Biomedical subjects

David C Steffens

Publications and source records attributed to David C Steffens.

81 records · Page 5Linked to original sources

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Statin use and hippocampal volumes in elderly subjects at risk for Alzheimer's disease: a pilot observational study.

Statins are investigational therapies for preventing or treating Alzheimer's disease (AD) and mild cognitive impairment (MCI). Hippocampal atrophy is a characteristic feature of MCI and AD. This study analyzed cross-sectional data from 246 nondemented elderly subjects to test the effect of lipid lowering agent (LLA) therapy on cognition and brain magnetic resonance imaging (MRI) measures of white matter lesions and hippocampal volume. The study also compared rates of hippocampal volume change over two and four years in a smaller subset. At baseline, LLA users were younger, better educated, more likely to be male, and had higher cognitive scores. Cognitive performance also varied by age and gender, and MRI measures varied by age. After adjusting for these differences, the effect of LLA use on baseline cognition, baseline hippocampal volume, and baseline white matter lesion scores was not significant. The effect of LLA use on hippocampal volume loss at two-year and four-year follow-ups was also not significant. This study is the first to examine statin effects on brain atrophy measured by MRI. In this cohort, statin use was not associated with rate of change of hippocampal volume. While the study was limited by a relatively small number of statin users, the findings seem consistent with three prior randomized trials that found no cognitive benefits for statins in nondemented subjects. Prospective studies in both nondemented and AD subjects may provide more conclusive answers.

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Prevalence and clinical correlates of neuropsychiatric symptoms in dementia.

The purpose of this research was to assess the frequency and severity of neuropsychiatric and behavioral symptoms and to examine the association between preexisting medical conditions and specific neuropsychiatric symptoms in demented individuals. We studied 211 demented subjects (87.7 percent male) who were participants in epidemiological studies of dementia. Using the Neuropsychiatric Inventory (NPI), we assessed the frequency and severity of neuropsychiatric symptoms. We collected medical history information during a structured telephone interview. Our analyses focused on determining prevalence of neuropsychiatric symptoms by dementia diagnosis and severity. We also examined the association of history of head injury, alcohol abuse, and stroke with development of neuropsychiatric symptoms. We found that neuropsychiatric symptoms were common, with approximately three-fourths of the subjects exhibiting at least one symptom during the preceding month. Apathy (39.3 percent), agitation (31.8 percent), and aberrant motor behavior (31.1 percent) were the most frequent symptoms. Frequency and severity of symptoms were similar for the all-dementia and Alzheimer's disease-only groups, neuropsychiatric symptoms varied by severity of dementia, but generally not in a consistent ordinal pattern. History of alcohol abuse, head injury, or stroke was associated with presence of specific neuropsychiatric symptoms in dementia. While psychiatric symptoms are common in dementia, they also vary by type and severity of dementia. The finding that certain medical conditions may increase risk for specific types of neuropsychiatric symptoms expands our knowledge of the natural history of dementia and should improve management of dementia in medically ill patients. Our results may also shed light on mechanisms that underlie neuropsychiatric symptoms.

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Hippocampal volume and incident dementia in geriatric depression.

The authors investigated the role of baseline hippocampal volume on later clinical emergence of dementia in a group of older, non-demented depressed individuals. Subjects were 115 depressed, non-demented participants in a mental health clinical research center. All subjects were screened for dementia and agreed to have a magnetic resonance imaging (MRI) brain scan at baseline. Subjects were clinically evaluated by geriatric psychiatrists quarterly for up to 5 years and received annual neuropsychological testing. Bivariate analyses examined age, gender, race, educational level, baseline depression severity, age at depression onset, baseline Mini-Mental State Exam (MMSE), left and right hippocampal volume, and total cerebral volume. Age, baseline MMSE, total cerebral volume, and having a small left hippocampal volume were associated with later dementia and were included in subsequent survival analysis. Small left hippocampal volume was significantly associated with later dementia (hazard ratio=2.762). Small left hippocampal size on neuroimaging may be a marker for dementia in depressed patients who have not yet met criteria for a clinical diagnosis of a dementing disorder.

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Provisional diagnostic criteria for depression of Alzheimer disease.

The authors, a group of investigators with extensive research and clinical experience related to both late-life depression and Alzheimer disease (AD), propose provisional affective and behavioral inclusion and exclusion diagnostic criteria for Depression of AD.

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Allelic differences in the serotonin transporter-linked polymorphic region in geriatric depression.

Previous studies have examined the role of genetic variations in the serotonin transporter-linked polymorphic region (5HTTLPR) in affective disorders. The authors studied 182 older depressed subjects and 107 elderly control subjects and obtained DNA for genotyping at the 5HTTLPR. There were no significant differences in allele frequencies generally or for number of short alleles for the group as a whole, but interesting gender effects emerged. Among men, 23% of depressed men had two short alleles, compared with only 5% of control subjects. Among women, 67% of depressed women with more than one episode had at least one short allele, compared with 41% of single-episode female patients. Also, 74% of women with a positive family history of psychiatric illness in any female relative had at least one short allele, whereas 53% had at least one short allele who did not have such a family history. Our results add to the literature linking this gene to affective illness. The negative association of allele frequency and depression may be related to the relatively small sample size. The findings raise the possibility that this genetic locus may exert differential effects based on gender, increasing risk in men, and increasing risk of recurrence in women.

