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

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.

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