ROLE OF HOMOCYSTEINE IN AGE-RELATED VASCULAR AND NONVASCULAR DISEASES

Homocysteine (Hey) may represent a metabolic link in the pathogenesis of atherosclerotic vascular diseases and old-age dementias. Hyperhomoc ysteinemia is an independent risk factor for coronary artery disease a nd peripheral vascular disease, and is also associated with cerebrovas cular disease; specifically, the risk of extracranial carotid atherosc lerosis significantly increases in relation to Hey levels. Hey is a re liable marker of vitamin B12 deficiency, a common condition in the eld erly which is known to induce neurological deficits including cognitiv e impairment; a high prevalence of folate deficiency has been reported in psychogeriatric patients suffering from depression and dementia. B oth these vitamins occupy a key position in the remethylation and synt hesis of S-adenosylmethionine (SAMe), a major methyl donor in CNS; the refore, deficiencies in either of these vitamins lead to a decrease in SAMe and increase in Hcy, which can be critical in the aging brain. A nother pathogenetic mechanism linking high Hey levels to reduced cogni tive performances in the elderly might be represented by excitotoxicit y, since hyperhomocysteinemia may lead to an excessive production of h omocysteic acid and cysteine sulphinic acid, which act as endogenous a gonists of NMDA receptors. Considering the reasonably high prevalence in the general population of a genetic predisposition to a thermolabil e form of the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), hyperhomocysteinemia can be seen as the result of multiple genetic an d environmental factors leading to vascular and/or neurodegenerative d isorders where age-related involutive phenomena represent a common pat hogenetic ground. Systematic studies in different psychogeriatric cond itions monitoring Hey levels and clinical features before and after vi tamin supplementation are therefore highly recommended. (C) 1997, Edit rice Kurtis.