The increasing aging demographics never seen before is associated with the enormous challenge of dementia epidemics which urgently needs a paradigm shift in the approach to cognitive functions in health and disease. If on one hand the achievement or maintenance of a healthy lifestyle should be a medical priority, the early recognition of cognitive disturbances is mandatory. Cognitive impairment is not only associated with disability and lack of compliance and adherence, but also with dangerous geriatric syndromes such as instability, falls, and delirium. The evaluation of cognitive performance, particularly in older patients and especially in those hospitalized for other reasons, should be performed in all cases. While the National Institute of Aging and Alzheimer Association established new criteria for the diagnosis of Alzheimer's disease, the large majority of dementia cases are assigned to a multifactorial syndrome presenting as a long-lasting continuum from organ/function integrity to dementia. While the monoclonal antibody aducanumab is under careful evaluation for release on the market as the first curative drug, current anti-Alzheimer medication strategies remain symptomatic. In spite of the previous distinction between neurodegenerative and vascular forms of dementia, it is now accepted that control of vascular risk factors and comorbidities strongly affects the prevention of all types of cognitive impairment. The WHO has published in May 2019 an official guideline document for reducing dementia risk. The guidelines provide recommendations on the major modifiable lifestyle factors and chronic diseases. The best way to prevent cognitive impairment and its worsening include vascular risk control and a healthy diet including a balanced natural nutrition (without nutritional supplements for which scientific evidence is lacking), physical exercise (preferably aerobic), enough social participation, interaction and conviviality as well as cognitive exercise (focusing on general cognitive function, executive function and working memory) While the activation of all domains of lifestyle are critical for the achievement of the best preventive effects, these should be implemented 1) in a personalized, goal-oriented fashion (the so called tailored interventions) and 2) with the ultimate goal of maintaining the care of personal interests and functions along with quality of life and wellbeing.For an effective prevention of cognitive decline, resources from all domains of lifestyle (nutrition, exercise, rest, social participation, cognitive activity) should be used, however in a personalized way. The Comprehensive Geriatric Assessment (CGA), evaluating the physical, psychosocial and functional aspects of young-old, old-old and oldest-old persons, can be used to detect early cognitive impairment and factors associated with its course in order to modulate them.