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Randomized controlled trial on the efficacy of a multilevel non-pharmacologic intervention in older adults with subjective memory decline: design and baseline findings of the E.Mu.N.I. study

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Abstract

Background

Alzheimer’s Disease (AD) is a multifactorial disorder driven by genetic and modifiable lifestyle risk factors. Lifestyle primary prevention initiatives may reduce the prevalence and incidence of dementia in older adults.

Objectives

The E.Mu.N.I study is a randomized controlled trial investigating the effect of multilevel non-pharmacologic interventions on cognitive performances (primary outcome) and structural and vascular brain MRI markers (secondary outcome), as well as markers of brain functional connectivity change (exploratory outcome), in older adults with subjective memory decline (SMD). Here, we present the study design and the baseline features of the sample.

Methods

Cognitively intact older adults with SMD, enrolled between February 2016 and June 2017, were randomly assigned to one of the 3 interventions for 1 year: Active Control Intervention (ACI), i.e., educational lessons; Partial Intervention (PI), i.e., homotaurine administration (100 mg/die) and lessons on the Mediterranean diet; Multilevel Intervention (MI), i.e., PI plus computerized cognitive training and physical exercise training.

Results

One-hundred and twenty-eight eligible participants were enrolled (66% female; age: 68 ± 5 years). Eighty-two percent of the sample was composed of volunteers with SMD from the community. Participants were randomly allocated to the interventions as follows: ACI (N = 40), PI (N = 44), MI (N = 44). No significant differences among groups emerged on socio-demographic, clinical–neuropsychological variables and MRI markers at baseline.

Conclusions

The outcomes obtained from the E.Mu.N.I. study will clarify the efficacy of multilevel non-pharmacologic interventions on cognitive and neuroimaging markers in SMD individuals. This is a crucial step forward for the development of cost-effective non-pharmacologic primary prevention initiatives for AD.

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Acknowledgements

This study was funded by the Italian Ministry of Health (grant number GR-2011-02350494, Bando Giovani Ricercatori 2011-2012). The funding source had no role in the design of the study, data analysis and writing the manuscript. The authors would like to thank FB Health for the supply of Homotaurine (VIVIMIND™), Neocogita Srl for the support with computerized cognitive training program (BrainHQ) and Elena Staffieri for designing and implementing the nutrition guidance course. Harald Hampel is supported by the AXA Research Fund, the “Fondation partenariale Sorbonne Université” and the “Fondation pour la Recherche sur Alzheimer”, Paris, France. Ce travail a bénéficié d’une aide de l’Etat “Investissements d’avenir” ANR-10-IAIHU-06. The research leading to these results has received funding from the program “Investissements d’avenir” ANR-10-IAIHU-06 (Agence Nationale de la Recherche-10-IA Agence Institut Hospitalo-Universitaire-6). This manuscript benefited from the support of the Program “PHOENIX” led by the Sorbonne University Foundation and sponsored by la Fondation pour la Recherche sur Alzheimer.

Author information

Authors and Affiliations

  1. Laboratory of Alzheimer’s Neuroimaging and Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125, Brescia, Italy

    Elena Rolandi, Samantha Galluzzi, Federica Ribaldi, Giulio Munaretto, Giovanni B. Frisoni & Enrica Cavedo

  2. NIMTlab, Neuroimaging and Innovative Molecular Tracers Laboratory, University of Geneva, Geneva, Switzerland

    Alessandra Dodich

  3. Statistics Service, IRCCS Centro San Giovanni di Dio Fatebenefratelli, 25125, Brescia, Italy

    Clarissa Ferrari

  4. Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy

    Sara Mandelli

  5. Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy

    Federica Ribaldi

  6. Department of Diagnostic Imaging, Neuroradiology Unit, University of Brescia, Brescia, Italy

    Claudia Ambrosi & Roberto Gasparotti

  7. Millennium Sport and Fitness, 25124, Brescia, Italy

    Davide Violi

  8. NEtS Center, Scuola Universitaria Superiore IUSS Pavia, 27100, Pavia, Italy

    Nicola Canessa

  9. Cognitive Neuroscience Laboratory, IRCCS ICS Maugeri, 27100, Pavia, Italy

    Nicola Canessa & Chiara Cerami

  10. Department of Clinical Neuroscience, San Raffaele Turro Hospital, 20132, Milan, Italy

    Sandro Iannaccone & Alessandra Marcone

  11. Division of Neuroscience, Department of Neuroradiology and CERMAC, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

