The concept of brain reserve refers to the ability to tolerate the age-related changes and the disease related pathology in the brain without developing clear clinical symptoms or signs. A considerable body of biological research has documented that a number of factors including education, work complexity, social network, and leisure activities may contribute to this reserve allowing cognitive function to be maintained in old ages. Epidemiological studies have also related these factors to the development of dementia, suggesting that intellectual challenges experienced across the whole life span may increase the brain reserve and be crucial for the occurrence of dementia symptoms in late life. This paper is a systematic review of the published epidemiological studies on this topic. The availability of numerous epidemiological and biological data investigating the reserve hypothesis in dementia permits some preliminary conclusions. High education, adult-life occupational work complexity, as well as a mentally and socially integrated lifestyle in late life could postpone the onset of clinical dementia and AD. The relevance of physical activity itself remains in debate, as most physical activities include also social and mental stimulation. Leisure activities with all three components--physical, mental and social--seem to have the most beneficial effect. Delaying dementia onset by five years would halve dementia prevalence and substantially decrease the number of dementia cases in the community.