A multimodal lifestyle intervention complemented with epigallocatechin gallate to prevent cognitive decline in APOE- ɛ4 carriers with Subjective Cognitive Decline: a randomized, double-blinded clinical trial (PENSA study).

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The Journal of Prevention of Alzheimer's Disease Pub Date : 2025-07-14 DOI:10.1016/j.tjpad.2025.100271

Laura Forcano, Natalia Soldevila-Domenech, Anna Boronat, Gonzalo Sánchez-Benavides, Albert Puig-Pijoan, Thais Lorenzo, Ana Aldea-Perona, Marc Suárez-Calvet, Aida Cuenca-Royo, Juan Domingo Gispert, Maria Gomis-Gonzalez, Carolina Minguillón, Patrícia Diaz-Pellicer, Karine Fauria, Iris Piera, Klaus Langohr, Mara Dierssen, Nieves Pizarro, Esther Mur-Gimeno, Oriol Grau-Rivera, José Luis Molinuevo, Rafael de la Torre

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Abstract

Background: 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.

Objectives: To assess whether the addition of a green tea extract enriched with epigallocatechin-3-gallate (EGCG) enhances the effects of an MLI.

Design: Double-blind, randomized, two-arm, and placebo-controlled trial. Exploratory comparisons were made with a non-randomized group (NRG) receiving healthy lifestyle recommendations.

Setting: 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.

Measurements: Primary endpoint was change in the modified Preclinical Alzheimer Cognitive Composite (PACC-exe) score.

Results: 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.

Conclusions: 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.

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一项多模式生活方式干预与表没食子儿茶素没食子酸酯一起预防APOE- 4携带者认知能力下降的主观认知能力下降：一项随机、双盲临床试验（PENSA研究）。

背景：在认知障碍高危人群中，膳食化合物增强多模式生活方式干预（MLIs）对认知影响的潜力尚不清楚。目的：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的作用。设计：双盲、随机、双组、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。背景：在西班牙巴塞罗那进行的基于人群的研究参与者：年龄在60-80岁的APOE- 4携带者，主观认知能力下降干预：12个月的强化MLI，包括饮食咨询、指导体育活动和认知刺激，结合EGCG （5-6 mg/kg）或安慰剂，随后是3个月的洗脱期。测量：主要终点是改良的临床前阿尔茨海默认知复合（PACC-exe）评分的变化。结果：129名参与者（65.1%，84名女性，年龄66.7±5.5岁）入组（52名MLI+EGCG， 52名MLI+安慰剂，25名NRG），其中126名（97.7%）纳入改良意向治疗分析。12个月后，MLI+EGCG与MLI+安慰剂在PACC-exe中的差异无统计学意义(调整后平均差异[AMD]: 0.12；95%ci: -0.01, 0.24；p = 0.061)。然而，MLI+EGCG组的参与者表现出可靠的认知改善的可能性是前者的2.6倍。在3个月的洗脱期后的探索性分析中，与MLI+安慰剂相比，MLI+EGCG组显示出显著的认知益处(AMD: 0.19；95%ci: 0.06, 0.32；p = 0.005)。与NRG的探索性比较也表明，两个MLI组在认知能力和痴呆风险降低方面都有更大的提高，尤其是EGCG组。结论：虽然没有达到主要结果，但这项概念验证试验表明，将MLIs与EGCG联合使用值得在更大规模的验证性研究中进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

The Journal of Prevention of Alzheimer's Disease Medicine-Psychiatry and Mental Health

CiteScore

9.20

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0.00%

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期刊介绍： The JPAD Journal of Prevention of Alzheimer’Disease will publish reviews, original research articles and short reports to improve our knowledge in the field of Alzheimer prevention including: neurosciences, biomarkers, imaging, epidemiology, public health, physical cognitive exercise, nutrition, risk and protective factors, drug development, trials design, and heath economic outcomes.JPAD will publish also the meeting abstracts from Clinical Trial on Alzheimer Disease (CTAD) and will be distributed both in paper and online version worldwide.We hope that JPAD with your contribution will play a role in the development of Alzheimer prevention.