vitamin A deficiency was shown to facilitate AD pathogenesis [274]. Vitamin A deficiency can be a predictor of mild cognitive impairment [275]. A higher intake of total carotenoids (which can be converted to vitamin A in the body) was shown to be associated with a decreased risk of moderate or poor cognitive function [276].	Marginal vitamin A deficiency starting in the embryonic period is thought to alter genes associated with AD [277]. Vitamin A can be converted to retinoic acid in the brain, which is essential for synaptic plasticity in regions of the brain involved in learning and memory, such as the hippocampus [278].
Vitamin K	Increased dietary vitamin K intake was to shown to be associated with better cognition in older adults [279,280]. Oral anticoagulants that are non-vitamin K antagonists were shown to be associated with a lower risk of cognitive impairment when compared with vitamin K antagonists or acetylsalicylic acid [281].	Vitamin K is involved in the ɤ-carboxylation of two vitamin K-dependent proteins whose activity contributes to adequate cerebral homeostasis: Gas-6 and protein S. Vitamin K participates as a co-factor in the synthesis of sphingolipids, which are essential constituents of cell membranes [282].
Vitamin D	Maintaining adequate vitamin D status during aging may contribute to a reduction in cognitive decline and a delay in the onset of dementia [283]. Low vitamin D levels were shown to be associated with worse cognitive performance and cognitive decline [284]. Vitamin D deficiency is thought to be a risk factor for AD [285]. The effects of vitamin D supplementation on improving cognition are still controversial [284].	Vitamin D contributes to cerebral activity in both the embryonic and adult brain [286]. Vitamin D regulates calcium homeostasis, clears Aβ peptide deposits, has antioxidant and anti-inflammatory effects, regulates brain plasticity, and improves neurogenesis [287,288,289].
Vitamins C and E	A decrease in mild cognitive impairment was observed in individuals with high plasma vitamin C concentrations [290]. Blood vitamin C concentration was shown to be significantly lower in individuals with dementia when compared with healthy controls [291]. Higher vitamin E levels were shown to be associated with higher scores on verbal memory, immediate recall, and better language/verbal fluency performance, particularly among a younger age group [292]. Controversial data regarding the role of vitamin E on cognition have also been reported [293].	Vitamins C and E are two important exogenous antioxidant molecules, which can decrease oxidative stress, neuroinflammation, and Aβ load [294,295,296].
Selenium	Circulating and brain selenium concentration was shown to be significantly lower in AD patients when compared to healthy controls [297,298].	Selenium has antioxidant properties. Selenoproteins regulate some neurotransmitters, including acetylcholine [299].