EMuNI Project: Multiple Nonpharmacological Interventions
Condition: Lifestyle Risk Reduction
Study type: Interventional

Summary: 
      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: 
      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.
    

Intervention name(s): Nutritional supplementation; Educational training; Counselling on a brain-healthy diet; Physical exercise training; Computerized cognitive training
Intervention type(s): Dietary Supplement; Behavioral; Behavioral; Behavioral; Behavioral
Intervention description(s): Daily consumption of Tramiprosate (100 mg) for 1 year; 16 educational lessons (twice a week): basic principles of different cognitive domains (e.g. memory, attention, perception) and educational DVD viewing.; 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.; 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; 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).
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: primary prevention; Subjective Cognitive Decline; Neuroimaging; Alzheimer's disease; nonpharmacological interventions; multidomain lifestyle interventions