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Biomedical subjects

D C Steffens

Publications and source records attributed to D C Steffens.

At least 37 records · Page 2Linked to original sources
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.

Aged↗
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↗
PubMed1999

The effect of major depression on functional status in patients with coronary artery disease.

OBJECTIVE: To examine the effect of major depression on reported functional status in a group of patients with coronary artery disease (CAD). SETTING: An inpatient cardiology service. PARTICIPANTS: Three hundred thirty-five inpatients with coronary artery disease who were free of dementia, Parkinson's disease, and other primary neurological illnesses. MEASUREMENTS: Duke Depression Evaluation Schedule, a structured psychiatric interview which included the Diagnostic Interview Schedule depression subscale, the Cumulative Illness Rating Scale, and two scales for measuring instrumental and self-maintenance activities of daily living. RESULTS: Twenty-seven subjects met DSM-IV criteria for major depression. Compared with subjects without major depression, depressed subjects were more than twice as likely to report a self-maintenance ADL deficit and were significantly more likely to report an IADL deficit than were nondepressed subjects (93 vs 71%). In regression models, female gender, older age, greater medical illness severity, and presence of major depression were significant predictors of self-maintenance ADL disability; and female gender, older age, greater medical severity, and presence of major depression significantly predicted greater IADL impairment. CONCLUSION: The presence of major depression was associated with functional disability in patients with CAD. Further research is needed to clarify whether antidepressant treatment significantly impacts both affective symptoms and functional status in patients with coronary heart disease.

Activities of Daily Living↗
PubMed1999

Enhanced cognitive performance with estrogen use in nondemented community-dwelling older women.

OBJECTIVE: To examine the association between history of postmenopausal estrogen use and cognitive function in a large sample of nondemented community-dwelling older women. SETTING: A community of older residents in Cache County, Utah. PARTICIPANTS: A total of 2338 nondemented women aged 65 and older. MEASUREMENTS: All subjects were administered the Modified Mini-Mental State Examination (3MSE). Self-reported information on current and past use of estrogen after menopause was also obtained using a structured interview. Estrogen use was trichotomized as: no use, past use, and current use. Apolipoprotein E (APOE) genotype was determined and was dichotomized by the presence of an epsilon4 allele. A series of variance/covariance models was conducted with the 3MSE score as the dependent variable, first considering estrogen use alone, then adding, sequentially as covariates, education, age, health status, APOE genotype, current depression status, and history of head injury. RESULTS: In the simplest bivariate model, the 3MSE means (and confidence intervals) were 92.1 (91.7-92.4), 93.5 (93.1-93.9), and 94.4 (94.0-94.7) for never-, past-, and current users, respectively. In the final model (R2 = 0.28), no use of estrogen replacement therapy (P = .006), lower education (P < .001), poorer perceived health status (P = .035), current depression (P = .014), and presence of at least one APOE epsilon4 allele (P < .001) each independently predicted lower 3MSE score. Both current and past estrogen users had significantly higher 3MSE scores than never-users (P = .0063 and P = .0096, respectively). CONCLUSIONS: In this large community study, women who had used estrogen after menopause scored higher on the 3MSE. This finding remained, even after controlling for the effects of age, education, APOE genotype, and other variables that may affect cognition. These data support studies reporting a beneficial role of estrogen on cognition in postmenopausal women, particularly among current estrogen users.

Aged↗
PubMed1999

Cerebrovascular disease and depression symptoms in the cardiovascular health study.

