Depressive Symptoms Moderate the Influence of the ApolipoproteinE ɛ4 Allele on Cognitive Decline in a Sample of Community Dwelling Older Adults

Abstract

Objectives-The APOE ε4 allele and a history of depression are each separate risk factors for cognitive decline (CD). However, little research has investigated whether a history of depression influences the relationship between APOE ε4 and CD. The present study examined whether depressive symptoms had greater influence on subsequent CD among participants with APOE ε4 than those without the allele. Design-Prospective six year longitudinal study. Setting-Community in-home interviews. Participants-A biracial sample of community dwelling older adults (N=1992) from the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE).Measurements-Data were drawn from Waves 1 and 3 of the EPESE, which were conducted 6 years apart. Cognitive functioning and depressive symptoms were assessed at both waves, and APOE genotyping was completed during the Wave 3 assessment.Results-Regression analyses revealed that depressive symptoms and the APOE ε4 allele independently predicted CD. Importantly, the influence of depressive symptoms on CD was greater for individuals with the APOE ε4 allele compared to those without the allele.Conclusion-Depressive symptoms and the APOE ε4 allele are independent contributors to CD. Moreover, the influence of depressive symptoms on CD is greater among individuals with the APOE ε4 allele. Depression and the APOE ε4 allele may act together in disrupting neurological functioning, which may in turn lower an individual's cognitive reserve capacity. Given the efficacious treatments currently available for depression, future research should investigate the extent to which interventions for depression may reduce the risk for subsequent CD. Keywords APOE; depressive symptoms; cognitive declineCognitive decline (CD) is a significantly increasing problem as individuals age. Mild cognitive impairment affects between 22% and 56% of older adults [1,2], and the prevalence of dementia NIH Public Access Author ManuscriptAm J Geriatr Psychiatry. Author manuscript; available in PMC 2010 February 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript in individuals 65 years and older is approximately 6 to 10%. Further, the prevalence of dementia climbs above 30% among individuals over age 85 [3]. Given the pervasiveness of cognitive impairment in our society, further investigation of factors that influence the onset and course of CD is merited. Identifying such factors may lead to greater insight into ways to prevent or slow the progression of CD. Two variables that have each been individually identified as placing a person at an increased risk for CD are the apolipoproteinE ε4 allele (APOE ε4) and a history of depression or depressive symptoms. APOE ε4 is the most widely recognized genetic risk factor for Alzheimer's disease (AD) [4][5][6]. Nevertheless, other environmental or biological factors are also likely operating to influence CD. In particular, there is growing evidence that a history of depression may increase the risk for CD [7]. Although many studies have exa...

Synergistic associations of depression and apolipoprotein E genotype with incidence of dementia

“…In a cohort of older persons with normal cognitive function, a synergistic interaction was found between depression and APOE e4 on incidence of mild cognitive impairment (Geda et al, 2006). In another cohort with cognitively normal elders, the association between depressive symptoms and cognitive decline was stronger among participants with APOE e4 (Corsentino et al, 2009).…”

Current Versus Lifetime Depression, APOE Variation, and Their Interaction on Cognitive Performance in Younger and Older Adults

“…Carriers of the APOE e4 allele show worse cognitive test performance (3) and increased cognitive decline over time (4)(5)(6). There is mounting evidence to suggest that the effects of depressive symptoms and APOE combine to accelerate cognitive decline in old age (7,8). However, existing studies have been underpowered to investigate this at the genotype level and have focused on depressive symptoms rather than clinically defined depression.…”

Comorbid Depression Is Associated with an Increased Risk of Dementia Diagnosis in Patients with Diabetes: A Prospective Cohort Study

“…2,3 Several studies have reported that depression was associated with faster cognitive decline in carriers of the APOE-ε4 allele, a genetic marker for AD, compared to those without this genetic marker. 5,6 Depression may raise the risk of dementia because of biologic abnormalities associated with this affective illness, such as hypothalamic-pituitary axis dysregulation and high cortisol levels 7 , decreased homeostasis of the autonomic nervous system resulting in decreased heartrate variability 8 , increased platelet activation 9 , and an increase in pro-inflammatory factors. 10 Depression may also increase the risk of dementia because of its association with a higher risk for behavioral risk factors such as smoking, obesity, and sedentary lifestyle and vascular risk factors such as hypertension, hyperlipidemia, and diabetes.…”