EMuNI Project: Multiple Nonpharmacological Interventions

Study Overview
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Brief Summary
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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

Detailed Description
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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 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. 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. 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.

Official Title
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Efficacy of Multiple Nonpharmacological Interventions in Individuals With Subjective Memory Complaints

Conditions
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Lifestyle Risk Reduction

Intervention / Treatment
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* Dietary Supplement: Nutritional supplementation
* Behavioral: Educational training
* Behavioral: Counselling on a brain-healthy diet
* Behavioral: Physical exercise training
* Behavioral: Computerized cognitive training


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: No Treatment (NT)<br>Educational training | Behavioral: Educational training<br>* 16 educational lessons (twice a week): basic principles of different cognitive domains (e.g. memory, attention, perception) and educational DVD viewing.<br>|
| Experimental: Partial Treatment (PT)<br>Nutritional supplementation & Counselling on a brain-healthy diet | Dietary Supplement: Nutritional supplementation<br>* Daily consumption of Tramiprosate (100 mg) for 1 year<br>Behavioral: Counselling on a brain-healthy diet<br>* 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.<br>|
| Experimental: Full Treatment (FT)<br>Nutritional supplementation & Counselling on a brain-healthy diet & Physical exercise training & Computerized cognitive training | Dietary Supplement: Nutritional supplementation<br>* Daily consumption of Tramiprosate (100 mg) for 1 year<br>Behavioral: Counselling on a brain-healthy diet<br>* 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.<br>Behavioral: Physical exercise training<br>* 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<br>Behavioral: Computerized cognitive training<br>* 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).<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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primary prevention, Subjective Cognitive Decline, Neuroimaging, Alzheimer's disease, nonpharmacological interventions, multidomain lifestyle interventions