Prevention of cognitive decline in subjective cognitive decline APOE‐ε4 carriers after Epigallocatechin gallate and a multimodal intervention, the PENSA study: 1‐year follow‐up results of the randomized controlled trial
Authors: Forcano Laura , Boronat Anna , Lorenzo Thais , Cuenca Aida , Soldevila‐Domenech Natalia , Pizarro Nieves , Puig‐Pijoan Albert , Piera Iris , Gomis Maria , Diaz‐Pellicer Patricia , Torre Rafael , Grau‐Rivera Oriol , Sánchez‐Benavides Gonzalo , Fauria Karine , Minguillón Carolina , Molinuevo Jose Luis , Gispert Juan Domingo 
Published: December 2023

Background

Preventive approaches such as lifestyle interventions targeting multiple Alzheimer’s disease (AD) risk or preventive factors are effective strategies to prevent cognitive decline. Additionally, there are reports on synergistic effects between different lifestyle intervention components and food supplements or pharmacological approaches, aiming to improve the intervention’s efficacy. In terms of delivery, trials have started to incorporate new technologies to optimize the implementation and management of interventions.

Method

The PENSA study, framed within the World‐Wide Fingers network, is a randomized, double‐blind clinical trial aiming to evaluate the efficacy of a personalized multimodal lifestyle intervention (diet, physical activity, cognitive/social stimulation) combined with epigallocatechin gallate (EGCG) over 12 months, in slowing down cognitive decline and improving brain connectivity. Continuous measures of dietary behavior, physical activity, cognitive training performance and mental health are collected through eHealth and mHealth tools/devices. 129 individuals aged 60‐80 years (65.1% females; 67.2±4.6 years), meeting subjective cognitive decline (SCD) criteria, carrying the APOE‐ε4 allele were enrolled and randomized into three treatment arms (multimodal intervention [MC] +EGCG/placebo, or lifestyle recommendations [CG]). The primary efficacy outcome is cognitive performance measured with the ADCS‐PACC‐plus‐exe. Results of participants’ data collected until January 2023 are included in the present study (MC: N = 104 at baseline, N = 97 at 6 months; CG: N = 25 at baseline, N = 22 at 6 months).

Result

After 6 months, significant cognitive improvements are shown in the MC vs CG as measured by the ADCS‐PACC‐plus‐exe (Cohen’s d = 0.38) as well as the MoCA (Cohen’s d = 0.53). MC vs CG participants, showed greater adherence to the MedDiet (mean 76,8±10,9% vs. 60,9±14,9%). Regarding the MC intervention, adherence to physical and cognitive stimulation activities, was 85,0% and 75,0%, respectively. Average rate of response along the intervention to daily/weekly Ecological Momentary Assessments (mHealth prompts assessing diet, mood, physical activity and social stimulation) was 79,5%. Updated 1‐year follow‐up data will be presented in the meeting.

Conclusion

A personalized multimodal lifestyle intervention addressed to cognitively healthy people at higher risk of developing AD is a feasible and appears an effective treatment to prevent cognitive decline. The intensity of the intervention and the use of new technologies are appropriate for this population.