PENSA+: Extended Follow-up of a Multimodal Lifestyle Intervention to Prevent Cognitive Decline in APOE-ε4 Carriers

Официальное название

Evaluation of the Long-Term Cognitive, Biological, and Lifestyle Effects of a Multimodal Intervention for Preventing Cognitive Decline in APOE-ε4 Carriers With Subjective Cognitive Decline

Обзор

PENSA+ is a 5-year follow-up study of participants who previously completed the PENSA clinical trial (NCT03978052), which evaluated an intensive multimodal lifestyle intervention, with or without epigallocatechin gallate (EGCG), in APOE-ε4 carriers with subjective cognitive decline, a population at increased risk of developing Alzheimer's disease. The purpose of this study is to determine whether the cognitive, biological, and lifestyle benefits observed after the original intervention are maintained over the long term. Researchers will evaluate cognitive performance, the incidence of mild cognitive impairment, dementia risk, brain imaging, blood biomarkers, physical fitness, lifestyle behaviors, and psychosocial factors approximately five years after completion of the intervention. The study will also investigate the biological and behavioral mechanisms associated with sustained cognitive benefit, identify participant characteristics associated with better long-term outcomes, evaluate the long-term cost-effectiveness of the intervention using healthcare utilization data, and explore whether lifestyle changes have influenced participants' study partners. No new intervention will be administered as part of this follow-up study.

Подробное описание

Alzheimer's disease (AD) is the leading cause of dementia and is characterized by a long preclinical phase during which pathological changes accumulate before the onset of clinical symptoms. This extended asymptomatic period provides an opportunity to implement preventive strategies aimed at delaying or reducing cognitive decline. Multidomain lifestyle interventions targeting modifiable risk factors have emerged as one of the most promising approaches for dementia prevention, demonstrating beneficial effects on cognitive performance and overall brain health, particularly in individuals at increased risk of developing AD. However, the long-term durability of these effects, the biological mechanisms underlying sustained benefit, the characteristics of individuals most likely to respond, and the long-term economic value of these interventions remain incompletely understood.

The PENSA+ study is a long-term follow-up of the PENSA randomized clinical trial (NCT03978052), which evaluated an intensive personalized multimodal lifestyle intervention in cognitively unimpaired APOE-ε4 carriers with subjective cognitive decline. The intervention combined dietary counseling, physical exercise, cognitive training, psychoeducation, social stimulation, and vascular risk management, and was administered with either epigallocatechin gallate (EGCG)-a naturally occurring green tea polyphenol with antioxidant, anti-inflammatory, metabolic, vascular, and potential neuroprotective properties-or placebo. Participants assigned to the control group received general healthy lifestyle recommendations. The original trial demonstrated improvements in cognitive performance, lifestyle behaviors, physical fitness, cardiometabolic health, and dementia risk in the intervention groups, with cognitive and lifestyle benefits persisting beyond the active intervention period. However, whether these benefits are maintained over the longer term and the mechanisms responsible for their persistence remain unknown.

The primary objective of PENSA+ is to evaluate cognitive performance, the incidence of mild cognitive impairment, and dementia risk approximately five years after completion of the original intervention. Secondary objectives are to investigate the biological, behavioral, and psychosocial mechanisms associated with sustained cognitive benefit, identify long-term responder phenotypes, and evaluate the long-term cost-effectiveness and cost-utility of the intervention. Exploratory objectives include assessing long-term clinical outcomes and healthcare resource utilization through electronic health records for up to 10 years after the intervention and evaluating potential spillover effects on participants' study partners.

Participants who completed the original PENSA trial will undergo comprehensive follow-up evaluations, including cognitive, neurological, neuroimaging, biomarker, physical fitness, lifestyle, and psychosocial assessments. Data collected during the original trial will be integrated with the five-year follow-up data to characterize long-term cognitive trajectories, identify determinants of sustained cognitive resilience, and provide evidence on the long-term clinical and economic impact of intensive multidomain lifestyle interventions for Alzheimer's disease prevention.

Первичные конечные точки

• Global Cognitive Performance (PACC-exe Composite Score) [Срок оценки: Baseline, 12 months, and approximately 5 years after completion of the original PENSA intervention]
• Incidence of Mild Cognitive Impairment (MCI) [Срок оценки: Approximately 5 years after completion of the original PENSA intervention]
• Dementia Risk (LIBRA Index) [Срок оценки: Baseline, 12 months, and approximately 5 years after completion of the original PENSA intervention]

Вторичные конечные точки (8)

• Longitudinal changes in memory and executive function [Срок оценки: Baseline, 12-month, 5-year]
• Longitudinal changes in Mediterranean diet adherence [Срок оценки: Baseline, 12-month, 5-year]
• Longitudinal changes in physical activity [Срок оценки: Baseline, 12-month, 5-year]
• Longitudinal changes in quality of life [Срок оценки: Baseline, 12-month, 5-year]
• Longitudinal changes in physical fitness - Senior Fitness Test [Срок оценки: Baseline, 12-month, 5-year]
• Longitudinal changes in physical fitness - Grip Strength Test [Срок оценки: Baseline, 12-month, 5-year]
• Longitudinal Changes in Plasma Alzheimer's Disease Biomarkers and Neuroimaging Measures [Срок оценки: Baseline, 12-month, 5-year]
• Economic Outcomes: Long-term Cost-Effectiveness and Cost-Utility [Срок оценки: Baseline, 12 months, and approximately 5 years after completion of the original PENSA intervention]

Критерии участия

Критерии включения

\- Any individual who has completed the PENSA study, does not meet any exclusion criteria, and provides consent is eligible to participate in this study.

Критерии исключения

Participants will be excluded from the study if they meet any of the following conditions:

• A prior clinical diagnosis of dementia, regardless of etiology.
• Current institutionalization (e.g., residence in nursing homes, long-term care facilities, or similar institutions).
• Impaired decision-making capacity, defined as the inability to provide informed consent independently due to cognitive, legal, or medical reasons (e.g., loss of autonomy or requirement of a legal representative).
• Current participation in another interventional clinical trial, or participation in an interventional clinical trial within the previous 3 months prior to baseline; unless deemed by the investigator not to interfere with PENSA+ procedures or outcomes.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Испания · 1 центр

• Fundació Pasqual Maragall — Barcelona

Публикации

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Идентификаторы

NCT: NCT07730671 · PENSA+_BBRC2026

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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