Abstract Background Developed countries are experiencing an unprecedented increase in life expectancy that is accompanied by a tremendous rise in the number of people with dementia. The purpose of this paper is to report on the study design and methodology of an Italian population-based study on brain aging and dementia in the elderly. This multi-domain study is structured in two phases. Our goal is to gather sufficient data to estimate the prevalence (phase I: cross-sectional study), the incidence and the progression of dementia and its subtypes as well as cognitive impairment (phase II: follow-up study) and to identify socio-demographic, clinical, and lifestyle factors associated with dementia and the quality of brain aging in people aged 70–74 years, a crucial point between late adulthood and old age. Methods/Design We chose to contact all 1773 people born between 1935–39 residing in Abbiategrasso, Milan, Italy. Those who agreed to participate in the “Invece.Ab” study were enrolled in a cross-sectional assessment and will be contacted two and four years after the initial data collection to participate in the longitudinal survey. Both the cross-sectional and longitudinal assessments include a medical evaluation, a neuropsychological test battery, several anthropometric measurements, a social and lifestyle interview, blood analyses, and the storage of a blood sample for the evaluation of putative biological markers. Discussion Now at the end of the recruitment phase, the evaluable population has amounted to 1644 people. Among these, 1321 (80.35%) of the participants have completed phase I. This high return rate was likely due to the style of recruitment and personalization of the contacts. Trial registration NCT01345110