Biomedical subjects

David C Steffens

Publications and source records attributed to David C Steffens.

At least 19 recordsLinked to original sources

PubMed2007

A preliminary metabolomic analysis of older adults with and without depression.

BACKGROUND: Metabolomics, the global science of biochemistry, is an emerging field that enables detection and quantification of small molecules involved in metabolic and signaling pathways. Metabolic signatures for disease and its treatment could provide valuable biomarkers and insights about disease mechanisms. In this pilot study, we evaluate the potential of metabolomics in the study of older depressed patients. METHODS: We performed a metabolomic analysis of blood plasma from nine depressed, 11 remitted, and ten never-depressed older adults. Approximately 800 metabolites were analyzed, with comparisons made among the three groups. RESULTS: Metabolites that were altered in currently depressed patients when compared with controls included several fatty acids, glycerol and gamma-aminobutyric acid (GABA). Analyses comparing concentrations in remitted and currently depressed patients revealed a pattern of metabolite alterations similar to the control vs currently depressed analyses. One difference observed in the remitted patients relative to the depressed patients was elevation of the concentration of the ketone 3-hydroxybutanoic acid. CONCLUSION: These observations suggest that the depressed state may be associated with alterations in the metabolism of lipids and neurotransmitters, and that treatment with antidepressants adjusts some of the aberrant pathways in disease so that the patients in remission have a metabolic profile more similar to controls than to the depressed population. These results will need to be examined and validated in larger longitudinal cohorts.

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PubMed2007

Coenzyme Q10: a review of its promise as a neuroprotectant.

Coenzyme Q10 (CoQ10) is a powerful antioxidant that buffers the potential adverse consequences of free radicals produced during oxidative phosphorylation in the inner mitochondrial membrane. Oxidative stress, resulting in glutathione loss and oxidative DNA and protein damage, has been implicated in many neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. Experimental studies in animal models suggest that CoQ10 may protect against neuronal damage that is produced by ischemia, atherosclerosis and toxic injury. Though most have tended to be pilot studies, there are published preliminary clinical trials showing that CoQ10 may offer promise in many brain disorders. For example, a 16-month randomized, placebo-controlled pilot trial in 80 subjects with mild Parkinson's disease found significant benefits for oral CoQ10 1,200 mg/day to slow functional deterioration. However, to date, there are no published clinical trials of CoQ10 in Alzheimer's disease. Available data suggests that oral CoQ10 seems to be relatively safe and tolerated across the range of 300-2,400 mg/day. Randomized controlled trials are warranted to confirm CoQ10's safety and promise as a clinically effective neuroprotectant.

Alzheimer Disease↗

PubMed2006

Vascular risk factors and cognitive decline among elderly male twins.

BACKGROUND: Studies investigating the association between cardiovascular risk factors and cognitive decline report discrepant outcomes. The co-twin control method improves on traditional case-control approaches by controlling for within-twin pair similarities of genetic and early environmental influences. OBJECTIVE: To examine the association of diabetes, hypertension, hypercholesterolemia, and elevated body mass index (BMI) (>30 kg/m(2)), individually and combined, with cognitive decline over a 12-year period in members of the National Academy of Sciences-National Research Council Twin Registry of World War II male veterans. METHODS: Modified Telephone Interview for Cognitive Status (TICS-m) was administered four times at approximately 4-year intervals from 1990 to 2002 as part of an epidemiologic study of dementia. Self-report medical information was collected from 1996 to 2002. We examined the difference in cognitive decline within twin pairs discordant for the vascular risk factors while controlling for baseline TICS-m, education, smoking, and alcohol history. RESULTS: Among twin pairs discordant for diabetes (n = 177), the diabetic twins declined an average of almost 1 point more than their nondiabetic co-twins (p = 0.018) at the last screening time point. Further analyses showed that this was in large part due to greater decline among older men (age 76 to 84 years). Cognitive change was not significantly different between members of pairs discordant for hypertension (n = 326), hypercholesterolemia (n = 282), or elevated BMI (n = 166). CONCLUSION: Based on this study of twin pairs who share similar genetic and early environmental risks for cardiovascular risk factors, diabetes is associated with greater cognitive decline, particularly among the oldest individuals.

