Seshadri Sudha
Department of Neurology, Boston University School of Medicine, 715 Albany Street B-608, Boston, MA 02118, USA.
J Alzheimers Dis. 2006 Aug;9(4):393-8. doi: 10.3233/jad-2006-9404.
Elevated plasma homocysteine (tHcy) concentrations have been associated with an increased risk of developing dementia and Alzheimer's disease (AD). It is not clear, however, if an elevation in tHcy concentration is a "risk factor" with a direct pathophysiological role in the development of the disease or merely a "risk marker" reflecting an underlying process such as oxidative stress responsible for both the high tHcy concentrations and the development of AD. Epidemiological studies have confirmed that elevations in plasma tHcy temporally precede the development of dementia and that there is a continuous, inverse linear relation between plasma tHcy concentrations and cognitive performance in older persons. Several potential biological pathways that could mediate the observed association are briefly reviewed. In light of these data and the growing parallel interest in plasma tHcy as an emerging vascular risk factor there was considerable hope that vitamin therapy with folate, B12 and B6, shown to lower plasma tHcy levels, could significantly reduce the risk of stroke and dementia permitting healthy brain aging. The results from recent trials addressing the secondary prevention of stroke and myocardial infarction trials have been disappointing. However, the role of vitamins and other homocysteine lowering treatments in the primary prevention of stroke and dementia, as well as their role in preserving cognition among persons with mild cognitive impairment and early dementia deserves to be fully pursued.
血浆同型半胱氨酸（总同型半胱氨酸，tHcy）浓度升高与患痴呆症和阿尔茨海默病（AD）风险增加相关。然而，尚不清楚tHcy浓度升高是在疾病发展中具有直接病理生理作用的“危险因素”，还是仅仅是反映潜在过程（如氧化应激，它既导致高tHcy浓度又导致AD发生）的“风险标志物”。流行病学研究已证实，血浆tHcy升高在时间上先于痴呆症的发生，且老年人血浆tHcy浓度与认知能力之间存在持续的负线性关系。本文简要综述了几种可能介导所观察到的关联的潜在生物学途径。鉴于这些数据以及人们对血浆tHcy作为一种新出现的血管危险因素的兴趣日益增加，曾有很大希望，用叶酸、维生素B12和维生素B6进行维生素治疗（已证明可降低血浆tHcy水平）能显著降低中风和痴呆症风险，实现健康的脑衰老。近期针对中风和心肌梗死二级预防试验的结果令人失望。然而，维生素及其他降低同型半胱氨酸治疗在中风和痴呆症一级预防中的作用，以及它们在轻度认知障碍和早期痴呆症患者中维持认知功能的作用，值得深入研究。
