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

NCT07730671 | Not Yet Recruiting

• 1 other identifier: PENSA+_BBRC2026
• Study Type: observational
• Target: 121
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Subjective Cognitive Decline (SCD)

Keywords

Alzheimer's Disease; Dementia Prevention; Subjective Cognitive Decline; APOE-ε4 carriers; Multidomain Lifestyle Intervention; Epigallocatechin Gallate (EGCG); Brain Health; Blood Biomarkers; Long-Term Follow-up; Subjective Cognitive Decline (SCD)

Outcome Measures

Primary Outcomes (3)

• Global Cognitive Performance (PACC-exe Composite Score)

  Global cognitive performance assessed using the Preclinical Alzheimer Cognitive Composite for executive function, a composite score derived from six neuropsychological tests: Montreal Cognitive Assessment (score 0-30, higher scores indicate better cognition), Free and Cued Selective Reminding Test (score 0-48, higher scores indicate better episodic memory), Logical Memory Delayed Recall from the Wechsler Memory Scale (score 0-48, higher scores indicate better delayed verbal memory), WAIS-IV Coding (higher scores indicate better processing speed), Stroop Color-Word Test Interference score (higher scores indicate better inhibitory control and executive function), and Five Digit Test (higher scores indicate better executive functioning and cognitive flexibility). Individual test scores are converted to standardized z-scores based on the baseline mean and standard deviation of the study cohort, and the PACC-exe score is calculated as the arithmetic mean of these z-scores.

  Baseline, 12 months, and approximately 5 years after completion of the original PENSA intervention

• Incidence of Mild Cognitive Impairment (MCI)

  Incidence of Mild Cognitive Impairment determined according to clinical diagnostic criteria based on neuropsychological evaluation and clinical assessment performed at the 5-year follow-up visit. Diagnosis will require: (1) evidence of objective cognitive impairment on standardized neuropsychological assessment; (2) reported cognitive decline from previous functioning by the participant, an informant, or documented longitudinal assessment; (3) preserved independence in activities of daily living (impaired performance will be defined as below the 10th percentile, scaled score \<7, or ≥1.3 SD below age- and education-adjusted normative means); and (4) absence of dementia. Domain-specific impairment will be defined as low performance in ≥3 of 5 memory measures, ≥3 of 5 executive function measures, or ≥2 of 2 language measures. Final diagnosis will be established by a neurologist based on the integrated evaluation of neuropsychological, clinical, functional, and behavioral information.

  Approximately 5 years after completion of the original PENSA intervention

• Dementia Risk (LIBRA Index)

  Dementia risk assessed using the Lifestyle for Brain Health (LIBRA) Index, a weighted composite score of modifiable risk and protective factors for dementia. Lower scores indicate lower estimated dementia risk. The dementia risk assessed with the LIBRA Index is a weighted composite score of 12 modifiable risk and protective factors for dementia. These modifiable risks are the following: 1. Coronary heart disease 2. Chronic kidney disease 3. Hypertension 4. Hypercholesterolemia 5. Diabetes 6. Depression 7. High cognitive activity 8. Obesity 9. Low/moderate alcohol use 10. Physical inactivity 11. Smoking 12. Healthy diet

  Baseline, 12 months, and approximately 5 years after completion of the original PENSA intervention

Secondary Outcomes (8)

• Longitudinal changes in memory and executive function

  Baseline, 12-month, 5-year

• Longitudinal changes in Mediterranean diet adherence

  Baseline, 12-month, 5-year

• Longitudinal changes in physical activity

  Baseline, 12-month, 5-year

• Longitudinal changes in quality of life

  Baseline, 12-month, 5-year

• Longitudinal changes in physical fitness - Senior Fitness Test

  Baseline, 12-month, 5-year

Other Outcomes (4)

• Longer-term Clinical Outcomes and Healthcare Utilization Using EHRs (up to 10 years of follow-up)

  Baseline and within 10 years forward based on EHR

• Spillover Effect on study partners - Mediterranean diet adherence

  Approximately 5 years after termination of PENSA

• Spillover effect on study partners - physical activity levels

  Approximately 5 years after termination of PENSA

Study Arms (3)

Multimodal Lifestyle Intervention + EGCG

Participants who completed the original PENSA trial and were assigned to the intensive personalized multimodal lifestyle intervention combined with epigallocatechin gallate (EGCG) supplementation for 12 months. The intervention included dietary counseling, physical exercise, cognitive training, psychoeducation, social stimulation, and vascular risk management. Participants are followed approximately 5 years after completion of the intervention (current PENSA+ study) to evaluate long-term cognitive, biological, lifestyle, and health outcomes.

Multimodal Lifestyle Intervention + Placebo

Participants who completed the original PENSA trial and were assigned to the intensive personalized multimodal lifestyle intervention combined with placebo supplementation for 12 months. The intervention included dietary counseling, physical exercise, cognitive training, psychoeducation, social stimulation, and vascular risk management. Participants are followed approximately 5 years after completion of the intervention (current PENSA+ study) to evaluate long-term cognitive, biological, lifestyle, and health outcomes.

