Exploratory mediation analyses showed the lowest perioperative Hb levels accounted for 55.9% of the effect of anemia on POD, with preoperative transfusions and transfusion volume accounting for 35.4 and 8.7%, respectively.<h4>Conclusion</h4>Severe perioperative anemia is strongly associated with increased POD risk in older adults with ITF, independent of other clinical factors. Here, GSTM1 is linked to anemia (phenotype).