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Biomedical subjects

D C Steffens

Publications and source records attributed to D C Steffens.

At least 19 recordsLinked to original sources
PubMed2001

Hormone replacement therapy and reduced cognitive decline in older women: the Cache County Study.

OBJECTIVE: To examine the association between postmenopausal hormone replacement therapy (HRT) and the trajectory of global cognitive change with age. METHODS: The Modified Mini-Mental State Examination (MMSE) was administered to a population sample of 2,073 nondemented, community-dwelling female residents of Cache County, UT, aged 65 and older. Current and past HRT and other medications at a baseline interview and at follow-up 3 years later were assessed. Between interviews, a telephone Women's Health Questionnaire was administered to assess initial exposure, duration, and recency of HRT. Generalized estimating equation marginal models were used to evaluate the cross-sectional and longitudinal relations of HRT and modified MMSE score. Also assessed were effects with multivitamins and calcium supplements as exposures likely to reflect a "healthy lifestyle" among HRT users. Model covariates included the presence of APOE epsilon4 alleles, age, education, concurrent depression, several chronic diseases, and self-perceived general health. RESULTS: Age, lower education, depression, and APOE epsilon4 were all associated with lower baseline modified MMSE scores. With these covariates in the model, lifetime HRT use was associated with better baseline modified MMSE scores and a slower rate of decline. Stratification by APOE genotype did not alter these effects. Apparent benefits with HRT were attenuated but remained significant after elimination of scores from participants with incident dementia. A significant interaction between age and HRT indicated the strongest effects in women aged 85 and older. Measures of age at initial use of HRT, duration, and recency of exposure did not improve the models. No effects were seen with the "healthy lifestyle" control exposures. CONCLUSIONS: In a population cohort of older women, lifetime HRT exposure was associated with improved global cognition and attenuated decline over a 3-year interval. Improvements were greatest in the oldest old.

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PubMed2001

Performance feedback deficit in geriatric depression.

BACKGROUND: The orbital frontal cortex is involved with processing of performance feedback. This study tests the hypothesis that older depressed subjects, compared with elderly control subjects, commit more subsequent errors after receiving feedback from an initial error. METHODS: We administered 116 older depressed patients and 139 control subjects the Trail Making Test Part B (TRAILS-B). Subjects who committed an error on TRAILS-B were immediately given feedback on performance. We then measured the frequency of making an error on the subsequent three tries. The likelihood of making any subsequent error was examined. RESULTS: After controlling for the overall initial error rate, more depressed patients than control subjects made subsequent errors. This association remained significant in later regression models. When the depressed group was examined in additional models, severity of depression was not associated with increased subsequent errors. CONCLUSIONS: These results extend previous findings suggesting a performance feedback deficit in geriatric depression. The findings support previous studies linking the orbital frontal cortex and depression.

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PubMed2001

MRI correlates of suicide attempt history in unipolar depression.

BACKGROUND: Suicide represents a major health problem in the United States, and prediction of suicide attempts is difficult. No structural neuroimaging studies have been done to specifically examine findings in patients who have attempted suicide. The objective of this study was to compare MRI findings in unipolar patients with and without a history of a suicide attempt. METHODS: In this post hoc analysis, 20 unipolar subjects with a history of a suicide attempt were matched by age and gender to unipolar subjects without a history of an attempt. Subjects were also matched on parameters such as cardiovascular history, electroconvulsive treatment history, and history of psychosis. Subjects with a history of any neurologic condition were excluded. There were no significant differences in age of onset of depression, number of episodes of depression, and Hamilton Depression scores between the two groups. T2-weighted magnetic resonance imaging (MRI) scans were rated using the Coffey and Boyko rating scales. RESULTS: Unipolar patients with a history of a suicide attempt demonstrated significantly more subcortical gray matter hyperintensities compared with patients without such a history. CONCLUSIONS: Patients with abnormal MRI findings may be at higher risk for mood disorders and suicide attempts because of disruption of critical neuroanatomic pathways. Gray matter hyperintensities in the basal ganglia may be especially associated with risk for suicide attempts.

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PubMed2001

Evidence of white matter tract disruption in MRI hyperintensities.

