APOE and Alzheimer disease: These synergistic effects can drastically compound the damaging effects of WMH in APOE ε4 carriers.41 Faster WMH progression rates were noted in APOE ε4–positive patients with AD and healthy adults, supporting our interaction hypothesis.38,42APOE ε4 carriers might also have more covert white matter damage that is not detected by routine imaging,43 but is reflected as worse cognitive outcomes.