Age Factors↗

PubMed2006

Food group intake and brain lesions in late-life vascular depression.

BACKGROUND: Studies indicate that diet may be related to the occurrence of brain lesions. The cross-sectional association between food intake and brain lesion volumes in late-life depression was examined in a cohort of elderly individuals with current or prior depression. METHODS: Food intake was assessed in 54 elderly vascular depression subjects (vascular depression defined by presence of hyperintensities on brain MRI) using a Block 1998 food frequency questionnaire. Food and kilocalorie intake were determined. Brain lesion volumes were calculated from MRI. Subjects were aged 60 or over and were participants in a longitudinal study of major depression. All subjects received psychiatric assessment and treatment, and medical comorbidity assessments. RESULTS: High-fat dairy and whole grains were significantly positively correlated with brain lesion volume, while other food groups were not significantly associated with lesion volume. In multivariable analyses, controlling for age, sex, hypertension, diabetes and total kilocalories, the positive association with lesion volume remained significant for both high-fat dairy and whole grains. CONCLUSIONS: High fat dairy and whole grain consumption may be associated with brain lesions in elderly subjects with depression.

Age of Onset↗

PubMed2006

Aging, gender, and the elderly adult brain: an examination of analytical strategies.

We sought to examine the relations between age, gender and brain volumes in an elderly population; we also sought to examine ways of measuring these relations. Three sets of analyses were used: correlational analyses, in which correlations between independent variables and brain volumes were calculated without correction for intracranial volume (ICV); covariational analyses, in which ICV was used as a covariate in regression equations; and ratio analyses, in which the dependent variable was the ratio of brain volume to ICV. These analyses yielded similar results, except that (as expected) adjusting for ICV altered estimates of gender differences. Analyses of age showed decreases in left caudate, putamen, and right hippocampus and an increase in CSF, a result generally in accord with previous findings. However, we also found a significant decrease of white-matter volumes and no significant decrease in total gray-matter volumes. Correlational analyses showed that men did not always have larger volumes despite their larger head size; women generally had larger volumes after adjusting for ICV. We found no age-gender interactions.

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PubMed2006

Psychiatric disease in the twenty-first century: The case for subcortical ischemic depression.

The current approach to psychiatric diagnoses involves identifying symptom clusters that fit a specific syndrome. Although this approach has facilitated the field's development, advances in genetics and neuroimaging raise the question of how causality may fit into the diagnostic process. One approach would be a two-axial system, wherein clinical presentation is on one axis and putative risk factors are on the other. This approach applies to subcortical ischemic depression (SID), a diagnosis corresponding to the "vascular depression" hypothesis. Subcortical ischemic depression affects clinical presentation, long-term outcomes, and response to antidepressant therapy, arguing that it is a valid diagnostic entity worth further study.

Brain Ischemia↗

PubMed2006

The neurosteroid allopregnanolone is reduced in prefrontal cortex in Alzheimer's disease.

BACKGROUND: Few data are currently available investigating neurosteroids (NS) in Alzheimer's disease (AD). The NS allopregnanolone may be decreased in serum and plasma in patients with AD, but it is unclear if allopregnanolone is also reduced in brain. Because a number of NS exhibit neuroprotective effects and impact cognitive performance in rodent models, these molecules may be relevant to the pathophysiology of neurodegenerative disorders. We therefore investigated prefrontal cortex (PFC) NS levels in AD. METHODS: Neurosteroid levels (allopregnanolone, pregnenolone, dehydroepiandrosterone [DHEA]) were determined in postmortem PFC in 14 male subjects with AD and 15 cognitively intact male control subjects by gas chromatography/mass spectrometry preceded by high-performance liquid chromatography purification. RESULTS: Subjects with AD exhibit significant reductions in allopregnanolone compared with cognitively intact control subjects (median levels = 2.50 ng/g vs. 5.59 ng/g, respectively; p = .02). Allopregnanolone levels are inversely correlated with neuropathological disease stage (Braak), r = -.49, p = .007. Median DHEA levels are elevated in subjects with AD (p = .01). CONCLUSIONS: Subjects with AD demonstrate significant reductions in PFC allopregnanolone levels, a finding that may be relevant to neuropathological disease stage severity. Neurosteroids may have utility as candidate biomarkers in AD.

