Apolipoprotein epsilon4 allele status, depressive symptoms, and cognitive decline in middle-aged and elderly persons without dementia.

OBJECTIVE: Because the apolipoprotein epsilon4 (APOE-epsilon4) allele or depressive symptoms may increase the risk for development of Alzheimer disease (AD), the authors assessed APOE-epsilon4 status, baseline level of depressive symptoms, and subsequent cognitive decline in middle-aged and older persons without dementia. METHODS: The 49 subjects (age range: 51-85 years) included 20 with and 29 without APOE-epsilon4. Baseline and follow-up neuropsychological assessments determined the degree of cognitive decline. RESULTS: Baseline mild depressive symptoms were greater in APOE-epsilon4 carriers than in non-carriers. The subject groups demonstrated significant cognitive decline at follow-up. APOE-epsilon4 carriers showed a significantly greater rate of verbal memory decline than non-carriers. Baseline depressive symptoms, however, did not predict future cognitive decline. CONCLUSIONS: These results suggest that APOE-epsilon4 carriers may have a greater severity of depressive symptoms than non-carriers. The APOE-epsilon4 allele (but not baseline mild depressive symptoms) is associated with verbal memory decline in middle-aged and older persons. Because of the limited range of depression scores in our sample, these findings should be interpreted with caution and not be generalized to patients with syndromal depression.