Morris Martha Savaria
Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
Lancet Neurol. 2003 Jul;2(7):425-8. doi: 10.1016/s1474-4422(03)00438-1.
A high circulating concentration of the amino acid homocysteine is an independent risk factor for stroke. Alzheimer's disease (AD) commonly co-occurs with stroke. Epidemiological studies found associations between hyperhomocysteinaemia and both histologically confirmed AD and disease progression and revealed that dementia in AD was associated with evidence of brain infarcts on autopsy. Thus, hyperhomocysteinaemia and AD could be linked by stroke or microvascular disease. However, given known relations between B-group-vitamin deficiency and both hyperhomocysteinaemia and neurological dysfunction, direct causal mechanisms are also plausible.
A recent prospective study (S Seshadri and colleagues N Engl J Med; 2002 346: 476-83) showed hyperhomocysteinaemia to be a strong, independent risk factor for dementia and AD. The researchers found a graded increase in risk of both outcomes with rising plasma concentration of homocysteine after multivariate control for putative risk factors for AD. In conjunction with demonstration of a fall in homocysteine concentrations in response to increasing B-group-vitamin status, these findings give hope that mental decline, or AD itself, could be prevented by dietary modification or food fortification. WHERE NEXT? 25% of dementia cases are attributed to stroke. The possibility that some of the other 75% might be prevented by the lowering of homocysteine concentrations greatly increases the hope of maintaining self-sufficiency into old age. If homocysteine lowering can reduce the incidence of dementia or AD, decreased incidence of these disorders may be seen in Canada and the USA, where government-mandated folate-fortification programmes are in effect. Future research should focus on early detection of AD and on the possibility that the disease itself, or its primary symptom, could be prevented by folate supplementation.
血液中氨基酸同型半胱氨酸浓度升高是中风的独立危险因素。阿尔茨海默病（AD）常与中风同时发生。流行病学研究发现高同型半胱氨酸血症与组织学确诊的AD及疾病进展之间存在关联，并揭示AD中的痴呆与尸检时脑梗死证据相关。因此，高同型半胱氨酸血症与AD可能通过中风或微血管疾病相联系。然而，鉴于已知B族维生素缺乏与高同型半胱氨酸血症及神经功能障碍之间的关系，直接的因果机制也有可能。
最近一项前瞻性研究（S·塞沙德里及其同事，《新英格兰医学杂志》；2002年，346卷：476 - 483页）表明，高同型半胱氨酸血症是痴呆和AD的一个强有力的独立危险因素。研究人员在对AD的假定危险因素进行多变量控制后发现，随着血浆同型半胱氨酸浓度升高，这两种结果的风险呈分级增加。结合表明随着B族维生素水平升高同型半胱氨酸浓度下降的证据，这些发现让人希望通过饮食调整或食物强化来预防智力衰退或AD本身。
25%的痴呆病例归因于中风。通过降低同型半胱氨酸浓度预防另外75%病例中的部分病例的可能性大大增加了维持老年生活自理能力的希望。如果降低同型半胱氨酸能降低痴呆或AD的发病率，那么在加拿大和美国可能会看到这些疾病发病率下降，因为这两个国家实施了政府强制的叶酸强化计划。未来的研究应聚焦于AD的早期检测以及通过补充叶酸预防该疾病本身或其主要症状的可能性。
