Depressive symptoms and the APOE e4 gene variant are known to be independent risk factors for cognitive decline. Now a prospective study of a large population-based sample of older individuals has found that when a person is not only depressed, but has one or two copies of the APOE e4 gene variant, the risk of cognitive decline is even greater than if he or she had either depression or the variant alone.
The study was headed by Kumar Rajan, Ph.D., an assistant professor at the Rush Institute for Healthy Aging at Rush University Medical Center in Chicago, and the findings were published in the February-March Psychosomatic Medicine.
The study included 4,150 participants aged 65 and older from either an African-American or European background who were interviewed at three-year intervals. Depressive symptoms were measured using the 10-item version of the Center for Epidemiologic Studies Depression scale. The APOE genotype was evaluated by DNA samples collected during follow-up. Cognitive function was evaluated at the initial and follow-up interviews—follow-up was approximately nine years—using a standardized global cognitive score.
About one-third of the cohort had one or more copies of the APOE e4 variant. In participants with no depressive symptoms, cognitive function decreased by 0.0412 unit per year among those with no copies of the APOE e4 variant and 0.0704 unit per year among those with one or more copies of the variant. For each additional symptom of depression, cognitive decline increased by 0.0021 unit per year among those with no copies and 0.0051 unit per year among those with one or more copies of the APOE e4 variant. The three-way interaction of depressive symptoms, the APOE e4 variant, and time was significant.
That is, the researchers found that the deleterious effect of depressive symptoms on cognitive decline was magnified by the presence of the APOE e4 variant.
“This finding has important implications for older adults, health care practitioners, scientists, and public-health experts—further demonstrating the complex interplay of mental health and genetic markers on late-life cognitive health,” Rajan and colleagues concluded.
“Given that our study was based on a population-based sample with a fairly large number of participants being genotyped from two different population structures (European and African American), we feel confident that these results are generalizable and verifiable by other longitudinal population-based studies of older persons.”
In an accompanying editorial, Michelle Luciano, Ph.D., of the Center for Cognitive Aging and Cognitive Epidemiology at the University of Edinburgh, said, “Given that the APOE genotype is fixed in an individual, one of the questions that the research of Rajan et al. raises is the potential to curb cognitive decline through interventions targeting depression.”
The study was funded by the National Institute on Aging. ■
An abstract of “Gene-Behavior Interaction of Depressive Symptoms and the Apolipoprotein e4 Allele on Cognitive Decline” can be accessed
here.
