Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Neurology, Lin-Shin Hospital, Taichung, Taiwan.
Biol Psychiatry. 2014 May 1;75(9):678-85. doi: 10.1016/j.biopsych.2013.08.010. Epub 2013 Sep 25.
N-methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission is vital for learning and memory. Hypofunction of NMDAR has been reported to play a role in the pathophysiology of Alzheimer disease (AD), particularly in the early phase. Enhancing NMDAR activation might be a novel treatment approach. One of the methods to enhance NMDAR activity is to raise the levels of NMDA coagonists by blocking their metabolism. This study examined the efficacy and safety of sodium benzoate, a D-amino acid oxidase inhibitor, for the treatment of amnestic mild cognitive impairment and mild AD.
We conducted a randomized, double-blind, placebo-controlled trial in four major medical centers in Taiwan. Sixty patients with amnestic mild cognitive impairment or mild AD were treated with 250-750 mg/day of sodium benzoate or placebo for 24 weeks. Alzheimer's Disease Assessment Scale-cognitive subscale (the primary outcome) and global function (assessed by Clinician Interview Based Impression of Change plus Caregiver Input) were measured every 8 weeks. Additional cognition composite was measured at baseline and endpoint.
Sodium benzoate produced a better improvement than placebo in Alzheimer's Disease Assessment Scale-cognitive subscale (p = .0021, .0116, and .0031 at week 16, week 24, and endpoint, respectively), additional cognition composite (p = .007 at endpoint) and Clinician Interview Based Impression of Change plus Caregiver Input (p = .015, .016, and .012 at week 16, week 24, and endpoint, respectively). Sodium benzoate was well-tolerated without evident side-effects.
Sodium benzoate substantially improved cognitive and overall functions in patients with early-phase AD. The preliminary results show promise for D-amino acid oxidase inhibition as a novel approach for early dementing processes.
N-甲基-D-天冬氨酸受体（NMDAR）介导的神经传递对学习和记忆至关重要。据报道，NMDAR 功能低下在阿尔茨海默病（AD）的病理生理学中起作用，尤其是在早期阶段。增强 NMDAR 的激活可能是一种新的治疗方法。增强 NMDAR 活性的一种方法是通过阻断其代谢来提高 NMDA 共激动剂的水平。本研究考察了苯甲酸钠（一种 D-氨基酸氧化酶抑制剂）治疗遗忘型轻度认知障碍和轻度 AD 的疗效和安全性。
我们在台湾的四家主要医学中心进行了一项随机、双盲、安慰剂对照试验。60 例遗忘型轻度认知障碍或轻度 AD 患者接受苯甲酸钠（250-750 mg/天）或安慰剂治疗 24 周。每 8 周测量一次阿尔茨海默病评估量表认知子量表（主要结局）和整体功能（由临床医生访谈基于变化的印象加上照顾者投入评估）。在基线和终点测量额外的认知综合指标。
苯甲酸钠在阿尔茨海默病评估量表认知子量表（p =.0021，.0116，.0031，分别在第 16 周、第 24 周和终点）、额外认知综合指标（p =.007，在终点）和临床医生访谈基于变化的印象加上照顾者投入（p =.015，.016，.012，分别在第 16 周、第 24 周和终点）方面的改善优于安慰剂。苯甲酸钠耐受良好，无明显副作用。
苯甲酸钠可显著改善早期 AD 患者的认知和整体功能。初步结果表明，D-氨基酸氧化酶抑制可能是治疗早期痴呆进程的一种新方法。
