MAPT and Stroke: First, it could be that stroke-related events and lacunes are more detrimental for cognitive functioning (compared to e.g. microbleeds), and therefore this effect could represent a survival bias, i.e. individuals that have both stroke-related events and Aβ pathology are less likely to remain cognitively unimpaired.14,49 An alternative explanation is related to the hypothesis that tau spreads via structurally or functionally connected neurons.50,51 It could be that lacunes lead to disrupted brain connectivity, thereby limiting the spread of tau throughout the brain.