Control

Participants who completed the original PENSA trial and were assigned to the control group, receiving general healthy lifestyle recommendations without the intensive multimodal intervention. Participants are followed approximately 5 years after completion of the original study (current PENSA+ study) to evaluate long-term cognitive, biological, lifestyle, and health outcomes.

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals who previously completed the PENSA study will constitute the target population of this study. Of the 129 participants initially enrolled in the PENSA study, 121 completed it. Participants who completed the PENSA study were allocated as follows: * 47 participants in the MLI+EGCG group * 49 participants in the MLI+placebo group * 25 participants in the CG

You may not qualify if:

• 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.

Sponsors & Collaborators

• Barcelonabeta Brain Research Center, Pasqual Maragall Foundation: lead
• Hospital del Mar: collaborator
• Hospital del Mar Research Institute (IMIM): collaborator

Study Sites (1)

Fundació Pasqual Maragall

Barcelona, Catalonia, 08005, Spain

Location

Related Publications (15)

• Carlson MC, Parisi JM, Xia J, Xue QL, Rebok GW, Bandeen-Roche K, Fried LP. Lifestyle activities and memory: variety may be the spice of life. The women's health and aging study II. J Int Neuropsychol Soc. 2012 Mar;18(2):286-94. doi: 10.1017/S135561771100169X. Epub 2011 Dec 15.

  PMID: 22172155 BACKGROUND

• Forcano L, Soldevila-Domenech N, Boronat A, Sanchez-Benavides G, Puig-Pijoan A, Lorenzo T, Aldea-Perona A, Suarez-Calvet M, Cuenca-Royo A, Gispert JD, Gomis-Gonzalez M, Minguillon C, Diaz-Pellicer P, Fauria K, Piera I, Langohr K, Dierssen M, Pizarro N, Mur-Gimeno E, Grau-Rivera O, Molinuevo JL, de la Torre R; PENSA working group. A multimodal lifestyle intervention complemented with epigallocatechin gallate to prevent cognitive decline in APOE- varepsilon4 carriers with Subjective Cognitive Decline: a randomized, double-blinded clinical trial (PENSA study). J Prev Alzheimers Dis. 2025 Sep;12(8):100271. doi: 10.1016/j.tjpad.2025.100271. Epub 2025 Jul 15.

  PMID: 40664536 BACKGROUND

• Nishi SK, Babio N, Gomez-Martinez C, Martinez-Gonzalez MA, Ros E, Corella D, Castaner O, Martinez JA, Alonso-Gomez AM, Warnberg J, Vioque J, Romaguera D, Lopez-Miranda J, Estruch R, Tinahones FJ, Lapetra J, Serra-Majem JL, Bueno-Cavanillas A, Tur JA, Martin Sanchez V, Pinto X, Delgado-Rodriguez M, Matia-Martin P, Vidal J, Vazquez C, Daimiel L, Razquin C, Coltell O, Becerra-Tomas N, De La Torre Fornell R, Abete I, Sorto-Sanchez C, Baron-Lopez FJ, Signes-Pastor AJ, Konieczna J, Garcia-Rios A, Casas R, Gomez-Perez AM, Santos-Lozano JM, Garcia-Arellano A, Guillem-Saiz P, Ni J, Trinidad Soria-Florido M, Zulet MA, Vaquero-Luna J, Toledo E, Fito M, Salas-Salvado J. Mediterranean, DASH, and MIND Dietary Patterns and Cognitive Function: The 2-Year Longitudinal Changes in an Older Spanish Cohort. Front Aging Neurosci. 2021 Dec 13;13:782067. doi: 10.3389/fnagi.2021.782067. eCollection 2021.

  PMID: 34966270 BACKGROUND

• Dickerson BC, Stoub TR, Shah RC, Sperling RA, Killiany RJ, Albert MS, Hyman BT, Blacker D, Detoledo-Morrell L. Alzheimer-signature MRI biomarker predicts AD dementia in cognitively normal adults. Neurology. 2011 Apr 19;76(16):1395-402. doi: 10.1212/WNL.0b013e3182166e96. Epub 2011 Apr 13.

  PMID: 21490323 BACKGROUND

• Skevington SM, Lotfy M, O'Connell KA; WHOQOL Group. The World Health Organization's WHOQOL-BREF quality of life assessment: psychometric properties and results of the international field trial. A report from the WHOQOL group. Qual Life Res. 2004 Mar;13(2):299-310. doi: 10.1023/B:QURE.0000018486.91360.00.

  PMID: 15085902 BACKGROUND

• Ruiz Comellas A, Pera G, Baena Diez JM, Mundet Tuduri X, Alzamora Sas T, Elosua R, Toran Monserrat P, Heras A, Fores Raurell R, Fuste Gamisans M, Fabrega Camprubi M. [Validation of a Spanish Short Version of the Minnesota Leisure Time Physical Activity Questionnaire (VREM)]. Rev Esp Salud Publica. 2012 Oct;86(5):495-508. doi: 10.4321/S1135-57272012000500004. Spanish.