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PubMed2006

Differences in brain volumes among males and female hormone-therapy users and nonusers.

Numerous studies have shown gender differences in the brain volumes of elderly adults. Some evidence shows that higher estrogen levels may be neuroprotective, suggesting that hormone therapy (HT) may in part be responsible for these gender differences; however, few studies have examined the relation between HT and brain volumes. Brain volumes of caudate, putamen, hippocampus, gray matter, white matter, white-matter lesions, and cerebrospinal fluid were measured on magnetic resonance imaging scans. A comprehensive neuropsychological battery was administered. Women were separated into two groups based on HT use, and we used multiple regression analyses to compare these groups with one another and with men. Results of brain-volume measurements showed that HT users had significantly less gray matter and more cerebrospinal fluid than nonusers. Results of the neuropsychological testing showed that HT users performed better on the Shipley Vocabulary Test than males did.

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PubMed2006

Dorsolateral prefrontal cortex and anterior cingulate cortex white matter alterations in late-life depression.

BACKGROUND: The dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) are critical for mood regulation. Alterations in the white matter connections of these regions may impair their role in mood regulation and increase the risk of developing depression. This study used diffusion tensor imaging to examine for white matter microstructural abnormalities of these regions and of central white matter structures in late-life depression. METHODS: One hundred six elderly depressed subjects and eighty-four elderly nondepressed subjects underwent clinical assessment and diffusion tensor imaging. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in regions of interest placed in the white matter of the DLPFC, ACC, corpus callosum, and internal capsule. Differences between groups were assessed, controlling for age, sex, and total cerebral volume. RESULTS: After controlling for covariates, depressed subjects had significantly lower FA values in white matter of the right ACC, bilateral superior frontal gyri, and left middle frontal gyrus. There were no significant differences in ADC values. CONCLUSIONS: Lower FA, representing lower tissue organization, is observed in depressed elders in the DLPFC and right ACC. These findings support the hypothesis that altered connectivity between brain regions contributes to the risk of depression.

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PubMed2006

Persistent mild cognitive impairment in geriatric depression.

BACKGROUND: Cognitive impairment often occurs with geriatric depression and impairments may persist despite remission of depression. Although clinical definitions of mild cognitive impairment (MCI) have typically excluded depression, a neuropsychological model of MCI in depression has utility for identifying individuals whose cognitive impairments may persist or progress to dementia. METHODS: At baseline and 1-year follow-up, 67 geriatric patients with depression had a comprehensive clinical examination that included depression assessment and neuropsychological testing. We defined MCI by a neuropsychological algorithm and examined the odds of MCI classification at Year 1 for remitted depressed individuals with baseline MCI, and examined clinical, functional and genetic factors associated with MCI. RESULTS: Fifty-four percent of the sample had MCI at baseline. Odds of MCI classification at Year 1 were four times greater among patients with baseline MCI than those without. Instrumental activities of daily living were associated with MCI at Year 1, while age and APOE genotype was not. CONCLUSIONS: These results confirm previous observations that MCI is highly prevalent among older depressed adults and that cognitive impairment occurring during acute depression may persist after depression remits. Self-reported decline in functional activities may be a marker for persistent cognitive impairment, which suggests that assessments of both neuropsychological and functional status are important prognostic factors in the evaluation of geriatric depression.

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PubMed2006

White matter and subcortical gray matter lesion volume changes and late-life depression outcome: a 4-year magnetic resonance imaging study.