    Andrea Falini

  12. Alzheimer Precision Medicine (APM), Établissements Publics à Caractère Scientifique et Technologique (E.P.S.T.), AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University Clinical Research Group (GRC n°21), Boulevard de l’hôpital, 75013, Paris, France

    Harald Hampel & Enrica Cavedo

  13. Brain and Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l’hôpital, 75013, Paris, France

    Harald Hampel & Enrica Cavedo

  14. Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Institute of Memory and Alzheimer’s Disease (IM2A), François Lhermitte Building, 47 Boulevard de l’hôpital, 75013, Paris Cedex 13, France

    Harald Hampel & Enrica Cavedo

  15. Memory Clinic and LANVIE-Laboratory of Neuroimaging of Ageing, University Hospitals and University of Geneva, Geneva, Switzerland

    Federica Ribaldi & Giovanni B. Frisoni

  16. Department of Life Sciences, University of Trieste, Trieste, Italy

    Giulio Munaretto

Authors
  1. Elena Rolandi
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  2. Alessandra Dodich
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  3. Samantha Galluzzi
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  4. Clarissa Ferrari
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  5. Sara Mandelli
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  6. Federica Ribaldi
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  8. Claudia Ambrosi
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  9. Roberto Gasparotti
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  10. Davide Violi
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  18. Enrica Cavedo
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Corresponding author

Correspondence to Enrica Cavedo.

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Conflicts of interest

Dr E Rolandi, A Dodich, S Galluzzi, C Ferrari, S Mandelli, F Ribaldi, G Munaretto, C Ambrosi, R Gasparotti, D Violi, N Canessa, S Iannaccone, A Marcone, A Falini, GB. Frisoni, C Cerami, E Cavedo report no disclosures. H Hampel serves as Senior Associate Editor for the Journal Alzheimer’s & Dementia; he received lecture fees from Biogen and Roche, research grants from Pfizer, Avid, and MSD Avenir (paid to the institution), travel funding from Functional Neuromodulation, Axovant, Eli Lilly and company, Takeda and Zinfandel, GE-Healthcare and Oryzon Genomics, consultancy fees from Jung Diagnostics, Cytox Ltd., Axovant, Anavex, Takeda and Zinfandel, GE Healthcare, Oryzon Genomics, and Functional Neuromodulation, and participated in scientific advisory boards of Functional Neuromodulation, Axovant, Eli Lilly and company, Cytox Ltd., GE Healthcare, Takeda and Zinfandel, Oryzon Genomics and Roche Diagnostics. HH is co-inventor in the following patents as a scientific expert and has received no royalties: In Vitro Multiparameter Determination Method for The Diagnosis and Early Diagnosis of Neurodegenerative Disorders Patent Number: 8916388. In Vitro Procedure for Diagnosis and Early Diagnosis of Neurodegenerative Diseases Patent Number: 8298784. Neurodegenerative Markers for Psychiatric Conditions Publication Number: 20120196300. In Vitro Multiparameter Determination Method for The Diagnosis and Early Diagnosis of Neurodegenerative Disorders Publication Number: 20100062463. In Vitro Method for The Diagnosis and Early Diagnosis of Neurodegenerative Disorders Publication Number: 20100035286. In Vitro Procedure for Diagnosis and Early Diagnosis of Neurodegenerative Diseases Publication Number: 20090263822. In Vitro Method for The Diagnosis of Neurodegenerative Diseases Patent Number: 7547553. CSF Diagnostic in Vitro Method for Diagnosis of Dementias and Neuroinflammatory Diseases Publication Number: 20080206797. In Vitro Method for The Diagnosis of Neurodegenerative Diseases Publication Number: 20080199966. Neurodegenerative Markers for Psychiatric Conditions Publication Number: 20080131921.

Ethical approval

The study was performed in accordance with the guidelines of the Declaration of Helsinki. The study was approved by local ethics committees (Comitato Etico IRCCS San Giovanni di Dio Fatebenefratelli; Comitato Etico di Brescia; Comitato Etico dell’Ospedale San Raffaele).

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Written informed consent was collected for all of the participants.

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Rolandi, E., Dodich, A., Galluzzi, S. et al. Randomized controlled trial on the efficacy of a multilevel non-pharmacologic intervention in older adults with subjective memory decline: design and baseline findings of the E.Mu.N.I. study. Aging Clin Exp Res 32, 817–826 (2020). https://doi.org/10.1007/s40520-019-01403-3

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