Renal Transplantation, Homocysteine Lowering & Cognition

描述（由申请人提供） 本申请是一项辅助研究，旨在确定同型半胱氨酸降低对认知的影响，作为肾移植受者（RTRs）正在进行的随机、对照、双盲临床试验的额外结局。 血浆同型半胱氨酸水平升高与一般人群认知功能下降相关，并显著增加血管疾病、脑血管疾病、中风和痴呆的风险。高同型半胱氨酸血症是慢性肾功能不全的普遍特征，即使在成功移植后;然而，与其他类型的慢性肾功能不全不同，高剂量的B族维生素可以降低RTR中的同型半胱氨酸水平。母试验（FAVORIT-NIH NIDDK UO1 DK61700 - 01）旨在确定降低血浆总同型半胱氨酸水平对慢性稳定性RTR中动脉粥样硬化性心血管疾病结局的影响。FAVORIT试验的目的是将4000名肾移植功能稳定> 6个月的RTR随机分配到治疗组或安慰剂组，并随访4年或直至发生心血管事件或死亡。治疗由标准的多种维生素和额外的高剂量叶酸、维生素B12和维生素B6组成，安慰剂由不含这些维生素的多种维生素组成。 本申请的具体目的是：（1）确定在该治疗方案下降低同型半胱氨酸的认知效应;和（2）表征该高风险非痴呆人群中与同型半胱氨酸和其他血管疾病风险因素相关的认知功能。为此，我们将在FAVORIT试验中随机化和3 - 4年随访后测量1000名参与者的认知结局。 该应用的结果可能在改善RTR和其他慢性肾功能不全人群的医疗保健方面具有非常重要的意义。我们的长期目标是确定认知障碍的风险因素，通过营养干预或膳食补充剂可以改变这些因素，以减少老年人和其他弱势群体中认知能力下降和痴呆症的发病率。证明降低同型半胱氨酸的认知益处可能为RTR和其他高危人群甚至普通人群的认知下降的营养改善铺平道路。

DESCRIPTION (provided by applicant) This application is for an ancillary study to determine the cognitive effects of homocysteine Iowering, as an additional outcome in an ongoing, randomized, controlled, double-blind clinical trial in renal transplant recipients (RTRs). Elevated plasma homocysteine levels are associated with diminished cognitive function in the general population, and significantly increase the risk of vascular disease, cerebrovascular disease, stroke and dementia. Hyperhomocysteinemia is a pervasive feature of chronic renal insufficiency, even after a successful transplant; however, unlike in other types of chronic renal insufficiency, homocysteine levels can be lowered in RTRs by high doses of B-vitamins. The parent trial (FAVORIT - NIH NIDDK UO1 DK61700-01) is designed to determine the effect of lowering plasma total homocysteine levels on atherosclerotic cardiovascular disease outcomes in chronic, stable RTRs. The FAVORIT trial aims to randomize 4000 RTRs with a stable functioning renal graft of > six months to a treatment or placebo group, and to follow them for 4 years or until the occurrence of a cardiovascular event or death. Treatment consists of a standard multivitamin with additional high dose folic acid, vitamin B12 and vitamin B6 and placebo consists of a multivitamin devoid of these vitamins. This application specifically aims to: (1) determine the cognitive effect of homocysteine lowering under this treatment regime; and (2), characterize cognitive function in relation to homocysteine and other risk factors for vascular disease in this high-risk, non-demented population. To do so we will measure cognitive outcomes in 1000 participants in the FAVORIT trial, at randomization and after a 3-4 year follow up. The outcome of this application may be highly significant in improving health care for RTRs and other groups with chronic renal insufficiency. Our long-term goal is to identify risk factors for cognitive impairment that can be modified through nutritional intervention or dietary supplementation in order to reduce the incidence of cognitive decline and dementia in elderly and other vulnerable populations. Demonstrating the cognitive benefits of lowering homocysteine may pave the way to nutritional modification of cognitive decline in RTRs and other high-risk groups and even in the general population.