BACKGROUND: Diffusion tensor imaging (DTI) of brain tissue measures the apparent diffusion coefficient (ADC), or isotropic diffusion, and anisotropy, or diffusion as influenced by tissue structure. We hypothesized that hyperintensities, when compared with normal tissue by DTI, would show evidence of damage through an increased ADC and decreased anisotropy. We also hypothesized that DTI changes in hyperintensities would be similar between depressed subjects and control subjects. METHODS: Fourteen depressed geriatric patients and nineteen control subjects received DTI. The ADC and aniso-tropy of normal tissue from standard regions were compared with hyperintensities from these regions. The Students' t test compared individual regions and averaged white matter results. RESULTS: Hyperintensities showed higher ADC and lower anisotropy than normal regions. Gray matter exhibited similar trends. There was no significant difference in diffusion characteristics of hyperintensities between subjects and control subjects. CONCLUSIONS: Hyperintensities damage the structure of brain tissue, and do so comparably in depressed subjects and control subjects.

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PubMed2001

Bupropion SR in the naturalistic treatment of elderly patients with major depression.

INTRODUCTION: Bupropion immediate release (IR) and bupropion sustained release (SR) are frequently used to treat geriatric depression, as they have few cardiovascular, gastrointestinal and sexual adverse effects. We sought to examine the efficacy and dosing patterns of bupropion in a naturalistic cohort of elderly subjects with major depression (MD). METHODS: 31 elderly ( > 60 years) patients with unipolar MD (DSM-IV) who were enrolled in Duke's Mental Health Clinical Research Center for the Study of Depression in Later Life were prescribed bupropion SR or IR, alone or in combination with other antidepressant agents, for 12 weeks. Montgomery-Asberg depression rating scale (MADRS) scores and clinical global impression (CGI) severity scores were used to define response. RESULTS: 74% (23/31) of the sample were responders (MADRS < 15) and 53% (16/30) achieved a partial (CGI = 2) or complete (CGI = 1) remission of MD at week 12. Among patients treated with bupropion SR monotherapy, the mean (range) maximal daily dose achieved was 240 mg (150-400 mg). Among those treated with bupropion IR, the mean (range) maximum daily dose achieved was 258 mg (150-450 mg). In subjects on monotherapy, 67% (10/15) of MD subjects were responders (MADRS < 15) and 50% (7/14) achieved full or partial remission. Response rates did not differ statistically among those with high and low medical comorbidity. CONCLUSIONS: In this naturalistic 12-week study, geriatric MD patients with high and low medical comorbidity responded well to bupropion and bupropion SR. In elderly patients, four to eight week acute treatment periods may be insufficient. Our findings suggest that nearly 50% of elderly depressed subjects at a tertiary center may need combination therapy over the course of their illness. Controlled randomized studies to establish the long-term efficacy and optimal dose of the newer antidepressants in geriatric depression are urgently needed.

Administration, Oral↗
PubMed2001

Neuropsychiatric disturbance in Alzheimer's disease clusters into three groups: the Cache County study.

OBJECTIVE: We investigated the frequency and inter-relationship of neuropsychiatric disturbances in a population sample of persons suffering from Alzheimer's disease (AD). METHOD: Screening 5,092 elderly residents (90% of the population aged 65 and older) of Cache County, Utah, for dementia, we identified 198 persons with AD using a comprehensive neuropsychiatric examination protocol. This examination included the Neuropsychiatric Inventory (NPI), a widely used measure of dementia-associated neuropsychiatric disturbances. RESULTS: Overall, 60% of individuals with AD reported one or more neuropsychiatric symptoms. A latent class analysis revealed that these participants could be classified into three groups (classes) based on their neuropsychiatric symptom profile. The largest class included cases with no neuropsychiatric symptoms (40%) or with a mono-symptomatic disturbance (19%). A second class (28%) exhibited a predominantly affective syndrome, while a third class (13%) had a psychotic syndrome. CONCLUSION: Data from this first US population-based study of AD-associated neuropsychiatric disturbances suggest that a significant majority of persons with AD suffer from one or more neuropsychiatric disturbance. Based on phenomenological study, the spectrum of neuropsychiatric symptoms in AD can be empirically classified into three groups: an affective syndrome, a psychotic syndrome and other neuropsychiatric disturbance. The biologic and predictive validity of this classification merits further investigation.

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PubMed2001

Severity of subcortical gray matter hyperintensity predicts ECT response in geriatric depression.

OBJECTIVE: To determine the effect of subcortical white and gray matter lesions on ECT outcome. METHOD: 41 geriatric psychiatric inpatients underwent an MRI scan during their ECT work-up. Periventricular, deep white matter, and subcortical gray matter hyperintensities were graded. The associations of low versus high hyperintensity ratings and symptom scores, Clinical Global Impression severity (CGS) ratings, Montgomery-Asberg Depression Scale score, and number of treatments were examined using t-tests and repeated measures ANOVA. RESULTS: Patients with more severe subcortical gray hyperintensities (SCG) had significantly less improvement as measured by CGS ratings. CONCLUSIONS: SCG severity may limit the improvement of patients receiving ECT. Further studies are needed to examine differences based on electrode placement and to determine whether patients with severe SCG may require more ECT treatments in an index course.