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Sociodemographic and clinical predictors of mortality in geriatric depression.

OBJECTIVE: It is well documented that depression and early mortality are related, and current research suggests that depression may influence vascular causes of death. The authors report on prospectively observed mortality in elderly depressed patients, comparing differences in sex and vascular risk. METHODS: The subjects were 338 patients with unipolar major depression; patients with neurological or other psychiatric disorders were excluded. All subjects received a clinical evaluation and a standardized interview to establish DSM-III depression diagnosis. The cohort had a mean age of 67.2 years and was followed up at approximately 10 years from last contact. RESULTS: Mortality was associated with older age, older age at depression onset, and being male. Also, in men, mortality was associated with higher baseline CES-D scores, and, in women, with having a higher vascular risk rating or late age at depression onset. CONCLUSION: This is the first study demonstrating a gender-by-vascular condition interaction effect on mortality. Women with vascular risk factors may require closer follow-up to control vascular conditions. The relationship between greater depression and increased mortality risk among men is interesting, and further studies will be required to replicate and understand it.

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Time-to-remission from geriatric depression: psychosocial and clinical factors.

OBJECTIVE: The authors examined psychosocial and clinical predictors of time-to-remission in a sample of initially clinically depressed elderly patients. METHODS: Using a standardized algorithm, a prospective cohort study enrolled 239 patients undergoing treatment. Patients were followed for up to 4.5 years, until death or withdrawal from the study. Baseline predictor variables included psychosocial factors, such as four domains of social support; basic and instrumental activities of daily living; and clinical factors, including use of electroconvulsive therapy (ECT), past history of depression, comorbidities, and antidepressant treatment. RESULTS: Only 33% of the sample (n=79) met our classification for depression remission. A lack of instrumental and subjective social support, poor self-rated health, the use of antipsychotic medication, or use of an antidepressant in the last 7 days were predictors of longer time-to-remission. Use of ECT in the last year was related to shorter time-to-remission. CONCLUSION: Baseline psychosocial factors were just as important, as predictors of depression remission, as were clinical and diagnostic variables. Interventions directed toward social support resources, in addition to clinical intervention, including the use of ECT where appropriate, are likely to improve rates of depression remission.

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Greater depression severity associated with less improvement in depression-associated cognitive deficits in older subjects.

OBJECTIVES: Elderly depressed patients often exhibit cognitive deficits, which may improve with drug therapy. The authors investigated the relationship of baseline depression severity and cognitive improvement with antidepressant treatment in depressed patients with mild cognitive impairment. METHODS: Mini-Mental State Exam (MMSE) and Montgomery-Asberg Depression Rating Scale (MADRS) scores were measured in 52 depressed geriatric patients without dementia at baseline, 6, and 12 months, during an intent-to-treat period. A repeated-measures regression model tested the effect of MADRS score on MMSE. RESULTS: MMSE changes were significant and linear over time, with an average increase of 0.72 in the MMSE per 6-month interval. The final model showed that for every point increase in baseline MADRS, the average 6-month increase in MMSE decreased by 0.12. Repeated MADRS measurements did not significantly alter its predictive value. CONCLUSION: Greater baseline depression severity in older subjects with mild cognitive deficits is associated with less improvement in those deficits even with successful antidepressant therapy.

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Partial response as a predictor of outcome in geriatric depression.

OBJECTIVE: Although geriatric depression generally responds to treatment, patients are often left with residual symptoms after acute treatment. Data are lacking on the eventual outcomes of individuals who are partial responders or poor responders to initial treatment. METHODS: The authors examined 200 patients initially treated with a treatment-based guideline approach that allowed for physician choice. RESULTS: After 3 months, 34.0% of patients were remitted, 37.5% had achieved a partial response, and 28.5% were still highly symptomatic. After 6 months of treatment, 51.1% of patients were remitted, 36.5% were partial responders, and 12.5% were still experiencing significant depressive symptoms. Cumulative remission rates over 18 months of treatment were significantly higher among partial responders than among highly symptomatic patients at 6 months, but not at 3 months. In terms of relapse, defined as a Montgomery-Asberg Depression Rating Scale score greater than 15, 42.0% of the remitted and partial-responder groups had relapsed by 18 months. When compared with remitted patients, partial responders at 6 months were more likely to experience a relapse. There were no differences in relapse rate between the two groups at 3 months. CONCLUSION: These results suggest that during ongoing active treatment of geriatric depression, the level of improvement at 6 months, but not 3 months, is predictive of subsequent course.

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