Kathryn Sawyer

Depression, hippocampal volume changes, and cognitive decline in a clinical sample of older depressed outpatients and non-depressed controls

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 Mini Mental State Examination (MMSE), and underwent structural Magnetic Resonance Imaging (MRI) of the brain. For up to 10 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 volumes 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.

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

OBJECTIVES The apolipoproteinE epsilon4 (APOE epsilon4) 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 epsilon4 and CD. The present study examined whether depressive symptoms had greater influence on subsequent CD among participants with APOE epsilon4 than those without the allele. DESIGN Prospective 6-year longitudinal study. SETTING Community in-home interviews. PARTICIPANTS A biracial sample of community dwelling older adults (N = 1,992) from the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE). MEASUREMENTS Data were drawn from Waves 1 to 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 epsilon4 allele independently predicted CD. Importantly, the influence of depressive symptoms on CD was greater for individuals with the APOE epsilon4 allele compared with those without the allele. CONCLUSION Depressive symptoms and the APOE epsilon4 allele are independent contributors to CD. Moreover, the influence of depressive symptoms on CD is greater among individuals with the APOE epsilon4 allele. Depression and the APOE epsilon4 allele may act together in disrupting neurological functioning, which may in turn lower an individuals 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.

A longitudinal study of differences in late- and early-onset geriatric depression: depressive symptoms and psychosocial, cognitive, and neurological functioning.

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 and the Montgomery–Asberg Depression Rating Scale. They were also assessed on magnetic resonance imaging. 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.

The long-term impact of childhood abuse on internalizing disorders among older adults: The moderating role of self-esteem

Objectives: First, to determine if childhood experiences of abuse have an impact on internalizing disorders (e.g., anxiety and depressive disorders) among older adults. Second, we wish to determine if self-esteem plays a role in explaining the relationship between abuse and internalizing disorders. Method: First, we conducted an analysis on a population sample of participants aged 50 years or older (mean age = 67 years; SD = 10.3) assessed at two time points, three years apart (Wave 1, N = 1460; Wave 2, N = 1090). We examined the relationship between reports of childhood abuse (physical, emotional, and sexual) and internalizing disorders. Second, we determined the role self-esteem played in explaining the relationship. Results: We found that childhood experiences of abuse assessed at Wave 1 predicted the number of DSM-IV internalizing disorders occurring three years later. Demonstrating the specificity of self-esteem; we found self-esteem, but not emotional reliance, to moderate the relationship between abuse and internalizing disorders such that childhood abuse had more negative effects on those with low self-esteem compared to those with higher self-esteem. Contrary to prediction, self-esteem did not mediate the relationship between abuse and internalizing disorders. Conclusion: 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.

Comorbidity of Pain and Depression Among Persons With Traumatic Brain Injury

OBJECTIVE To assess the prevalence of pain, depression, and comorbid pain and depression among a civilian sample of persons with traumatic brain injury (TBI). DESIGN Longitudinal survey design with 1-year follow-up. SETTING Inpatient rehabilitation and the community. PARTICIPANTS Participants (N=158) admitted to inpatient rehabilitation after moderate to severe TBI. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Depression was assessed with the Patient Health Questionnaire-9 (PHQ-9); pain was assessed with a numerical rating scale from 0 (no pain) to 10 (worst pain). Participants who reported average pain ≥ 4 were classified as having pain, and participants with PHQ-9 scores ≥ 10 were classified as depressed. RESULTS Both pain and depression were more prevalent at baseline assessment (pain: 70%; depression: 31%) than at year 1 (pain: 34%; depression: 22%). Comorbid pain and depression declined from 27% at baseline to 18% at year 1. Pain was significantly associated with depression at baseline (relative risk: 2.62, P=.003) and at year 1 (relative risk: 7.98, P<.001). CONCLUSIONS Pain and depression are common and frequently co-occur in persons with TBI. Although their frequency declined over the first year after injury, the strength of their association increased. Assessment and treatment of both conditions simultaneously may lead to improved outcomes, both early after TBI and over time.

Racial differences in the influence of the APOE epsilon 4 allele on cognitive decline in a sample of community-dwelling older adults.

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.

Longitudinal Study of Headache Trajectories in the Year After Mild Traumatic Brain Injury: Relation to Posttraumatic Stress Disorder Symptoms