  PMID: 23223762 BACKGROUND

• Matton A, Stephen R, Daniilidou M, Barbera M, Alanko V, Ballin M, Ford J, Hemio K, Lehtisalo J, Rocha SL, Mangialasche F, Ngandu T, Rosenberg A, Saadmaan G, Udeh-Momoh C, Uusimaki K, Solomon A, Kivipelto M. Mechanisms of interventions targeting modifiable factors for dementia risk reduction. Mol Neurodegener. 2025 Jun 23;20(1):75. doi: 10.1186/s13024-025-00845-w.

  PMID: 40551205 BACKGROUND

• Xicota L, Rodriguez-Morato J, Dierssen M, de la Torre R. Potential Role of (-)-Epigallocatechin-3-Gallate (EGCG) in the Secondary Prevention of Alzheimer Disease. Curr Drug Targets. 2017;18(2):174-195. doi: 10.2174/1389450116666150825113655.

  PMID: 26302801 BACKGROUND

• Barbera M, Perera D, Matton A, Mangialasche F, Rosenberg A, Middleton L, Ngandu T, Solomon A, Kivipelto M. Multimodal Precision Prevention - A New Direction in Alzheimer's Disease. J Prev Alzheimers Dis. 2023;10(4):718-728. doi: 10.14283/jpad.2023.114.

  PMID: 37874092 BACKGROUND

• Livingston G, Huntley J, Liu KY, Costafreda SG, Selbaek G, Alladi S, Ames D, Banerjee S, Burns A, Brayne C, Fox NC, Ferri CP, Gitlin LN, Howard R, Kales HC, Kivimaki M, Larson EB, Nakasujja N, Rockwood K, Samus Q, Shirai K, Singh-Manoux A, Schneider LS, Walsh S, Yao Y, Sommerlad A, Mukadam N. Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. Lancet. 2024 Aug 10;404(10452):572-628. doi: 10.1016/S0140-6736(24)01296-0. Epub 2024 Jul 31. No abstract available.

  PMID: 39096926 BACKGROUND

• Frisoni GB, Altomare D, Ribaldi F, Villain N, Brayne C, Mukadam N, Abramowicz M, Barkhof F, Berthier M, Bieler-Aeschlimann M, Blennow K, Brioschi Guevara A, Carrera E, Chetelat G, Csajka C, Demonet JF, Dodich A, Garibotto V, Georges J, Hurst S, Jessen F, Kivipelto M, Llewellyn DJ, McWhirter L, Milne R, Minguillon C, Miniussi C, Molinuevo JL, Nilsson PM, Noyce A, Ranson JM, Grau-Rivera O, Schott JM, Solomon A, Stephen R, van der Flier W, van Duijn C, Vellas B, Visser LNC, Cummings JL, Scheltens P, Ritchie C, Dubois B. Dementia prevention in memory clinics: recommendations from the European task force for brain health services. Lancet Reg Health Eur. 2023 Jan 31;26:100576. doi: 10.1016/j.lanepe.2022.100576. eCollection 2023 Mar.

  PMID: 36895446 BACKGROUND

• Sindi S, Nasholm MS, Barbera M, Thunborg C, Li Y, Jonsson L, Mangialasche F, Qiu C, Kivipelto M. From dementia prevention research to global FINGER-based multi-domain interventions and implementation strategies. Cereb Circ Cogn Behav. 2025 May 30;9:100385. doi: 10.1016/j.cccb.2025.100385. eCollection 2025.

  PMID: 41017958 BACKGROUND

• Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015 Jun 6;385(9984):2255-63. doi: 10.1016/S0140-6736(15)60461-5. Epub 2015 Mar 12.

  PMID: 25771249 BACKGROUND

• Ngandu T, Solomon A, Lehtisalo J, et al. Long-term adherence to lifestyle changes and association with cognitive change: 11-year results from the FINGER randomized, controlled trial. Alzheimers Dement. 2025;21(Suppl 6):e106542. Published 2025 Dec 23. doi:10.1002/alz70860_106542.

  BACKGROUND

• Forcano L, Fauria K, Soldevila-Domenech N, Minguillon C, Lorenzo T, Cuenca-Royo A, Menezes-Cabral S, Pizarro N, Boronat A, Molinuevo JL, de la Torre R; PENSA Study Groupǂ. Prevention of cognitive decline in subjective cognitive decline APOE epsilon4 carriers after EGCG and a multimodal intervention (PENSA): Study design. Alzheimers Dement (N Y). 2021 Mar 31;7(1):e12155. doi: 10.1002/trc2.12155. eCollection 2021.

  PMID: 33816762 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Natàlia Soldevila Domènech, MPH, PhD

CONTACT

(+34) 93 316 09 90; nsoldevila@barcelonabeta.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2026
• First Posted: July 28, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: July 28, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)