Homocysteine, B-vitamin status and cognitive decline

Nutrition Research Newsletter, August, 2004

In recent years, evidence has shown an association between Alzheimer disease (AD) and indicators et atherosclerosis or presence of brain infarcts. This has brought into question the direct or additional contribution of cerebrovascular abnormalities and lesions to cognitive impairment and the pathogenesis and progression of AD. Elevated total homocysteine concentrations were first found in the pathogenesis of arteriosclerosis in 1969. Recent research has reported significant, independent associations between elevated total homocysteine concentrations and ischemic heart disease or stroke. However, whether hyperhomocysteinemia is a risk factor for vascular disease or a consequence of tissue damage or repair is unknown.

Homocysteine is a sulfur-containing amino acid produced by the demethylation of dietary methionine. Homocysteine is recycled back into methionine through a pathway that involves vitamin B-12 and folate. Therefore, a recent study set out to examine the associations of plasma total homocysteine, serum folate, and vitamin B-12 concentrations with mild cognitive impairment, AD, and vascular dementia (VaD), independently of other vascular and nonvascular risk factors.

The study included 228 subjects at a memory clinic in Switzerland. The subjects were divided into three groups, according to clinical diagnosis. Group 1 included 55 elderly control subjects free of cognitive impairment; group 2 included 81 mildly cognitively impaired subjects; and group 3 consisted of 92 demented patients. Disease stage was rated by means of the Clinical Dementia Rating (CDR) scale, whereas the Mini-Mental State Examination (MMSE)--a brief cognitive test used in clinical practice--was administered to grade the subjects' global cognitive impairment. Blood was collected and analyzed for total homocysteine concentrations, as well as for folate and vitamin B-12.

Subjects in the lowest folate tertile had significantly higher adjusted odds ratios (ORs) for mild cognitive impairment (OR 3.1; 95% CI: 1.2, 8.1) and dementia (3.8; 1.3, 11.2). Hyperhomocysteinemia was significantly associated with dementia (adjusted OR: 4.3; 1.3, 14.7) and AD (adjusted OR: 3.7; 1.1, 13.1). In subjects with a CDR of 0.5, the mean ([ or -] SE) MMSE score was significantly lower (P<0.05) in the highest homocysteine tertile (24.5 [ or -] 0.5) than in the lowest tertile (26.6 [ or -] 0.5).

These results suggest that folate deficiency may come before AD and VaD onset. Hyperhomocysteinemia may also be an early risk factor for cognitive decline in elderly individuals, but further research is needed to address its role in dementia.

P. Quadri, C. Fragiacomo, R. Pezzati, et al. Homocysteine, folate, and vitamin B-12 in mild cognitive impairment, Alzheimer disease, and vascular dementia. Am J Clin Nutr;80:114-122 (July, 2004). [Correspondence: P Quadri, Geriatric Division, Ospedale Regionale della Beata Vergine, Via Turconi 23, 6850 Mendrisio-Switzerland. E-mail: peirluigi.quadri@bluewin.ch].