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一种生物利用型姜黄素对非痴呆成人的记忆和大脑淀粉样蛋白和tau 的影响:一项为期 18 个月的双盲、安慰剂对照试验。

Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial.

机构信息

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, UCLA Longevity Center, Department of Molecular and Medical Pharmacology, and Center for Human Nutrition, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA.

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, UCLA Longevity Center, Department of Molecular and Medical Pharmacology, and Center for Human Nutrition, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA.

出版信息

Am J Geriatr Psychiatry. 2018 Mar;26(3):266-277. doi: 10.1016/j.jagp.2017.10.010. Epub 2017 Oct 27.

DOI:10.1016/j.jagp.2017.10.010
PMID:29246725
Abstract

OBJECTIVE

Because curcumin's anti-inflammatory properties may protect the brain from neurodegeneration, we studied its effect on memory in non-demented adults and explored its impact on brain amyloid and tau accumulation using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile positron emission tomography (FDDNP-PET).

METHODS

Forty subjects (age 51-84 years) were randomized to a bioavailable form of curcumin (Theracurmin® containing 90 mg of curcumin twice daily [N = 21]) or placebo (N = 19) for 18 months. Primary outcomes were verbal (Buschke Selective Reminding Test [SRT]) and visual (Brief Visual Memory Test-Revised [BVMT-R]) memory, and attention (Trail Making A) was a secondary outcome. FDDNP-PET signals (15 curcumin, 15 placebo) were determined in amygdala, hypothalamus, medial and lateral temporal, posterior cingulate, parietal, frontal, and motor (reference) regions. Mixed effects general linear models controlling for age and education, and effect sizes (ES; Cohen's d) were estimated.

RESULTS

SRT Consistent Long-Term Retrieval improved with curcumin (ES = 0.63, p = 0.002) but not with placebo (ES = 0.06, p = 0.8; between-group: ES = 0.68, p = 0.05). Curcumin also improved SRT Total (ES = 0.53, p = 0.002), visual memory (BVMT-R Recall: ES = 0.50, p = 0.01; BVMT-R Delay: ES = 0.51, p = 0.006), and attention (ES = 0.96, p < 0.0001) compared with placebo (ES = 0.28, p = 0.1; between-group: ES = 0.67, p = 0.04). FDDNP binding decreased significantly in the amygdala with curcumin (ES = -0.41, p = 0.04) compared with placebo (ES = 0.08, p = 0.6; between-group: ES = 0.48, p = 0.07). In the hypothalamus, FDDNP binding did not change with curcumin (ES = -0.30, p = 0.2), but increased with placebo (ES = 0.26, p = 0.05; between-group: ES = 0.55, p = 0.02).

CONCLUSIONS

Daily oral Theracurmin may lead to improved memory and attention in non-demented adults. The FDDNP-PET findings suggest that symptom benefits are associated with decreases in amyloid and tau accumulation in brain regions modulating mood and memory.

摘要

目的

由于姜黄素的抗炎特性可能保护大脑免受神经退行性变的影响,我们研究了其在非痴呆成年人中的记忆作用,并通过 2-(1-{6-[(2-[F-18]氟乙基)(甲基)氨基]-2-萘基}亚乙基)丙二腈正电子发射断层扫描 (FDDNP-PET) 来探索其对大脑淀粉样蛋白和 tau 积累的影响。

方法

40 名受试者(年龄 51-84 岁)被随机分配至生物可利用的姜黄素(Theracurmin®,每天两次含有 90mg 姜黄素 [N=21])或安慰剂(N=19)治疗 18 个月。主要结局是语言(Buschke 选择性提醒测试[SRT])和视觉(简短视觉记忆测试修订版[BVMT-R])记忆,注意力(Trail Making A)是次要结局。在杏仁核、下丘脑、内侧和外侧颞叶、后扣带回、顶叶、额叶和运动(参考)区域确定 15 例姜黄素和 15 例安慰剂的 FDDNP-PET 信号。采用混合效应一般线性模型控制年龄和教育,并估计效应大小(ES;Cohen's d)。

结果

姜黄素治疗后 SRT 持续长期检索改善(ES=0.63,p=0.002),而安慰剂治疗后无改善(ES=0.06,p=0.8;组间:ES=0.68,p=0.05)。姜黄素还改善了 SRT 总得分(ES=0.53,p=0.002)、视觉记忆(BVMT-R 回忆:ES=0.50,p=0.01;BVMT-R 延迟:ES=0.51,p=0.006)和注意力(ES=0.96,p<0.0001),与安慰剂相比(ES=0.28,p=0.1;组间:ES=0.67,p=0.04)。与安慰剂相比,姜黄素治疗后杏仁核中的 FDDNP 结合显著减少(ES=-0.41,p=0.04)(ES=0.08,p=0.6;组间:ES=0.48,p=0.07)。在下丘脑,姜黄素治疗后 FDDNP 结合无变化(ES=-0.30,p=0.2),而安慰剂治疗后增加(ES=0.26,p=0.05;组间:ES=0.55,p=0.02)。

结论

每日口服 Theracurmin 可能会改善非痴呆成年人的记忆和注意力。FDDNP-PET 结果表明,症状改善与大脑中调节情绪和记忆的区域中淀粉样蛋白和 tau 积累的减少有关。

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