Max Planck Institute for Human Cognitive and Brain Sciences, Department of Neurology, Stephanstr. 1A, 04103 Leipzig, Germany; Collaborative Research Centre 1052 'Obesity Mechanisms', Subproject A1, Faculty of Medicine, University of Leipzig, Leipzig, Germany.
Max Planck Institute for Human Cognitive and Brain Sciences, Department of Neurology, Stephanstr. 1A, 04103 Leipzig, Germany.
Neuroimage. 2018 Jul 1;174:177-190. doi: 10.1016/j.neuroimage.2018.03.023. Epub 2018 Mar 13.
The polyphenol resveratrol has been suggested to exert beneficial effects on memory and the aging hippocampus due to calorie-restriction mimicking effects. However, the evidence based on human interventional studies is scarce. We therefore aimed to determine the effects of resveratrol on memory performance, and to identify potential underlying mechanisms using a broad array of blood-based biomarkers as well as hippocampus connectivity and microstructure assessed with ultra-high field magnetic resonance imaging (UHF-MRI).
In this double-blind, randomized controlled trial, 60 elderly participants (60-79 years) with a wide body-mass index (BMI) range of 21-37 kg/m were randomized to receive either resveratrol (200 mg/day) or placebo for 26 weeks (registered at ClinicalTrials.gov: NCT02621554). Baseline and follow-up assessments included the California Verbal Learning Task (CVLT, main outcome), the ModBent task, anthropometry, markers of glucose and lipid metabolism, inflammation and neurotrophins derived from fasting blood, multimodal neuroimaging at 3 and 7 T, and questionnaires to assess confounding factors.
Multivariate repeated-measures ANOVA did not detect significant time by group effects for CVLT performance. There was a trend for preserved pattern recognition memory after resveratrol, while performance decreased in the placebo group (n.s., p = 0.07). Further exploratory analyses showed increases in both groups over time in body fat, cholesterol, fasting glucose, interleukin 6, high sensitive C-reactive protein, tumor necrosis factor alpha and in mean diffusivity of the subiculum and presubiculum, as well as decreases in physical activity, brain-derived neurotrophic factor and insulin-like growth factor 1 at follow-up, which were partly more pronounced after resveratrol.
This interventional study failed to show significant improvements in verbal memory after 6 months of resveratrol in healthy elderly with a wide BMI range. A non-significant trend emerged for positive effects on pattern recognition memory, while possible confounding effects of unfavorable changes in lifestyle behavior, neurotrophins and inflammatory markers occurred. Our findings also indicate the feasibility to detect (un)healthy aging-related changes in measures of hippocampus microstructure after 6 months using 7T diffusion MRI. More studies incorporating a longer duration and larger sample size are needed to determine if resveratrol enhances memory performance in healthy older adults.
由于具有模拟热量限制的效果，多酚白藜芦醇已被证明对记忆和衰老的海马体有益。但是，基于人体干预研究的证据很少。因此，我们旨在使用广泛的基于血液的生物标志物以及超高场磁共振成像（UHF-MRI）来确定白藜芦醇对记忆表现的影响，并确定潜在的潜在机制。
在这项双盲，随机对照试验中，将 60 名年龄在 60-79 岁之间，体重指数（BMI）范围广泛为 21-37 kg/m 的老年人随机分为两组，分别接受白藜芦醇（200mg/天）或安慰剂治疗 26 周（在 ClinicalTrials.gov 上注册：NCT02621554）。基线和随访评估包括加利福尼亚语言学习任务（CVLT，主要结局），ModBent 任务，人体测量，血糖和脂质代谢，炎症和神经发生标志物的测量，来自空腹血液的多模态神经影像学检查，以及评估混杂因素的问卷。
多变量重复测量方差分析未检测到 CVLT 表现的时间与组之间的显着影响。白藜芦醇组的模式识别记忆有保留趋势，而安慰剂组的表现下降（无统计学意义，p=0.07）。进一步的探索性分析显示，两组在随访过程中，体脂肪，胆固醇，空腹血糖，白细胞介素 6，高敏 C 反应蛋白，肿瘤坏死因子-α和 subiculum 和 presubiculum 的平均扩散率均增加，而体力活动，脑源性神经营养因子和胰岛素样生长因子 1 则减少，这在白藜芦醇后更为明显。
这项干预性研究未能显示出在 BMI 范围广泛的健康老年人中，经过 6 个月的白藜芦醇治疗后，在言语记忆方面有明显改善。在模式识别记忆方面出现了积极影响的非显着趋势，而生活方式行为，神经发生因子和炎症标志物的不利变化可能产生了混杂影响。我们的研究结果还表明，使用 7T 扩散 MRI，在 6 个月后，可以检测到（不健康）与衰老相关的海马体微观结构变化的可行性。需要进行更多的研究，包括更长的时间和更大的样本量，以确定白藜芦醇是否可以增强健康老年人的记忆表现。
