There are two common polymorphic genetic variants of the MTHFR gene that can lead to impaired functioning of the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine, leading to hyperhomocysteinemia, which is a risk factor for dementia owing to an associated BBB dysfunction and subsequent small-vessel disease pathology [93]. This evidence concerns the gene MTHFR and hyperhomocysteinemia.