Background: Delaying the transition from minimal cognitive impairment to Alzheimers dementia is a major concern in Alzheimers disease (AD) therapeutics. Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet effective substances are recommended. There is a need to develop new drugs to delay Alzheimers dementia. We have taken a nutritional supplement approach with genistein, a chemically defined polyphenol that acts by multimodal specific mechanisms. Our group previously showed that genistein supplementation is effective to treat the double transgenic (APP/PS1) AD animal model. Methods: In this double-blind, placebo-controlled, bicentric clinical trial we evaluated the effect of daily oral supplementation with 120 mg of genistein for 12 months on 24 early symptomatic Alzheimers patients. We used a battery of validated neurocognitive tests: Mini-Mental State Exam (MMSE), Memory Alteration Test (M@T) Clock-drawing test, Complutense Verbal Learning Test (TAVEC), Barcelona Test-Revised (TBR), and Rey Complex Figure Test. Results: We report that genistein treatment results in a significant improvement in two of the tests used (dichotomized direct TAVEC, p=0.031; dichotomized delayed centil REY copy p=0.002 and a tendency to improve in all the rest of them. The amyloid-beta deposition was analyzed using 18F-flutemetamol uptake which showed that genistein-treated patients did not increase their uptake in the anterior cingulate gyrus after treatment (p = 0.878) while placebo-treated did increase it (p=0.036) We did not observe significant changes in other brain areas studied Conclusions: This study shows that genistein may have a role in therapeutics to delay the onset of Alzheimer's dementia in patients with mild cognitive impairment. These encouraging results indicate that this should be followed up by a new study with more patients to further validate the conclusion that arises from this study. Clinical Trial Registration ID #: NCT01982578

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金雀异黄素对早期阿尔茨海默病患者认知的影响。GENIAL 临床试验

背景：延迟从最小认知障碍到阿尔茨海默病痴呆的转变是阿尔茨海默病 (AD) 治疗中的一个主要问题。AD的病理征兆出现在临床痴呆发作前数年。因此，推荐使用安全、微创且有效的物质的长期治疗方法。需要开发新的药物来延缓阿尔茨海默氏症痴呆。我们采用了染料木黄酮的营养补充方法，染料木黄酮是一种化学定义的多酚，通过多模式特定机制起作用。我们小组先前表明，金雀异黄素补充剂对治疗双转基因 (APP/PS1) AD 动物模型有效。方法：在这项双盲、安慰剂对照、双中心临床试验我们评估了每天口服补充 120 毫克染料木黄酮 12 个月对 24 名早期症状阿尔茨海默病患者的影响。我们使用了一系列经过验证的神经认知测试：简易精神状态检查 (MMSE)、记忆改变测试 (M@T) 时钟绘图测试、康普顿语言学习测试 (TAVEC)、巴塞罗那测试修订版 (TBR) 和 Rey Complex图测试。结果：我们报告说，染料木黄酮治疗导致所使用的两项测试显着改善（二分法直接 TAVEC，p=0.031；二分法延迟百分位 REY 拷贝 p=0.002，并且在所有其他测试中都有改善的趋势。淀粉样蛋白-使用 18F-flutemetamol 摄取分析 β 沉积，这表明接受金雀异黄素治疗的患者在治疗后未增加前扣带回的摄取（p = 0. 878）而安慰剂治疗确实增加了它（p = 0.036）我们没有观察到研究的其他大脑区域的显着变化结论：这项研究表明，染料木黄酮可能在治疗中发挥作用，以延迟轻度认知障碍患者的阿尔茨海默病痴呆发作减值。这些令人鼓舞的结果表明，应在此之后进行一项针对更多患者的新研究，以进一步验证本研究得出的结论。临床试验注册编号：NCT01982578 这些令人鼓舞的结果表明，应在此之后进行一项针对更多患者的新研究，以进一步验证本研究得出的结论。临床试验注册编号：NCT01982578 这些令人鼓舞的结果表明，应在此之后进行一项针对更多患者的新研究，以进一步验证本研究得出的结论。临床试验注册编号：NCT01982578