EMuNI Project: Multiple Nonpharmacological Interventions (EMuNI)

Efficacy of Multiple Nonpharmacological Interventions in Individuals With Subjective Memory Complaints

By 2030, the global prevalence of Alzheimer's Disease (AD) is predicted to reach 65.7 million worldwide. Despite extensive research efforts, a cure for AD has not been identified. Recent studies on non-demented individuals have demonstrated the importance of a healthy lifestyle (physical exercise, healthy diet) and non pharmacological interventions (diet supplements) to delay the onset of the cognitive decline (Vemuri P et al., 2012). Given that AD is a multi-factorial disorder, some multi- component interventions at early stages could be the best strategy currently available to delay the AD onset. The aim of this study is to investigate the effects of combined non-pharmacological interventions, at different levels of intensity, on cognitive performance, on basic (hippocampal, brain ventricle volumes and white matter lesions) and advanced magnetic resonance imaging (MRI) markers (Resting-state Functional MRI, Probabilistic Diffusion Tensor Tractography

Study Overview

• Status: Completed
• Conditions: Lifestyle Risk Reduction
• Intervention / Treatment: Behavioral: Educational training; Dietary supplement: Nutritional supplementation; Behavioral: Counselling on a brain-healthy diet; Behavioral: Physical exercise training; Behavioral: Computerized cognitive training

Detailed Description

BACKGROUND Recent evidence showed that aerobic exercise, dietary habits and nutritional supplements consumption seem essential for maintaining good cognitive performances increasing hippocampal volume (HV) in healthy elderly people (Erickson et al., 2011; Bowman et al., 2012). Computerized cognitive trainings are effective in improving cognitive functions of healthy older adults (Lampit et al., 2014). Subjective memory complaint (SMC) individuals showed HV, white matter lesions (WML) and brain ventricle volumes (BVV) at limits of normative population (Cavedo et al., 2012) supporting the hypothesis that they are persons at risk of AD (Sperling et al., 2011). The above non-pharmacological treatments, when separately applied, do not impact on cognition and neuropathological processes of AD. On the contrary, combined treatments, in persons at risk to develop AD, could represent the first line of intervention to delay the onset of cognitive impairment.

SPECIFIC AIMS

1. To investigate the combined effect of aerobic exercise, dietary habits, nutritional supplements, and cognitive training administered at three different levels of intensity on cognitive performance in subjective memory complaints individuals. The three different intensity levels of nonpharmacological treatments will be organized as follows: (i) No Treatment (NT) will include educational training (sham condition); (ii) Partial Treatment (PT) will include exclusively the consumption of a nutritional supplement and a training for a balanced diet; (iii) Full treatment (FT) will include all above condition plus computerized cognitive training (no sham condition) and aerobic fitness training.
2. To investigate the effect of the above treatments (NT, PT, FT) on basic markers of magnetic resonance imaging (MRI) such as HV, WML and Brain Ventricle Volume (BVV) in subjective memory complaints individuals.
3. To investigate the effect of NT, PT and FT on advanced MRI markers such as structural brain connectivity and brain resting networks in subjective memory complaints individuals.

HYPHOTESIS AND SIGNIFICANCE An improvement in cognitive performances, basic (HV, WML, BVV) and advanced (structural brain connectivity and brain resting networks) MRI markers will be expected in FT group compared to NT group. Moreover, the investigators hypothesize an effect dependent of the number of combined treatments, thus the PT group is expected to show intermediate results (among NT and FT groups) in the cognitive performances, basic and advanced MRI markers previously described.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Brescia, Italy, 25125
    • IRCCS Centro San Giovanni di Dio Fatebenefratelli
  • Milan, Italy, 20132
    • Ospedale San Raffaele

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age between 60 and 80 years;
• presence of memory complaints

Exclusion Criteria:

