HIGH DOSE SUPPLEMENTS TO TREAT ALZHEIMER'S DISEASE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项由美国国立卫生研究院资助的多中心试验，旨在验证降低同型半胱氨酸水平（在阿尔茨海默病（AD）患者中经常升高）将减缓认知能力下降速度的主要假设。次要终点包括：1)确定这种减少是否也对行为、日常生活活动、全球地位和生活质量的测量产生有利影响；2)检测ApoE和亚甲基四氢叶酸还原酶基因型是否影响AD患者同型半胱氨酸的减少；3)确定大剂量补充剂长期治疗AD患者的安全性和耐受性。阿尔茨海默病是一种毁灭性的疾病，也是一个重大的公共卫生问题。显然，减缓疾病进展和/或改善生活质量的治疗是非常重要的。目前，没有直接证据表明同型半胱氨酸水平升高与AD的进展有因果关系，只有数据表明同型半胱氨酸水平升高是AD的一个危险因素。本研究旨在测试叶酸、维生素B6和B12的组合是否会影响AD的进展和/或生活质量。这是一项III期平行设计研究，两组受试者规模不等，其中60%接受补充剂，40%接受安慰剂。治疗时间为18个月。总共将有400名患者入组，其中15名患者在该地点入组，其中10名患者将使用GCRC。在18个月的研究期间，患者将接受体格检查和相当标准的实验室检查，以及每次8次门诊检查的功能和行为测试。准备基因组DNA进行多态性分析。受试者继续参加本研究。目前还没有初步的调查结果。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is an NIH-funded multicenter trial to test the primary hypothesis that reduction of homocysteine levels, which are frequently elevated in patients with Alzheimer's disease (AD), will slow the rate of cognitive decline. Secondary endpoints include 1) determining whether such reductions also favorably influence measures of behavior, activities of daily living, global status, quality of life; 2) examining whether ApoE and methylenetetrahydrofolate reductase genotypes influence homocysteine reduction in subjects with AD; and 3) determining the safety and tolerability of long-term treatment of AD subjects with high-dose supplements. Alzheimer's disease is a devastating disease and a major public health problem. Clearly, treatments that may slow disease progression and/or improve quality of life are of great significance. At present, there is no direct evidence causally linking elevations in homocysteine levels with AD progression, only data suggesting that elevated homocysteine levels are a risk factor for AD. This study is designed to test whether a combination of folate, Vitamin B6 and B12 will influence the progression of AD and/or quality of life. It is a Phase III, parallel-design study with two groups of unequal size - 60% receiving supplements and 40% placebo. Treatment duration will be for 18 months. A total of 400 patients will be enrolled overall, with 15 enrolled at this site, of which 10 will use the GCRC. Patients will undergo physical exam and a fairly standard laboratory examination, as well as functional and behavioral testing at each of 8 outpatient visits over the 18-month study period. Genomic DNA will be prepared for polymorphism analysis. Subjects continue to be enrolled on this study. No preliminary findings have been reported yet.