Aims: We investigated if APOE4 carrier status modifies the effect of depression on the risk of dementia.
Methods: Subjects were 1933 Japanese-American men [mean age: 76.3 (SD: 3.6)] participating in the Honolulu-Asia Aging Study (HAAS) and followed for approximately 7 years. Study participants were screened for depressive symptoms by using an 11-item version of the Centers for Epidemiologic Studies Depression Scale (CES-D) at baseline exam. Dementia cases were examined by a neurologist or geriatrician and diagnosed using international criteria. Hazard ratios (HR) for the incidence of dementia were estimated using Cox proportional hazards models adjusted for age, education, stroke history, cardiovascular risk factors. Participants were divided into 4 groups based on depression status at baseline and APOE e4 carrier status: men without depression and without APOE e4, men without depression and with APOE e4, depressed men without APOE e4, depressed men with APOE e4.
Results: Compared to men with neither APOE e4 nor depression, depressed men without APOE e4 had 1.8 fold greater risk [95% CI (CI): 0.9–3.4], while depressed men with APOE e4 had 7.4 times greater risk (CI: 3.2–17.4). The risk in non-depressed men with APOE e4 for dementia was not statistically significant, although it was consistent with an increasing risk for dementia across the 4 strata from the men with neither depression nor APOE e4 to the strata with both depression and APOE e4.
Conclusions: APOE status modifies the association between depression and dementia. Whether aggressive efforts in treating depression in men with APOE e4 can reduce the risk of dementia warrants consideration.
