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Apolipoprotein 4 Allele Status, Depressive Symptoms, and Cognitive Decline in Middle-Aged and Elderly Persons Without Dementia

Received June 5, 2002; revised August 10, September 6, 2002; accepted September 16, 2002.
From the Department of Psychiatry and Biobehavioral Sciences, the Alzheimer's Disease Center, the Center on Aging, University of California, Los Angeles. Send correspondence to Helen Lavretsky, M.D., UCLA-Neuropsychiatric Institute and Hospital, 760 Westwood Pl., Rm. 37-425, Los Angeles, CA 90095. e-mail: hlavrets{at}ucla.edu

Objective: Because the apolipoprotein 4 (APOE-4) allele or depressive symptoms may increase the risk for development of Alzheimer disease (AD), the authors assessed APOE-4 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-4. Baseline and follow-up neuropsychological assessments determined the degree of cognitive decline. Results: Baseline mild depressive symptoms were greater in APOE-4 carriers than in non-carriers. The subject groups demonstrated significant cognitive decline at follow-up. APOE-4 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-4 carriers may have a greater severity of depressive symptoms than non-carriers. The APOE-4 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.

Key Words: Apolipoprotein-E • Depression • Cognitive Decline