journal articles
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)
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, the PENSA working group
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.
CITATION:
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 ; the PENSA working group (2025): 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). The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100271