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PubMed2001

Does social support buffer functional decline in elderly patients with unipolar depression?

OBJECTIVE: This study tested whether social support protects against functional decline, either generally or selectively, in the most severely depressed elderly patients undergoing treatment for major depressive disorder. METHOD: In a prospective cohort study design, 113 patients with incident and prevalent unipolar depression were followed for 12 months while they were undergoing naturalistic treatment. Outcome measures included performance on basic and instrumental activities of daily living; predictor variables included Hamilton Depression Rating Scale scores and four domains of informal social support. The analysis employed multivariable ordinary least squares regression models. RESULTS: Improved scores on instrumental activities of daily living and stable scores on basic activities of daily living characterized the subjects. In adjusted analyses, instrumental social support provided marginal protection against worsening performance on instrumental activities of daily living, which were primarily a function of baseline depression severity. Large social networks, more frequent social interaction, and the perceived adequacy of social support played a modest buffering role against declines in performance on basic activities of daily living among the most depressed elderly patients. CONCLUSIONS: Instrumental support was generally protective against worsening performance on instrumental abilities of daily living among elderly patients with recurrent unipolar depression. Subjective and structural dimensions of social support protected the most severely depressed elderly patients against the loss of basic maintenance abilities.

Activities of Daily Living↗
PubMed2000

Reduction of orbital frontal cortex volume in geriatric depression.

BACKGROUND: Postmortem studies have documented abnormalities in the medial orbital frontal cortex in depressed patients. In this study we evaluated whether atrophy of this region can be identified in older depressed patients using magnetic resonance imaging. METHODS: Twenty elderly patients meeting DSM-IV criteria for major depression and 20 matched control subjects were studied. The orbital frontal cortex was measured in both hemispheres using magnetic resonance imaging. RESULTS: Depressive patients had reduced volume in the total orbital frontal cortex, right orbital frontal cortex, and left orbital frontal cortex. CONCLUSIONS: Our finding of a reduction in orbital frontal cortex volume in both sides of the brain suggests that this region of the brain may have a critical role in the development of depression and raises questions about the etiology of the changes.

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PubMed2000

Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias.

BACKGROUND: The association between antecedent head injury and AD is inconsistent. OBJECTIVE: To examine the association between early adult head injury, as documented by military hospital records, and dementia in late life; and to evaluate the interaction between head injury and APOE epsilon4 as risk factors for dementia. METHODS: The study had a population-based prospective historical cohort design. It included men who were World War II Navy and Marine veterans, and were hospitalized during their military service with a diagnosis of either a nonpenetrating head injury or another unrelated condition. In 1996 to 1997, military medical records were abstracted to document the occurrence and details of closed head injury. The entire sample was then evaluated for dementia and AD using a multistage procedure. There were 548 veterans with head injury and 1228 without head injury who completed all assigned stages of the study. The authors estimated risk of dementia, specifically AD, using proportional hazards models. RESULTS: Both moderate head injury (hazard ratio [HR] = 2.32; CI = 1.04 to 5.17) and severe head injury (HR = 4.51; CI = 1.77 to 11.47) were associated with increased risk of AD. Results were similar for dementia in general. The results for mild head injury were inconclusive. When the authors stratified by the number of APOE epsilon4 alleles, they observed a nonsignificant trend toward a stronger association between AD and head injury in men with more epsilon4 alleles. CONCLUSIONS: Moderate and severe head injuries in young men may be associated with increased risk of AD and other dementias in late life. However, the authors cannot exclude the possibility that other unmeasured factors may be influencing this association.

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PubMed2000

Hippocampal volume in geriatric depression.

