Background Current anti-dementia drugs cannot benefit mild cognitive impairment (MCI). Sodium benzoate (a D-amino acid oxidase [DAO] inhibitor) has been found to improve the cognitive function of patients with early-phase Alzheimer’s disease (mild Alzheimer’s disease or MCI). However, its effect on brain function remains unknown. This study aimed to evaluate the influence of benzoate on functional magnetic resonance imaging in patients with amnestic MCI. Methods This was a 24-week, randomized, double-blind, placebo-controlled trial that enrolled 21 patients with amnestic MCI and allocated them randomly to either of 2 treatment groups: (1) benzoate group (250–1500 mg/d), or (2) placebo group. We assessed the patients’ working memory, verbal learning and memory, and resting-state functional magnetic resonance imaging and regional homogeneity (ReHo) maps at baseline and endpoint. Results Resting-state ReHo decreased in right orbitofrontal cortex after benzoate treatment but did not change after placebo. Moreover, after benzoate treatment, the change in working memory was positively correlated with the change in ReHo in right precentral gyrus and right middle occipital gyrus; and the change in verbal learning and memory was positively correlated with the change in ReHo in left precuneus. In contrast, after placebo treatment, the change in working memory or in verbal learning and memory was not correlated with the change in ReHo in any brain region. Conclusion The current study is the first to our knowledge to demonstrate that a DAO inhibitor, sodium benzoate herein, can alter brain activity as well as cognitive functions in individuals with MCI. The preliminary finding lends supports for DAO inhibition as a novel approach for early dementing processes.

中文翻译：

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在一项随机、双盲、安慰剂对照的临床试验中，苯甲酸盐（一种 D-氨基酸氧化酶抑制剂）在轻度认知障碍患者中的​​脑活动

背景目前的抗痴呆药物不能使轻度认知障碍（MCI）受益。已发现苯甲酸钠（一种 D-氨基酸氧化酶 [DAO] 抑制剂）可改善早期阿尔茨海默病（轻度阿尔茨海默病或 MCI）患者的认知功能。然而，它对大脑功能的影响仍然未知。本研究旨在评估苯甲酸盐对遗忘型 MCI 患者功能磁共振成像的影响。方法 这是一项为期 24 周、随机、双盲、安慰剂对照的试验，招募了 21 名遗忘性 MCI 患者，并将他们随机分配到 2 个治疗组中的任何一个：（1）苯甲酸盐组（250-1500 mg/d），或（2）安慰剂组。我们评估了患者的工作记忆、语言学习和记忆，和静止状态功能磁共振成像和基线和终点的区域同质性 (ReHo) 图。结果 苯甲酸盐治疗后右眶额皮质的静息状态 ReHo 降低，但安慰剂后没有变化。此外，苯甲酸盐治疗后，工作记忆的变化与右侧中央前回和右侧枕中回的ReHo变化呈正相关；语言学习记忆的变化与左楔前叶ReHo的变化呈正相关。相比之下，在安慰剂治疗后，工作记忆或语言学习和记忆的变化与任何大脑区域的 ReHo 变化无关。结论 目前的研究是我们所知的第一个证明 DAO 抑制剂苯甲酸钠，可以改变 MCI 患者的大脑活动和认知功能。初步发现支持 DAO 抑制作为早期痴呆过程的新方法。