Objectives Studies suggest early onset depression (EOD) is associated with a more severe course of the depressive disorder, while late onset depression (LOD) is associated with more cognitive and neuroimaging changes. This study examined if older adults with EOD, compared with those with LOD, would exhibit more severe symptoms of depression and, consistent with the glucocorticoid cascade hypothesis, have more hippocampal volume loss. A second goal was to determine if LOD, compared with EOD, would demonstrate more cognitive and neuroimaging changes. Method At regular intervals over a four year period non-demented, older, depressed adults were assessed on the Mini Mental Status Examination (MMSE) and the Montgomery-Asberg Depression Rating Scale (MADRS). They were also assessed on Magnetic Resonance Imaging (MRI). Results Compared with LOD, EOD had more depressive symptoms, more suicidal thoughts, and less social support. Growth curve analyses indicated that EOD demonstrated higher levels of residual depressive symptoms over time. The LOD group exhibited a greater decrement in cognitive scores. Contrary to the glucocorticoid cascade hypothesis, participants with EOD lost right hippocampal volume at a slower rate than did participants with LOD. Right cerebrum gray matter was initially smaller among participants with LOD. Conclusions EOD is associated with greater severity of depressive illness. LOD is associated with more severe cognitive and neurological changes. These differences are relevant to understanding cognitive impairment in geriatric depression.

Objective The aim of this study was to develop and test a model of depression, hippocampal changes, and cognitive decline. Method Participants were 248 community-dwelling, depressed patients and 147 healthy, non-depressed individuals 60 years and older. Participants received a structured interview assessing current depressive symptoms and past depressive episodes, completed cognitive testing with the MMSE, and underwent structural MRI of the brain. For up to ten years, assessment of depressive symptoms and MMSE administration was repeated at least annually, and MRI was repeated every two years. Results Regression analyses demonstrated that depression diagnosis at baseline predicted decrease in right (but not left) hippocampal volume over a four-year period. Analyses using structural equation modeling demonstrated that a decrease in left and right hippocampal volume predicted decrease in MMSE score over four years. Conclusion Results provide some evidence for relationships between depression and decrease in right hippocampal volume, and between hippocampal volume and MMSE score. This would be consistent with depression as a causal factor in subsequent cognitive decline. Plausible biological mechanisms include a glucocorticoid cascade or a facilitating effect of depression on amyloid-beta plaque formation. Future studies should examine the relationship between hippocampal volume and specialized memory measures, as well as between depression diagnosis and volume of other brain structures.

Background: Most, but not all, past studies have suggested that the APOE genotype is a risk factor for dementia in whites but not African Americans. This paper first describes explanations as to why some studies may have failed to detect the effect of APOE genotype in African American samples. Briefly, studies have been limited by various methodological problems including small sample sizes, dichotomous measures of cognitive functioning (which tend to be less sensitive to change), and racial bias in assessing demented status. Objective: This paper suggests methods for increasing the likelihood that genuine racial differences will be identified when examining genetic risk factors. Further, we test our model of racial differences in the relationship of APOE genotype and cognitive decline (CD) in a large prospective community sample. Methods: Building on the work of Fillenbaum and colleagues [J Am Geriatr Soc 2001;49:1148–1155], we used data from the Duke EPESE study collected in four waves over a 10-year period (n = 2,076) to illustrate methods which may better assess racial differences in the influence of the APOE ε4 allele on CD. We used multilevel models for repeated measures to examine racial differences in participants’ increase in errors on a continuous measure of cognitive functioning as they aged. Results: We found the APOE ε4 allele to predict CD for both African Americans and whites. Having at least one ε4 allele predicted more cognitive errors at wave 1 and a faster rate of decline for both African Americans and whites over time. While African Americans experienced a faster rate of CD than whites, there was no additional increase in CD from being both African American and a carrier of the ε4 allele. Conclusion: The study points to several common methodological issues that arise when examining racial differences in genetic influences on health-related outcomes. Further, the study’s results highlight the importance of including both African Americans and Caucasians in research concerning the contribution of APOE genotype to CD.

The negative effects of childhood abuse persist for many years, even into older adulthood. However, contrary to the findings in younger adults, self-esteem was not correlated with childhood abuse in older adults. Moreover, childhood abuse only had a negative effect on those who had low self-esteem. It may be through the process of lifespan development that some abused individuals come to separate out the effects of abuse from their self-concept.

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...