BACKGROUND: Cross-sectional studies have shown that late-onset depression is associated with larger deep white matter lesions (WMLs) and subcortical gray matter lesions (GMLs). In a longitudinal analysis, we examined changes in deep WMLs and subcortical GMLs in older depressed and nondepressed subjects over a 4-year period. METHODS: Brain magnetic resonance imaging (MRI) scans were obtained on 164 depressed and 126 healthy subjects aged 60 years or older at baseline, and 2 and 4 years after recruitment. WMLs and GMLs were measured using a semiautomated technique. We used repeated-measures analysis of covariance to determine cross-sectional lesion volume differences, whether lesion volume changes differed between patients and controls, and the effect of lesion volume changes on outcome in late-life depression. RESULTS: Mean volumes of lesions for the depressive group were 6.51, 8.18 and 7.75 cm2 for WMLs and 0.23, 0.30 and 0.34 cm2 for GMLs at baseline, 2-year and 4-year follow-up, respectively. Mean volumes of lesions for the control group were 4.83, 6.22 and 6.45 cm2 for WMLs and 0.17, 0.25 and 0.23 cm2 for GMLs at baseline, 2-year and 4-year follow-up, respectively. Cross-sectional between-group mean lesion volumes were significantly different for each measure. However, the pattern of WML and GML volume changes over time was not significantly different between groups. Treatment outcome was associated with changes in total and white matter lesion volume over time. CONCLUSIONS: Lesion volume progression is associated with aging and the pathological condition of late-life depression. The mechanisms that produce these progressive lesion changes remain unclear. Treatments aimed at arresting lesion progression may play a role in the management of late-life depression.

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PubMed2006

Cognitive function in late life depression: relationships to depression severity, cerebrovascular risk factors and processing speed.

BACKGROUND: A number of studies have examined clinical factors linked to worse neuropsychological performance in late life depression (LLD). To understand the influence of LLD on cognition, it is important to determine if deficits in a number of cognitive domains are relatively independent, or mediated by depression- related deficits in a basic domain such as processing speed. METHODS: Patients who met DSM-IV criteria for major depression (n = 155) were administered a comprehensive neuropsychological battery of tasks grouped into episodic memory, language, working memory, executive function, and processing speed domains. Multiple regression analyses were conducted to determine contributions of predictor variables to cognitive domains. RESULTS: Age, depression severity, education, race and vascular risk factors all made significant and independent contributions to one or more domains of cognitive function, with all five making independent contributions to processing speed. Age of onset made no independent contribution, after accounting for age and vascular risk factors. Of the five cognitive domains investigated, changes in processing speed were found to most fully mediate the influence of predictor variables on all other cognitive domains. CONCLUSIONS: While slowed processing speed appears to be the most core cognitive deficit in LLD, it was closely followed by executive function as a core cognitive deficit. Future research is needed to help clarify mechanisms leading to LLD- related changes in processing speed, including the potential role of white matter abnormalities.

Activities of Daily Living↗

PubMed2006

Perspectives on depression, mild cognitive impairment, and cognitive decline.

CONTEXT: The public health implications of depression and cognitive impairment in late life are enormous. Cognitive impairment and late-life depression are associated with increased risk for subsequent dementia; however, investigations of these phenomena appear to be proceeding along separate tracks. OBJECTIVES AND DATA SOURCE: The National Institute of Mental Health organized the conference "Perspectives on Depression, Mild Cognitive Impairment, and Cognitive Decline" to consider how the varied perspectives might be better integrated to examine the associations among depression, mild cognitive impairment, and cognitive decline and to illuminate the common or distinct mechanisms involved in these associations. DATA SYNTHESIS: The following 2 broad questions were addressed: (1) What gaps in our knowledge have the greatest public health significance? (2) Can we more efficiently use our research dollars and participant resources to fill these gaps? Meeting participants included grantees from the National Institute of Mental Health and the National Institute on Aging and program staff from the National Institute of Mental Health, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke. CONCLUSIONS: One of the most important recommendations to emerge from the meeting discussions is for increased collaboration among clinical and epidemiological investigators whose work focuses in the area of depression with those working primarily in the area of memory disorders. Directions for future research were identified.

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PubMed2006

White matter lesion volumes and caudate volumes in late-life depression.