BACKGROUND AND PURPOSE: Evidence is mounting linking cerebrovascular disease with depressive symptoms in the elderly. Lesions in both white and gray matter have been associated with depressive symptoms and major depression. We sought to investigate the relationship between depressive symptoms and white and gray matter lesions in subjects participating in the Cardiovascular Health Study. METHODS: In a sample of 3660 men and women who underwent a standardized interview, physical examination, and MRI scan, we examined the association between number of white and gray matter lesions and white matter grade (a measure of severity) and reported depressive symptoms using a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale. We controlled for a variety of demographic and medical variables as well as functional status and Modified Mini-Mental State Examination score. RESULTS: The number of small (<3 mm) basal ganglia lesions was significantly associated with reported depressive symptoms, but white matter grade was not. In subsequent logistic regression models, number of basal ganglia lesions remained a significant predictor after controlling for non-MRI variables and severity of white matter lesions. CONCLUSIONS: Our findings extend previous reports that linked cerebrovascular changes to depressive symptoms in clinical populations to a large community-based population. This report provides further evidence of the importance of basal ganglia lesions in geriatric depression.

Activities of Daily Living↗
PubMed1999

Disability in geriatric depression.

The authors examined impairment in self-maintenance skills and in instrumental activities of daily living (IADL) among 211 older patients with unipolar major depression. In regression models, self-maintenance impairment was associated with older age, less reported depressed mood, psychomotor retardation, and severe chronic medical illness. IADL deficit was associated with older age, greater severity of depression, less guilt, more apathy, weight loss, greater cognitive impairment, more severe chronic medical illness, less social interaction, lower subjective social support, and greater instrumental support. The authors conclude that efforts to remediate basic skills deficits in depressed older adults should focus on treating comorbid medical conditions; impaired IADL skills in geriatric depressed patients should improve with treatment of depression and medical illness. Clinicians should be aware that substantial IADL impairment may accompany mild cognitive impairment associated with depression in older patients.

Activities of Daily Living↗
PubMed1998

Magnetic resonance imaging signal hypointensity and iron content of putamen nuclei in elderly depressed patients.

We previously introduced a semiquantitative scale for assessment of iron content of putamen nuclei as determined by magnetic resonance imaging (MRI)--the Signal Hypointensity in the Putamen (SHIP) scale. Such hypointensity may be related to putamen nuclei iron content, although this suggestion remains controversial, especially in the elderly. In the present study, we apply the SHIP scale to a sample of 68 elderly depressed patients (diagnosed with DSM-IV major depression using the Diagnostic Interview Schedule and clinical interview) and a group of 28 age-matched non-depressed control subjects. MRI scans were conducted on a single 1.5-T General Electric Signa system with axial acquisitions obtained parallel to the canthomeatal line. Technical parameters were as follows: (1) repetition time (TR) = 500 ms and echo time (TE) = 15 ms for T1-weighted images; (2) TR = 2500 ms and TE = 30 ms for proton-density-weighted images; and (3) TR = 2500 ms and TE = 80 ms for T2-weighted images. Among depressed patients, older age of depression onset and greater severity of depression were associated with increased putamen nuclei iron deposition. When depressed patients were compared with control subjects, the patient group demonstrated greater putamen nuclei iron, but the finding was significant only for the left hemisphere. Our findings support previous neuroimaging studies linking both changes in the basal ganglia and greater left-sided brain pathology to late-life depression.

Age of Onset↗
PubMed1998

Structural neuroimaging and mood disorders: recent findings, implications for classification, and future directions.

Neuroimaging is playing an increasing role in research of affective disorders, with investigators examining both volumetric changes of specific brain structures and vascular changes within white and gray matter. Recent studies have attempted to make clinical correlations between neuroimaging changes in unipolar and bipolar mood disorders. In this review, we focus particularly on those changes that are clinically meaningful. We conclude that there is enough evidence to begin to evaluate inclusion of neuroimaging findings in our mood disorder classification system. To this end, we propose two new mood disorder subtypes, vascular depression and vascular mania. Directions for future research in neuroimaging are then discussed.

Bipolar Disorder↗
PubMed1998

Combination therapy for early Alzheimer's disease: what are we waiting for?

The practical pharmacological approaches currently available to palliate the cognitive and functional losses in early Alzheimer's disease (AD) include cholinesterase inhibitors (ChEI), antioxidants (e.g., vitamin E), anti-inflammatory agents, estrogen, seligiline, vasoactive agents, and ginkgo biloba. Reviewing available data on these therapies and using models from medical illnesses such as cancer and hypertension, we highlight the urgent need for evaluating combination therapies in early AD.

