Geriatric psychiatry: Is the jury still out on the cognitive effects of homocysteine and one-carbon metabolism?

Purpose of review: This review considers the evidence for the contribution of hyperhomocysteinemia to cognitive impairment, the dementias and Parkinson's disease, focusing on published literature from April 2002 to April 2003. Recent findings: Homocysteine is a sulphur-containing amino acid that is involved in cycles related to one-carbon metabolism within the body, and elevations in its level can result from multiple aspects of these cycles. Elevated homocysteine impairs methylation, crucial to DNA synthesis and repair, is toxic to the vascular system, is cytotoxic and is directly neurotoxic. These effects interact with ageing-related pathology and toxins to augment neurodegenerative processes. Controversies remain in the ascertainment of homocysteine levels and in the salience of its contribution to cognitive impairment, the dementias and Parkinson's disease. However, cross-sectional studies generally agree homocysteine levels greater than 14 μmol/l are associated with increased risk of cognitive impairment. Hyperhomocysteinemia is associated with an increased risk of cognitive impairment after stroke, and is a contributory factor to the cognitive deficits of vascular dementia and AD. Elevated homocysteine levels have been demonstrated in L-dopa treated Parkinson's disease patients in associated with vascular risk. Hyperhomocysteinemia is also associated with increased brain atrophy in healthy elderly. Summary: There is an increasingly solid case for the association between hyperhomocysteinemia, as a marker of disturbed one-carbon metabolism, and cognitive impairment. The findings from preliminary investigations of vitamin supplementation to lower homocysteine in candidate conditions such as stroke and dementia are encouraging, but evidence is needed from large randomized controlled trials before supplementation can be advocated.