OBJECTIVE: To examine headache trajectories among persons with mild Traumatic Brain Injury (mTBI) in the year following injury, and the relationship of headache trajectory to PTSD at one year post injury. DESIGN: Prospective, Longitudinal study SETTING: Participants were recruited through a university medical center and participated in follow-up assessments by telephone. PARTICIPANTS: 212 prospectively enrolled individuals within one week of mTBI who were hospitalized for observation or other system injuries. Participants were assessed at baseline, three, six, and twelve months post-injury. INTERVENTIONS: Not applicable MAIN OUTCOME MEASURES: Participants rated average headache pain intensity using the 0-10 numeric rating scale at each assessment period. The PTSD Checklist - Civilian Version (PCL-C) was completed at twelve months post-injury. RESULTS: Latent Class Growth Analysis produced a four trajectory group model, with groups labeled Resolved, Worsening, Improving, and Chronic. Multivariate regression modeling revealed that younger age and premorbid headache correlated with membership in worse trajectory groups (Worsening and Chronic; pCONCLUSIONS: Headache is common in the year following mTBI, with younger people, persons who previously had headaches, and persons with PTSD more likely to report Chronic or Worsening headache. Further research is needed to examine whether PTSD symptoms exacerbate headaches, or whether problematic headache symptoms exacerbate PTSD. Language: enOBJECTIVE To examine headache trajectories among persons with mild traumatic brain injury (MTBI) in the year after injury and the relation of headache trajectory to posttraumatic stress disorder (PTSD) at 1 year postinjury. DESIGN Prospective, longitudinal study. SETTING Participants were recruited through a university medical center and participated in follow-up assessments by telephone. PARTICIPANTS Prospectively enrolled individuals (N=212) within 1 week of MTBI who were hospitalized for observation or other system injuries. Participants were assessed at baseline and 3, 6, and 12 months postinjury. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Participants rated average headache pain intensity using the 0 to 10 numerical rating scale at each assessment period. The PTSD Checklist-Civilian Version was completed at 12 months postinjury. RESULTS Latent class growth analysis produced a 4-trajectory group model, with groups labeled resolved, worsening, improving, and chronic. Multivariate regression modeling revealed that younger age and premorbid headache correlated with membership in the worse trajectory groups (worsening and chronic; P<.001). Univariate regression revealed a significant association between PTSD and membership in the worse trajectory groups (P<.001). CONCLUSIONS Headache is common in the year after MTBI, with younger people, persons who previously had headaches, and persons with PTSD more likely to report chronic or worsening headache. Further research is needed to examine whether PTSD symptoms exacerbate headaches or whether problematic headache symptoms exacerbate PTSD.

APOE ϵ4 allele carriers: Biological, psychological, and social variables associated with cognitive impairment

Objective: The apolipoprotein (APOE) ε4 allele genotype is a risk factor for dementia, but not all people with the APOE ε4 allele develop cognitive impairment (CI). Among participants with the APOE ε4 allele (N = 664), we identified biological, psychological, and social variables that discriminate between participants who develop CI from those who do not. We then determined if these variables predicted CI in noncarriers (N = 1421). In the sample as a whole we then determined if each of these identified variables moderate the relationship between the APOE ε4 allele and CI. Methods: We used data from a biracial community-dwelling sample of older adults. Data were collected at four time points over a 10-year period. Cognitive functioning was assessed at each wave, using the Short Portable Mental Status Questionnaire (SPMSQ). APOE genotyping was performed at Wave 3. Results: Among APOE ε4 allele carriers, but not noncarriers, variables associated with CI included white race, female gender, low BMI, number of negative life events, and health problems (high blood pressure, heart disease, and stroke). In analyses testing for moderate effects and including the entire sample, significant interactions with APOE ε4 allele and predictor variables revealed that white race, low BMI, stroke, heart disease, and negative life events had a greater effect on CI among those with the APOE ε4 allele compared to those without the allele. Conclusion: There are biological, psychological, and social variables associated with increased risk for CI among individuals with the APOE ε4 allele.

Problems meeting basic needs moderate the association between the APOE ϵ4 allele and cognitive decline

Objectives: The ApolipoproteinE ε4 (APOE ε4) allele influences cognitive decline (CD) in some but not in all individuals. The purpose of this study was to investigate whether problems meeting basic needs (BN) (e.g., having enough money to meet needs, having enough money for emergencies, having adequate housing, and having enough heat) influences the relationship between the APOE ε4 allele and CD. We predicted that problems meeting BN would have a greater influence on CD among those with the APOE ε4 allele than those without the allele. Methods: Participants consisted of community-dwelling older adults from the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE). Data were drawn from Waves 1 and 2, which were 3 years apart. Cognitive functioning was assessed at both waves so that change in cognitive status was examined over time, and cognitive status was controlled at baseline. Genotyping, however, was not obtained until Wave 3. Results: The APOE ε4 allele and problems meeting BN independently predicted CD. Importantly, the influence of BN on CD was greater for individuals with the APOE ε4 allele compared to those without the allele. Other indicators of socioeconomic status (e.g., education, income) did not interact with the APOE ε4 allele in predicting CD. Conclusions: There is a synergistic effect of perceived problems meeting BN and the APOE ε4 allele on jointly influencing cognitive functioning. Although genetic risk factors are not easily modifiable, resource deprivation may be more amenable to interventions, which may reduce risk for CD.

Depressed older patients with the atypical features of interpersonal rejection sensitivity and reversed-vegetative symptoms are similar to younger atypical patients

OBJECTIVES The atypical depression (AD) subtype has rarely been examined in older patients. However, younger AD patients have been characterized as having more severe and chronic symptoms of depression compared with non-AD patients. DESIGN Secondary data analysis by using analyses of variance and Growth Curve Modeling. SETTING Clinical Research Center for the study of depression in later life. PARTICIPANTS Depressed older patients (N = 248) followed over 2 years. METHOD In a longitudinal study, we examined depression severity and chronicity in patients with major depression with some features of AD, specifically rejection sensitivity and reversed-vegetative symptoms (e.g., hyperphagia and hypersomnia), or leaden paralysis, and compared them to non-AD patients. The Diagnostic Interview Schedule (DIS) was used to assess depressive symptoms and history. Depression severity and chronicity were assessed every 3 months by using the Montgomery Asberg Depression Rating Scale. RESULTS The AD symptom group reported more DIS depressive symptoms, more thoughts about wanting to die, earlier age of onset, poorer social support, and double the number of lifetime episodes than non-AD patients. Growth curve analyses revealed that, compared with non-AD patients, the AD symptom group had more residual symptoms of depression during the first year of follow-up but not during the second year. CONCLUSION Characteristics of older patients with features of AD are similar to younger patients. Assessment of atypical symptoms, in particular, rejection sensitivity and reversed-vegetative symptoms, is essential and should be considered in treatment plans.