The joint effects of APOE4 and high school education or less (HR 2.25, 95% CI: 1.40–3.60, p < 0.001), hypertension (HR 2.46, 95% CI: 1.28–4.73, p = 0.007), elevated depressive symptoms (HR 5.09, 95% CI: 2.59–10.02, p < 0.001), hearing loss (HR 3.44, 95% CI: 1.87–6.33, p < 0.0001), vision impairment (HR 5.14, 95% CI: 2.31–11.43, p < 0.001), smoking (HR 2.35, 95% CI: 1.24–4.47, p = 0.009), or obesity (HR 3.80, 95% CI: 2.11–6.85, p < 0.001) were associated with the hazard of incident CIND (compared to no genetic or modifiable risk factor) in separate models. The gene discussed is APOE; the disease is Obesity.