It is clear that the neurodegenerative disease processes which cause dementias are initiated many years before the onset of symptoms. In people with mild cognitive impairment there is already good evidence available to suggest that many of the key pathologies are well established. The PREVENT research programme seeks to understand the origin point and sequence of pathological changes which lead to dementia. It also aims to determine what clinical, environmental and genetic factors increase (or decrease) the risk of these changes initiating and developing. From this data we will be able to develop risk models that can be applied both in clinical practice and research which illustrate the chances a given individual has of developing clinical symptoms of neurodegenerative disease. Once these risks are identified and the sequence of pathological events are characterized; interventions to remove risk or reduce the impact of a risk can be undertaken, as can studies of agents which specifically target the earliest or most up-stream pathological processes. This paper provides the conceptual framework for the PREVENT programme and other similar studies interrogating people in midlife with a view to providing empirical evidence to inform intervention studies and better clinical practice.