Homocysteine folate and incidence of dementia

Nutrition Research Newsletter, Oct, 2005

In Western societies, the prevalence of Alzheimer's disease (AD) is increasing with the increased number of elders in the population. Therefore, it is important to identify modifiable risk factors for this disease. Homocysteine (Hcy) is a unique candidate for this role because of its direct neurotoxicity and its association with cerebrovascular disease, which is currently believed to play a significant role in AD etiology. In addition, some studies have already shown an association between AD and elevated total homocysteine (tHcy) concentrations. However, only two longitudinal studies have investigated this relationship and their results were inconsistent. Therefore, a group of Italian researchers investigated the relationship between high-plasma tHcy concentrations and risk of dementia and AD in an elderly population.

A cohort of 816 dementia-free subjects from an Italian population-based study constituted this sample. Dementia was defined on the basis of the clinical criteria of the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition and AD was diagnosed on the basis of the National Institute of Neurological and Communicative Disease and Stroke-Alzheimer's Disease and Related Disorders Association criteria. Baseline measures were taken for plasma tHcy, serum B vitamins and apolipoprotein E gcnotype.

Over an average follow-up of four years, dementia developed in 112 subjects, including 70 who received a diagnosis of AD. Hyperhomocysteinemia was present in 26.6% of the subjects. Those with hyperhomocysteinemia were more likely to develop dementia and AD with a hazard ratio for dementia of 2.08 and for AD of 2.11. Low folate concentrations were also associated with an increased risk of both dementia and AD, whereas the association was not significant for vitamin B- 12.

The results show that hyperhomocysteinemia doubles the risk of developing dementia and AD independently of several major confounders. A limiting factor of this study was the lack of standardized cutoffs for hyperhomocysteinemia forced the authors to calculate their own reference intervals. In addition, the single time measurement of tHcy and the evaluation of B vitamin status were both limitations as well. Although B vitamin supplementation is recognized as the most effective means for lowering Hey concentrations, there have been no prospective trials of the effect of vitamin supplementation on the incidence of dementia. Therefore, the findings can not be used as basis for treatment recommendations and further studies in this area are necessary.

Giovanni Ravaglia, Paola Forti, Fabiola Maioli, et al. Homocysteine and Folate as Risk Factors for Dementia and Alzheimer Disease. AJCN; 82: (September 2005) [Address reprint requests to G. Ravaglia, Department of Internal Medicine, Cardioangiology, and Hepatology, University Hospital S Orsola-Malpighi, Via Massarenti, 9-40138 Bologna, Italy. E-mail: ravaglia@med.unibo.it].