Multidimensional intervention (MT) on at-risk for Alzheimer's patients

The first primary goal of this project is to apply a Multidimensional Training (MT) program structured on the best set of activities that increase levels of brain plasticity in the demographic expected to receive the most benefit from it: at-risks for dementia (ARD) subjects who are showing early and subtle signs of cognitive decline (SDC). A primary emphasis of the project concerns the selection of ARD-SCD subjects by using a diagnostic matrix that combines clinical, neuroimaging, neuropsychological, Virtual Reality-(VR) based approaches, and “omics” markers. The array will be used to select individuals suitable for MT as well as a valid surrogate measure to assess the validity of treatment. A crucial point of the proposal revolves around the use of highly standardized sets of training activities. For exercise training (ET) we will employ machines operated by personalized USB keys and allow the activities to be logged, thereby generating individual data files containing all the parameters concerning exercise difficulty, length, compliance to programs, strength, and metabolic consumption. The exercise setting will take advantage of a VR environment. Similarly, for cognitive training (CT) we will employ VR-based rehabilitative software. The application will generate individual data files containing all the parameters concerning the stimulated cognitive domain, difficulty, length, and compliance. The goal is to provide a standardized set of training activities that can be monitored for quantity, quality, and patient compliance. The intervention will include monitoring and intervention of lifestyle-related comorbidity factors (blood pressure, weight and BMI, and hip and waist circumference, diet, smoke). All the data concerning the performed activities will go to a central website, a cloud, and be available for detailed analysis. In the trained group we will also, as recently done in a sizeable preventative cohort study (1), add intervention focused on nutritional status as well as management of metabolic and vascular risk factors. The second primary goal of the project is to investigate the neural and molecular effects of MT. Brain structural and functional MT effects will be investigated with MRI. Molecular MT effects will be evaluated as changes in protein, metabolic biomarkers that have been recently associated with the progression of aging and AD-related cognitive decline (2–4). We will also investigate how genetic differences of key plasticity factors may contribute to the variability of individual responses to training.

Key words:

Brain Aging, fMRI, neuroimaging, cognitive enhancement, Dementia, exercise, neuroprotection, wellness.