Home › Research › Treatments
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)
Forcano L, Soldevila-Domenech N, Boronat A, Sánchez-Benavides G, Puig-Pijoan A, Lorenzo T, Aldea-Perona A, Suárez-Calvet M et al.. The journal of prevention of Alzheimer's disease, 2025-07-15
Topic: Brain proteins, microglia and lab models
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.
Key findings
- 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).
- 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).
- 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.
Why it matters
Adding green tea extract with EGCG to a lifestyle program did not significantly improve the main cognitive score after 12 months compared with lifestyle alone. Some benefit appeared after a washout, but this was exploratory and not the main finding.
New to this subject? Start with our plain-English guide: Treatments →
Study details
- Participants129
- Effect size65.1%; 97.7%
- Evidence strengthHigh
How this study scored 64/100
Published in a peer-reviewed journal, and it is a randomised controlled trial.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The journal of prevention of Alzheimer's disease) |
| Journal's citation record | 0 / 4 | The Journal of Prevention of Alzheimer s Disease: journal h-index 63 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 129 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 2 / 7 | Cited 7 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 4.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Rafael de la Torre: h-index 90 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Universitat Autònoma de Barcelona: institution h-index 782 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 16 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40664536) |
| Free to read | 2 / 2 | Free to read |
| Total | 64 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.tjpad.2025.100271
- PubMed: 40664536
- Original source →
- Free full text: The Journal of Prevention of Alzheimer s Disease →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Forcano, L., Soldevila-Domenech, N., Boronat, A., Sánchez-Benavides, G., Puig-Pijoan, A., Lorenzo, T., et al. (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. https://doi.org/10.1016/j.tjpad.2025.100271
Vancouver
Forcano L, Soldevila-Domenech N, Boronat A, Sánchez-Benavides G, Puig-Pijoan A, Lorenzo T, et al. 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. 2025. doi:10.1016/j.tjpad.2025.100271. PMID: 40664536.
BibTeX
@article{forcano2025-40664536,
author = {Forcano, L. and Soldevila-Domenech, N. and Boronat, A. and Sánchez-Benavides, G. and Puig-Pijoan, A. and Lorenzo, T. and Aldea-Perona, A. and Suárez-Calvet, M. and others},
title = {{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)}},
journal = {The journal of prevention of Alzheimer's disease},
year = {2025},
doi = {10.1016/j.tjpad.2025.100271},
pmid = {40664536},
url = {https://doi.org/10.1016/j.tjpad.2025.100271}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.