Aged↗
PubMed1998

Familial leukoencephalopathy in bipolar disorder.

OBJECTIVE: Imaging studies of patients with bipolar disorder demonstrate changes in deep white matter and subcortical gray nuclei that are seen as focal hyperintensities on T2-weighted magnetic resonance imaging (MRI). The objective of this study was to examine MRIs in a family with a strong history of bipolar disorder to look for possible MRI abnormalities in members with and without affective illness. METHOD: The authors obtained MRIs of 21 members of a family with a strong history of bipolar disorder. Eight of the family members studied had bipolar illness, one had symptoms of bipolar disorder but did not meet full DSM-III-R criteria, two had unipolar disorder, and 10 did not have bipolar disorder. RESULTS: Fifteen of the 21 family members had MRI findings, including six of 10 family members who had no affective disorder and all of those with bipolar disorder. Lesions of both white matter and subcortical gray nuclei were found. CONCLUSIONS: Although the clinical significance of these MRI findings is unknown, the high prevalence of MRI findings in both affected and unaffected family members suggests that MRI findings may potentially serve as a biological marker for bipolar disorder. Recent genetic studies have established a link between familial leukoencephalopathy and chromosome 19. If leukoencephalopathy appears to be related to bipolar disorder, it may allow clearer characterization of the genetics of the disorder.

Adolescent↗
PubMed1998

Psychotherapeutic agents in older adults. Metabolism, bioavailability, and drug interactions.

This article presents clinically relevant drug interactions which may confront the geriatric psychiatrist. Changes in drug metabolism due to aging, higher medical comorbidity, and frequent polypharmacy all place the older patient at a greater risk of developing a drug-drug interaction. Clinicians must be aware of the potential for such interactions, but they should also be able to determine which of those possible interactions is appropriate for a particular patient. Drug interactions are included in this article based on frequency of the interaction, clinical severity, and frequency of contact with the drugs prescribed by the practicing clinician.

Age Factors↗
PubMed1998

The use of flumazenil in the anxious and benzodiazepine-dependent ECT patient.

Many patients who receive electroconvulsive therapy (ECT) are benzodiazepine dependent or are anxious and require benzodiazepine drugs. Because these agents may diminish the therapeutic effectiveness of ECT, we explored the dosing, safety, and efficacy of pre-ECT flumazenil administration, a benzodiazepine-competitive antagonist, in patients receiving benzodiazepine medications. We report our experience with 35 patients who received both flumazenil and benzodiazepine drugs during their ECT course. We compared seizure duration with and without flumazenil and compared treatment efficacy to 49 patients who received ECT without either of these medications. Flumazenil could be safely administered with ECT. A few subjects taking higher chronic benzodiazepine dosages experienced breakthrough anxiety or withdrawal symptoms, which were well managed by dosing flumazenil immediately before the anesthetic agent and by immediate posttreatment benzodiazepine administration. A dose of 0.4-0.5 mg was adequate for all but those taking the highest benzodiazepine dosages, where 0.8-1.0 mg resulted in a clinically more effective reversal. No differences in efficacy or seizure duration were found as a function of flumazenil administration. Flumazenil offers the promise of safe and effective ECT in patients receiving benzodiazepine drugs. Follow-up outcome investigation on a random assignment basis will be necessary for definitive assessment of the value of flumazenil. In addition, the direct effect of benzodiazepine drugs and the flumazenil/benzodiazepine combination on ECT seizures remains to be determined.

Adult↗
PubMed1998

Early recognition of Alzheimer's disease: what is consensual? What is controversial? What is practical?

