Support for this hypothesis has been demonstrated in a range of previous studies investigating associations between lifestyle risk and dementia when stratifying either by APOE4 carrier status43,44 or wider polygenic risk for AD.8 Together with the current findings, these studies suggest that lifestyle-related benefits observed in studies of all-cause dementia may instead largely stem from the prevention of vascular-related or mixed dementia pathologies, rather than Alzheimer’s dementia per se. This evidence concerns the gene APOE and Alzheimer disease.