Longitudinal mixed effects and mediation models examined the sex differences across cognitive decline trajectories of amyloid (A), tau (T), and neurodegeneration (N) groups.<h4>Results</h4>A<sup>+</sup>T<sup>-</sup> males showed faster cognitive decline compared to A<sup>+</sup>T<sup>-</sup> females (p < 0.005), whereas A<sup>+</sup>T<sup>+</sup> females showed steeper cognitive decline compared to A<sup>+</sup>T<sup>+</sup> males (p < 0.0001). This evidence concerns the gene MAPT and Mental deterioration.