As the global population faces a progressive shift towards a higher median age, understanding the mechanisms underlying healthy brain ageing has become of paramount importance for the preservation of cognitive abilities. The first part of the present review aims to provide a comprehensive look at the anatomical changes the healthy brain endures with advanced age, while also summarizing up to date findings on modifiable risk factors to support a healthy ageing process. Subsequently, we describe the typical cognitive profile displayed by healthy older adults, conceptualizing the well-established age-related decline as an impairment of four main cognitive factors and relating them to their neural substrate previously described; different cognitive trajectories displayed by typical Alzheimer's Disease patients and successful agers with a high cognitive reserve are discussed. Finally, potential effective interventions and protective strategies to promote cognitive reserve and defer cognitive decline are reviewed and proposed.