BACKGROUND: There is a growing literature on the importance of hippocampal volume in geriatric depression. METHODS: We examined hippocampal volume in a group of elderly depressed patients and a group of elderly control subjects (N = 66 geriatric depressed patients and 18 elderly nondepressed control subjects) recruited through Duke's Mental Health Clinical Research Center for the Study of Depression in the Elderly. The subjects received a standardized evaluation, including a magnetic resonance imaging scan of the brain. Patients had unipolar major depression and were free of comorbid major psychiatric illness and neurologic illness. Differences were assessed using t tests and linear regression modeling. RESULTS: Accounting for the effects of age, gender, and total brain volume, depressed patients tended to have smaller right hippocampal volume (p =.014) and left hippocampal volume (p =.073). Among depressed patients, age of onset was negatively but not significantly related to right hippocampal volume (p =.052) and to left hippocampal volume (p =.062). We noted that among subjects with either right or left hippocampal volume of 3 mL or less, the vast majority were patients rather than control subjects. CONCLUSIONS: These results support a role for hippocampal dysfunction in depression, particularly in late-age onset depression. Longitudinal studies examining both depressive and cognitive outcomes are needed to clarify the relationships between the hippocampus, depression, and dementia.

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PubMed2000

APOE and AD concordance in twin pairs as predictors of AD in first-degree relatives.

OBJECTIVE: To examine the independent effects of the APOE genotype (APOE) and concordance for AD in twin pairs on the occurrence of AD in first-degree relatives. BACKGROUND: Studies of twins have been undertaken to investigate the influence of genes in a variety of conditions, including AD. A previous study, performed before reports linking APOE to AD, demonstrated an increase in AD among first-degree relatives of twins concordant for AD compared with relatives of discordant twins. METHODS: In a sample of 94 twin pairs the authors examined the association between concordance for AD within the twin pair and family history of AD among first-degree relatives of twins. They then examined the extent to which the presence of the APOE epsilon4 allele in the twin pair explains the association between concordance for AD within the twin pair and family history of AD. RESULTS: Concordance among twins was associated with increased risk of AD among relatives (logrank test, chi2 = 12.558; p = 0.0004), and the presence of at least one APOE epsilon4 allele in each member of the twin pair is also associated with increased risk of AD among family members (logrank test, chi2 = 7.712; p = 0.0055). CONCLUSIONS: APOE genotype explains much but not all of the association between concordance among twins and increased familial risk of AD.

Age of Onset↗
PubMed2000

Prevalence of depression and its treatment in an elderly population: the Cache County study.

BACKGROUND: Previous estimates of the prevalence of geriatric depression have varied. There are few large population-based studies; most of these focused on individuals younger than 80 years. No US studies have been published since the advent of the newer antidepressant agents. METHODS: In 1995 through 1996, as part of a large population study, we examined the current and lifetime prevalence of depressive disorders in 4,559 nondemented individuals aged 65 to 100 years. This sample represented 90% of the elderly population of Cache County, Utah. Using a modified version of the Diagnostic Interview Schedule, we ascertained past and present DSM-IV major depression, dysthymia, and subclinical depressive disorders. Medication use was determined through a structured interview and a "medicine chest inventory." RESULTS: Point prevalence of major depression was estimated at 4.4% in women and 2.7% in men (P= .003). Other depressive syndromes were surprisingly uncommon (combined point prevalence, 1.6%). Among subjects with current major depression, 35.7% were taking an antidepressant (mostly selective serotonin reuptake inhibitors) and 27.4% a sedative/hypnotic. The current prevalence of major depression did not change appreciably with age. Estimated lifetime prevalence of major depression was 20.4% in women and 9.6% in men (P<.001), decreasing with age. CONCLUSIONS: These estimates for prevalence of major depression are higher than those reported previously in North American studies. Treatment with antidepressants was more common than reported previously, but was still lacking in most individuals with major depression. The prevalence of subsyndromal depressive symptoms was low, possibly because of unusual characteristics of the population.

Age Factors↗
PubMed2000

Relation of subjective and received social support to clinical and self-report assessments of depressive symptoms in an elderly population.

BACKGROUND: The authors sought to evaluate the associations between depressive symptoms and social support in a sample drawn from a relatively understudied population - depressed elderly patients. The present study also used a multi-measure approach to assess both depressive symptomatology and social support. METHODS: In this prospective study of 115 patients we examined: (1) the baseline relations among a self-report measure of depressive symptoms, two clinical assessments of depressive symptoms, and subjective and received social support, and (2) the ability of social support to predict changes in clinical assessments of depressive symptoms at 6 months and 1 year. Education level, financial concerns, activities of daily living ratings, and gender were controlled for. RESULTS: Baseline subjective support was negatively related to self-reports of depressive symptoms, but unrelated to clinical assessments at baseline or follow-up. Conversely, received support was unrelated to self-reported depressive symptoms, but positively related to both clinical assessments at baseline. However, higher ratings of received support at baseline predicted decreases in clinical ratings of depressive symptoms at 6 months and 1 year. LIMITATIONS: These data were gathered in a primarily Caucasian sample, thus the findings may not generalize to more diverse ethnic populations. Potential confounding due to treatment mode and setting was not controlled in the present analyses. CONCLUSIONS: These results have important implications for interpreting clinical data in elderly depressed patients. Specifically, when depressive symptoms are assessed using clinician ratings, the most informative aspect of social support with respect to future clinical status appears to be received, rather than perceived, support measures.

