Forcano Laura, Soldevila-Domenech Natalia, Boronat Anna, Sánchez-Benavides Gonzalo, Puig-Pijoan Albert, Lorenzo Thais, Aldea-Perona Ana, Suárez-Calvet Marc, Cuenca-Royo Aida, Gispert Juan Domingo, Gomis-Gonzalez Maria, Minguillón Carolina, Diaz-Pellicer Patrícia, Fauria Karine, Piera Iris, Langohr Klaus, Dierssen Mara, Pizarro Nieves, Mur-Gimeno Esther, Grau-Rivera Oriol, Molinuevo José Luis, de la Torre Rafael
Integrative Pharmacology and Systems Neuroscience Research Group, Neuroscience Research Program, Hospital del Mar Research Institute, Barcelona, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
Integrative Pharmacology and Systems Neuroscience Research Group, Neuroscience Research Program, Hospital del Mar Research Institute, Barcelona, Spain; Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
J Prev Alzheimers Dis. 2025 Sep;12(8):100271. doi: 10.1016/j.tjpad.2025.100271. Epub 2025 Jul 15.
The potential of dietary compounds to enhance the effects of multimodal lifestyle interventions (MLIs) on cognition in individuals at high risk of cognitive impairment remains unclear.
To assess whether the addition of a green tea extract enriched with epigallocatechin-3-gallate (EGCG) enhances the effects of an MLI.
Double-blind, randomized, two-arm, and placebo-controlled trial. Exploratory comparisons were made with a non-randomized group (NRG) receiving healthy lifestyle recommendations.
Population-based study conducted in Barcelona, Spain PARTICIPANTS: APOE-ɛ4 carriers aged 60-80 with subjective cognitive decline INTERVENTION: A 12-month intensive MLI including dietary counseling, guided physical activity, and cognitive stimulation, combined with EGCG (5-6 mg/kg) or placebo, followed by a 3-month washout.
Primary endpoint was change in the modified Preclinical Alzheimer Cognitive Composite (PACC-exe) score.
129 participants (65.1% 84 women, aged 66.7±5.5 years) were enrolled (52 MLI+EGCG, 52 MLI+placebo and 25 NRG), with126 (97.7%) included in the modified intention-to-treat analysis. After 12 months, no statistically significant difference was observed between MLI+EGCG and MLI+placebo in the PACC-exe (adjusted mean difference [AMD]: 0.12; 95%CI: -0.01, 0.24; p=0.061). However, participants in the MLI+EGCG group were 2.6 times more likely to show a reliable cognitive improvement. In exploratory analyses following a 3-month washout, the MLI+EGCG group showed significant cognitive benefits compared to the MLI+placebo (AMD: 0.19; 95%CI: 0.06, 0.32; p=0.005). Exploratory comparisons with the NRG also suggested greater gains in cognition and dementia risk reduction in both MLI groups, particularly with EGCG.
While the primary outcome was not met, this proof-of-concept trial suggests that combining MLIs with EGCG warrants further investigation in larger, confirmatory studies.
饮食化合物增强多模式生活方式干预（MLI）对认知功能受损高风险个体认知影响的潜力尚不清楚。
评估添加富含表没食子儿茶素-3-没食子酸酯（EGCG）的绿茶提取物是否能增强MLI的效果。
双盲、随机、双臂、安慰剂对照试验。与接受健康生活方式建议的非随机组（NRG）进行探索性比较。
在西班牙巴塞罗那进行的基于人群的研究
60 - 80岁有主观认知下降的载脂蛋白E-ε4携带者
为期12个月的强化MLI，包括饮食咨询、有指导的体育活动和认知刺激，同时服用EGCG（5 - 6毫克/千克）或安慰剂，随后有3个月的洗脱期。
主要终点是改良的临床前阿尔茨海默病认知综合评分（PACC-exe）的变化。
共纳入129名参与者（65.1%为84名女性，年龄66.7±5.5岁）（52名MLI + EGCG组，52名MLI + 安慰剂组和25名NRG组），126名（97.7%）纳入改良意向性分析。12个月后，MLI + EGCG组和MLI + 安慰剂组在PACC-exe上未观察到统计学显著差异（调整后平均差异[AMD]：0.12；95%置信区间：-0.01，0.24；p = 0.061）。然而，MLI + EGCG组的参与者出现可靠认知改善的可能性高出2.6倍。在3个月洗脱期后的探索性分析中，与MLI + 安慰剂组相比，MLI + EGCG组显示出显著的认知益处（AMD：0.19；95%置信区间：0.06，0.32；p = 0.005）。与NRG组的探索性比较也表明，两个MLI组在认知改善和痴呆风险降低方面有更大的获益，尤其是使用EGCG的组。
虽然未达到主要结局，但这项概念验证试验表明，将MLI与EGCG联合应用值得在更大规模的验证性研究中进一步探究。
