UK Biobank is the world's most comprehensive longitudinal population-based data and biosample resource. Twenty years after UK Biobank was first established, the incidence of dementia among participants is rising and is set to increase rapidly over the next 5-10 years, creating a distinct opportunity for studies of dementia risk and onset. In addition to extensive clinical phenotyping of >500,000 volunteers from across the UK at recruitment and at follow-up time points, UK Biobank includes data from serial lifestyle questionnaires, cognitive testing, multimodal imaging, accelerometry, genomics and other omics that are linked to individual health, cancer and death records. In this Perspective, we discuss how the use of UK Biobank data has enabled the discovery of new interactions between systemic and brain health and illustrate how these data can be used to characterize and identify risk factors, support mechanistic hypotheses and identify new biomarkers that predict the onset and course of dementia and related disorders. We also consider future developments of UK Biobank, including the UK Biobank Brain Health Study, which will build on and leverage the increasing incidence of dementias to advance understanding of these conditions.