The past decades has seen major advances in our understanding of the pathogenesis of dementia and Alzheimer’s disease (AD). Genetic research has uncovered over 40 rare and common genetic variants that play a role in the development of AD. The findings brought to surface various novel protein pathways that drive the development of dementia and yielded new insights in the role of astrocytes and microglia in the aetiology. In parallel, there has been major progress in our knowledge of the non-genetic drivers of dementia and AD in the population. A key feature of the dementia epidemic is the multi-morbidity seen in patients including vascular, endocrine and psychiatric pathology. The seminar discusses the opportunities and challenges for preventive interventions. These include the use of genetic variants to identify high-risk groups in trials and intervention studies and the discovery of blood based biomarkers and predictors of dementia using proteomics and metabolomics. Last but not least, the role of a new player in dementia and neuropsychiatric research, the gut microbiome, will be discussed.