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PubMed2000

Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging.

OBJECTIVE: The authors report findings from a study of 5,092 community residents who constituted 90% of the elderly resident population of Cache County, Utah. METHOD: The 5,092 participants, who were 65 years old or older, were screened for dementia. Based on the results of this screen, 1,002 participants (329 with dementia and 673 without dementia) underwent comprehensive neuropsychiatric examinations and were rated on the Neuropsychiatric Inventory, a widely used method for ascertainment and classification of dementia-associated mental and behavioral disturbances. RESULTS: Of the 329 participants with dementia, 214 (65%) had Alzheimer's disease, 62 (19%) had vascular dementia, and 53 (16%) had another DSM-IV dementia diagnosis; 201 (61%) had exhibited one or more mental or behavioral disturbances in the past month. Apathy (27%), depression (24%), and agitation/aggression (24%) were the most common in participants with dementia. These disturbances were almost four times more common in participants with dementia than in those without. Only modest differences were observed in the prevalence of mental or behavioral disturbances in different types of dementia or at different stages of illness: participants with Alzheimer's disease were more likely to have delusions and less likely to have depression. Agitation/aggression and aberrant motor behavior were more common in participants with advanced dementia. CONCLUSIONS: On the basis of their findings in this large community population of elderly people, the authors conclude that a wide range of dementia-associated mental and behavioral disturbances afflict the majority of individuals with dementia. Because of their frequency and their adverse effects on patients and their caregivers, these disturbances should be ascertained and treated in all cases of dementia.

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PubMed1999

Initial evaluation of suspected dementia. Asking the right questions.

The initial clinical approach to suspected dementia involves asking the right questions of the patient and a knowledgeable family member or caregiver. These questions should focus on the nature of the cognitive problem (e.g., the onset, duration, and severity of memory difficulties). The clinical interview is supplemented with thorough examination of the patient's physical, neurologic, mental, and functional status. Once a diagnosis of dementia is established, the underlying cause should be identified by a standardized workup, including laboratory testing and, in most cases, neuroimaging. Genetic testing for the APOE epsilon 4 allele can help confirm the diagnosis in patients with late-onset familial or sporadic Alzheimer's disease.

Dementia↗
PubMed1999

APOE-epsilon4 count predicts age when prevalence of AD increases, then declines: the Cache County Study.

OBJECTIVE: To examine the prevalence of Alzheimer's disease (AD) and other dementias in relation to age, education, sex, and genotype at APOE. Recent studies suggest age heterogeneity in the risk of AD associated with the APOE genotype and a possible interaction between APOE-epsilon4 and female sex as risk factors. We studied these topics in the 5,677 elderly residents of Cache County, Utah, a population known for long life expectancy and high participation rates. METHODS: We screened for dementia with a brief cognitive test and structured telephone Dementia Questionnaire, then examined all individuals with apparent cognitive symptoms and a sample of others. We estimated age-specific prevalence of AD and other dementias and used multiple logistic regression models to describe relation of AD prevalence to age, sex, education, and APOE genotype. RESULTS: We found 335 demented individuals, 230 (69%) with definite, probable, or possible AD (positive predictive value versus autopsy confirmation 85%). The adjusted prevalence estimate for AD was 6.5% and for all dementias 9.6%. After age 90, the adjusted prevalence estimate for AD was 28% and for all dementias 38%. Regression models showed strong variation in AD prevalence with age, sex, education, and number of epsilon4 alleles (effect of epsilon2 not significant). Models were improved by a term for age-squared (negative coefficient) and by separate terms for interaction of age with presence of one or two epsilon4 alleles. An association of AD with female sex was ascribable entirely to individuals with epsilon4. CONCLUSIONS: In participants with no epsilon4 alleles, the age-specific prevalence of AD reached a maximum and then declined after age 95. In epsilon4 heterozygotes a similar maximum was noted earlier at age 87, in homozygotes at age 73. Female sex was a risk factor for AD only in those with epsilon4. The epsilon4 allele accounted for 70% of the population attributable risk for AD.

Age Distribution↗