A number of prospective studies have suggested that elevated serum total homocysteine (tHcy), and low folate and vitamin B12 levels are a risk factor for Alzheimer’s disease (Clarke et al. Arch Neurol 1998; 55: 1449-1455). In the Prospective Population Study of Women in Gothenburg, elevated tHcy in midlife was associated with a hazard ratio of 2.1 for developing AD and 2.4 for AD with no cerebrovascular disease (Zylberstein et al. Neurobiol Aging 2011; 32: 380-386). B vitamins (folate, B6, B12) are cofactors or substrates for enzymes in homocysteine metabolism.
Expert recommendations for determining tHcy levels and assessing risk of cognitive impairment were published in 2004 (Refsum et al. Clin Chem 2004; 50: 3-32; free full text at www.clinchem.org/cgi/content/full/50/1/3).