Homocysteine and cognitive function in elderly people

Abstract

Dementia is highly prevalent among elderly people, and projections show that the number of people affected might triple over the next 50 years, mainly because of a large increase in the oldest-old segment of the population. Because of this and the disease's devastating effects, measures for the prevention and early detection of dementia are crucial. Age and years of education are among the most relevant risk factors for dementia, but in recent years the role of homocysteine has also been investigated. Homocysteine is an amino acid produced in the metabolism of methionine, a process dependent on the B vitamins cobalamin, vitamin B6 and folic acid. There is evidence that increased serum homocysteine levels are associated with declining cognitive function and dementia. We review this evidence in addition to the potential mechanisms through which homocysteine acts on the brain to cause cognitive dysfunction, the metabolism of homocysteine and factors associated with alteration of the normal metabolism.

Box 1

Fig. 1: Normal metabolism of homocysteine. Homocysteine is metabolized through 2 pathways: the methionine synthase pathway and the cystathionine pathway. It has been proposed that impaired remethylation of homocysteine produces an increase of intracellular homocysteine that is toxic to neurons, and a decrease in S-adenosyl methionine. Impairment of this reaction would occur in states of cerebral oxidative stress, which would augment oxidation of an intermediate form of vitamin B₁₂ (cob[I]alamin) produced in the methionine synthase reaction and compromise the conversion of the vitamin to its metabolically active form.