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Alzheimer's disease (AD) is the most prevalent type of dementia, accounting for 80% of dementia worldwide. It commonly occurs in the elderly population causing a progressive decline of cognitive domains, including attention, learning, memory and planning abilities. Cognitive impairment associated with dementia is a major source of burden, deterioration in life quality, and reduced psychological well-being, in turn resulting in large and increasing social costs. The etiology of AD remains unknown. The diagnosis of dementia is mainly made on a clinical basis, lacking appropriate biomarkers that can provide an unequivocal diagnosis and characterize in vivo the metabolic and microstructural events associated to early disease development. This project will develop and exploit new MRI techniques based on heteronuclear imaging in combination with quantitative MRI to identify potential biomarkers of the disease and to explore the physiopathological processes underlying the microstructural tissue damage and the cognitive deterioration. Sodium has a fundamental role in many physiological and biochemical functions. In particular, sodium homeostasis is associated to neuroinflammation, with potential sensitivity to vascular and metabolic alterations. Currently, no non-invasive MR imaging tools are available to reliably detect subtle neuroinflammation. In this project, we will develop heteronuclear MRI as a tool to investigate neuroinflammation associated with AD, and as a component of a multiparametric quantitative MRI protocol to disentangle, in-vivo and non-invasively, distinct neurophysiological alterations underlying the neuroinflammation. The viability of sodium biomarkers to investigate inflammation and neurodegeneration in patients will be assessed, and the relevant role as a marker of cognitive impairment will be studied. This project is based on a multidisciplinary collaboration including "hard" and "soft" skills of physicists, neurologists, psychologists, and exploiting cutting-edge medical imaging technology. The outcomes of this project have a significant impact potential on clinical research and on clinical practice in terms of new knowledge about neuroinflammation and neurophysiological alterations in AD, and of availability of the relevant neuroimaging tools.