• objective cognitive impairment on standard neuropsychological testing;
• history of psychiatric disorders or current clinically relevant depressive or anxious symptoms;
• pacemakers, cochlear implant, metal inserts in the head or shoulders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: No Treatment (NT); Educational training	Behavioral: Educational training; 16 educational lessons (twice a week): basic principles of different cognitive domains (e.g. memory, attention, perception) and educational DVD viewing.
Experimental: Partial Treatment (PT); Nutritional supplementation & Counselling on a brain-healthy diet	Dietary supplement: Nutritional supplementation; Daily consumption of Tramiprosate (100 mg) for 1 year; Behavioral: Counselling on a brain-healthy diet; 4 lessons on the principles of Mediterranean Diet lead by a nutritionist, aimed to teach how to include brain-healthy foods in daily diet (e.g. antioxidant, omega-3 fatty acids and vitamins). Each participant will receive the educational material presented.
Experimental: Full Treatment (FT); Nutritional supplementation & Counselling on a brain-healthy diet & Physical exercise training & Computerized cognitive training	Dietary supplement: Nutritional supplementation; Daily consumption of Tramiprosate (100 mg) for 1 year; Behavioral: Counselling on a brain-healthy diet; 4 lessons on the principles of Mediterranean Diet lead by a nutritionist, aimed to teach how to include brain-healthy foods in daily diet (e.g. antioxidant, omega-3 fatty acids and vitamins). Each participant will receive the educational material presented.; Behavioral: Physical exercise training; 80 sessions of physical exercise supervised by a Fitness Training Expert with the aim of achieving 150 minutes of moderate-intensity physical activity per week; Behavioral: Computerized cognitive training; 16 cognitive training sessions (twice a week) supervised by a psychologist, aimed to improve Attention, Processing speed, Memory, Social skills and Intelligence using BrainHQ (www.brainhq.com).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive functions	Neuropsychological test performances	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Basic imaging marker 1	Hippocampal volumes	12 months
Basic imaging marker 2	White matter hyperintensities volumes	12 months
Basic imaging marker 3	Brain ventricle volumes	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Advanced imaging marker 1	Structural brain connectivity	12 months
Advanced imaging marker 2	Functional networks connectivity at rest	12 months

Collaborators and Investigators

• Sponsor: IRCCS Centro San Giovanni di Dio Fatebenefratelli
• Collaborators: Ospedale San Raffaele; Istituto Di Ricerche Farmacologiche Mario Negri
• Investigators: Principal Investigator: Enrica Cavedo, PhD, IRCCS Centro San Giovanni di Dio Fatebenefratelli

Publications and helpful links

General Publications

• Lampit A, Hallock H, Valenzuela M. Computerized cognitive training in cognitively healthy older adults: a systematic review and meta-analysis of effect modifiers. PLoS Med. 2014 Nov 18;11(11):e1001756. doi: 10.1371/journal.pmed.1001756. eCollection 2014 Nov.
• Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):280-92. doi: 10.1016/j.jalz.2011.03.003. Epub 2011 Apr 21.
• Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):3017-22. doi: 10.1073/pnas.1015950108. Epub 2011 Jan 31.
• Bowman GL, Silbert LC, Howieson D, Dodge HH, Traber MG, Frei B, Kaye JA, Shannon J, Quinn JF. Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging. Neurology. 2012 Jan 24;78(4):241-9. doi: 10.1212/WNL.0b013e3182436598. Epub 2011 Dec 28.
• Cavedo E, Galluzzi S, Pievani M, Boccardi M, Frisoni GB. Norms for imaging markers of brain reserve. J Alzheimers Dis. 2012;31(3):623-33. doi: 10.3233/JAD-2012-111817.
• Vemuri P, Lesnick TG, Przybelski SA, Knopman DS, Roberts RO, Lowe VJ, Kantarci K, Senjem ML, Gunter JL, Boeve BF, Petersen RC, Jack CR Jr. Effect of lifestyle activities on Alzheimer disease biomarkers and cognition. Ann Neurol. 2012 Nov;72(5):730-8. doi: 10.1002/ana.23665.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: December 9, 2017
• First Submitted That Met QC Criteria: December 18, 2017
• First Posted (Actual): December 22, 2017

Study Record Updates

• Last Update Posted (Actual): September 14, 2021
• Last Update Submitted That Met QC Criteria: September 13, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Alzheimer's disease; primary prevention; Neuroimaging; Subjective Cognitive Decline; nonpharmacological interventions; multidomain lifestyle interventions
• Other Study ID Numbers: GR-2011-02350494

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No