We followed an expert-proposed framework combining epidemiologic and toxicological evidence to make causal inference,55 focusing on the comparison of PM effect sizes, rather than the interaction P-value, which can be misleading.56 The adverse effects of high ambient PM2.5 on global cognitive decline and dementia risk were several fold greater in APOE ɛ4/4 than ɛ3/3 carriers. The gene discussed is APOE; the disease is dementia.