Alzheimer's disease is often unrecognized or misdiagnosed in its early stages. Despite the lack of curative treatments, there are compelling reasons why early recognition of Alzheimer's disease may offer substantial benefits. Early evaluation and diagnosis may offer opportunities to enhance patient safety, allow families to plan for the future, provide family education and support, and initiate the best treatment before more substantial neuronal loss occurs. Barriers to early diagnosis include failure of family or physicians to recognize the existence or importance of cognitive/functional changes and/or misperceptions regarding diagnostic requirements and treatment capabilities. There is consensus that high diagnostic accuracy can be achieved clinically, even by nonspecialists, using established criteria and practice parameters. Population-based screening programs for the elderly, genetic testing, yield of routine neuroimaging studies, and the diagnostic value of certain molecular markers remain controversial. This review highlights practical issues related to the initial clinical evaluation and differential diagnosis of Alzheimer's disease.

Aged↗
PubMed1997

A twin study of late-onset depression and apolipoprotein E epsilon 4 as risk factors for Alzheimer's disease.

A prior history of depression and the epsilon 4 allele of apolipoprotein E (APOE) have each been associated with development of Alzheimer's disease (AD). In a sample of 142 elderly twins from a large study of dementia, we examined the relation of major depression, APOE genotype and AD using time-dependent proportional hazards models. Compared against the risk for AD with no history of depression and no epsilon 4 allele, the risk ratio for AD with two epsilon 4 alleles was 2.87 (C.I. = 1.56-5.28), with one epsilon 4 allele, 1.82 (C.I. = 1.09-3.04) and with late-onset depression and no epsilon 4 allele, 2.95 (C.I. = 1.55-5.62). There was no suggestion of an interaction between prior depression and APOE genotype in their effects on AD risk. Results were similar when the sample was stratified by twin pair, so that a single genetic marker is unlikely to explain the relation among depression, APOE, and dementia. Risk ratios declined substantially with increasing intervals between the onset of depression and AD. Thus, for many individuals, the association of depression and AD may reflect the occurrence of prodromal depressive symptoms rather than a true risk relationship.

Age of Onset↗
PubMed1997

Are SSRIs better than TCAs? Comparison of SSRIs and TCAs: a meta-analysis.

In this analysis we examined studies of tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) to compare efficacy and drop-out rates. Frequency of reported side effects was also studied. Using Medline, we located 36 clinical trials of TCAs and SSRIs in a double-blind comparison. We performed a meta-analysis on these studies and on a subgroup of 21 studies that had more uniformly defined outcome criteria. The main outcome measures were efficacy for treatment completers and for the intention-to-treat group; drop-out rates due to adverse reactions and lack of efficacy; and reported side effects. Overall, the response rate to treatment for patients who completed a trial was 63.2% for SSRIs and 68.2% for TCAs (P = 0.038). For the intention-to-treat groups, these rates dropped to 48.0 and 48.6% (P, NS), respectively. Significantly more TCA-treated than SSRI-treated subjects dropped out due to either lack of efficacy or adverse reactions (30.0 vs. 24.7%, P = 0.01). Patients taking SSRIs experienced significantly more gastrointestinal problems and sexual dysfunction, whereas treatment with TCAs produced significantly more complaints of sedation, dizziness, and anticholinergic symptoms.

Antidepressive Agents, Tricyclic↗
PubMed1997

A review of racial differences in geriatric depression: implications for care and clinical research.

How racial differences influence depressed elders' seeking and obtaining treatment for depression is poorly understood. Studies in other medical illnesses show older African Americans use fewer health-care services for heart disease, stroke, and renal dialysis. This article reviews the racial composition of Duke University's Clinical Research Center (CRC) for the Study of Depression in the Elderly. Possible explanations for low participation of African Americans in such programs also are discussed. During most of the first year of the CRC project, minority enrollment varied from 5% to 10%, at least one third the African-American population of the area. Active efforts to improve minority recruitment increased this percentage to 15% by the end of the project's second year. Likely explanations for low minority participation rates include 1) elders may recognize depressive symptoms, but do not seek or cannot obtain medical treatment, and 2) depressive symptoms may be attributed to a crisis of the spirit (so help is sought through prayer and the church), the "slowing down" process of aging, or part of life's burden to be endured. Future attempts at both treatment and clinical research recruitment efforts are needed to address these possibilities.

Black or African American↗