This scientific commentary refers to ‘Relative impact of amyloid-β, lacunes, and downstream imaging markers on cognitive trajectories’, by Kim et al. (doi:10.1093/brain/aww148) . Alzheimer’s disease is the most common cause of dementia in the elderly, with prevalence doubling every 5 years after the age of 65 years. It has been suggested that risks for Alzheimer’s disease and cardiovascular disease may be linked (Launer et al. , 2000). However, the relationship between vascular disease and Alzheimer pathology has not been clearly established (Chui et al. , 2012). Although theoretical mechanisms exist by which vascular disease and Alzheimer pathology might interact, it is also possible that the two processes operate in parallel and are unrelated at a pathological level, interacting only in their clinical effects. In this issue of Brain , Kim and co-workers propose that progression of Alzheimer pathology (measured by amyloid-β PET imaging) or cerebrovascular disease (CVD, measured by the presence of lacunes on MRI) have regionally specific effects on downstream imaging markers, and lead to cognitive decline via …