In addition, sex marginally moderated the mediating effect of tau on the relationship between amyloid and cognitive decline (p = 0.046).<h4>Discussion</h4>Sex differences in vulnerability to tau pathology in the presence of amyloid can shape cognitive decline trajectories.<h4>Highlights</h4>A<sup>+</sup>T<sup>-</sup> males showed faster cognitive decline compared to A<sup>+</sup>T<sup>-</sup> females. Here, MAPT is linked to Mental deterioration.