Second, impaired PI was observed in at‐risk individuals across a variety of different risk factors for AD, indicating that the effect is not specific to any individual risk factor—such as APOE ε4—or the underlying physiological mechanism causing the specific risk, but is a general effect, in turn raising the possibility that impaired PI may represent the inflection point in the AD trajectory from at‐risk status to disease onset. Here, APOE is linked to Alzheimer disease.