We found significant worsening of PI performance after removal of the distal orientation cues (return condition three) across all individuals with elevated AD risk; namely, both a main effect of CAIDE (F1,77 = 11.04, P = 0.001; Pearson's r = 0.30, P = 0.003; Figure 1B) and two‐way interaction effect of family history and APOE ε4 status (F1,77 = 8.43, P = 0.005; hereditary x physiological interactions all P > 0.303). The gene discussed is APOE; the disease is Alzheimer disease.