BACKGROUND: Decreased caudate volumes and increased white matter lesions (WMLs) are associated both with aging and late-life depression, but the relationship between the two is unclear. We examined the association between WML and caudate volume, hypothesizing there would be a negative association, which would be stronger for WMLs located in anterior regions. We additionally hypothesized that this association would be stronger in depressed subjects. METHOD: This MRI study included 182 elderly depressed and 64 elderly control subjects. Our imaging analysis procedures divided the brain into anterior and posterior halves. WML volume in each half was calculated, as were left and right caudate volumes. A statistical model incorporating WML volumes, age, total brain volume, diagnosis, and gender was used to examine caudate volumes. RESULTS: WML volume was negatively associated with total and right caudate volume. This association was stronger for WMLs in the anterior half of the brain. Anterior WML volume was additionally negatively associated with right caudate volume in depressed subjects, but not in controls. CONCLUSIONS: Using unadjusted levels of significance, WML volume is negatively associated with right caudate volume in both older populations, but with left caudate volume only in depressed individuals. When statistical corrections for multiple comparisons are used, the finding is limited to a negative association between WML volume and right caudate volume, primarily in depressed subjects. This study demonstrates one mechanism by which WMLs may disrupt frontostriatal circuits.

Age of Onset↗

PubMed2006

Gender differences in the association between religious involvement and depression: the Cache County (Utah) study.

We examined the relation between religious involvement, membership in the Church of Jesus Christ of Latter-Day Saints, and major depression in a population-based study of aging and dementia in Cache County, Utah. Participants included 4,468 nondemented individuals between the ages of 65 and 100 years who were interviewed in person. In logistic regression models adjusting for demographic and health variables, frequent church attendance was associated with a reduced prevalence of depression in women but increased prevalence in men. Social role loss and the potential impact of organizational power differential by sex are discussed. Though causality cannot be determined here, these findings suggest that the association between religious involvement and depression may differ substantially between men and women.

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PubMed2006

Depression treatment preferences in older primary care patients.

PURPOSE: For depressed older primary care patients, this study aimed to examine (a) characteristics associated with depression treatment preferences; (b) predictors of receiving preferred treatment; and (c) whether receiving preferred treatment predicted satisfaction and depression outcomes. DESIGN AND METHODS: Data are from 1,602 depressed older primary care patients who participated in a multisite, randomized clinical trial comparing usual care to collaborative care, which offered medication and counseling for up to 12 months. Baseline assessment included demographics, depression, health information, prior depression treatment, potential barriers, and treatment preferences (medication, counseling). At 12 months, services received, satisfaction, and depression outcomes were assessed. RESULTS: More patients preferred counseling (57%) than medication (43%). Previous experience with a treatment type was the strongest predictor of preference. In addition, medication preference was predicted by male gender and diagnosis of major depression (vs dysthymia). The collaborative care model greatly improved access to preferred treatment, especially for counseling (74% vs 33% in usual care). Receipt of preferred treatment did not predict satisfaction or depression outcomes; these outcomes were most strongly impacted by treatment condition. IMPLICATIONS: Many depressed older primary care patients desire counseling, which is infrequently available in usual primary care. Discussion of treatment preferences should include an assessment of prior treatment experiences. A collaborative care model that increases collaboration between primary care and mental health professionals can increase access to preferred treatment. If preferred treatment is not available, collaborative care still results in good satisfaction and depression outcomes.

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PubMed2006

Cognitive impairment and depression outcomes in the IMPACT study.

INTRODUCTION: It is unclear whether cognitive impairment affects acute and long-term treatment response in geriatric depression. In addition, little is known about the long-term outcome of depression among older individuals who experience cognitive decline during a course of treatment for depression. The authors examined both of these issues using data from the IMPACT trial. METHODS: The sample consisted of 1,684 participants in the IMPACT study who had baseline and two-year follow-up data. Subjects were randomized to one year of active intervention with a depression care manager or usual care. After one year, all subjects had usual care for another year. Data were collected for two years. The authors used the Six-Item Cognitive Screener to examine acute and long-term effects on depression outcome of baseline cognitive impairment and of cognitive decline. Depression measures included the HSCL-20 and an estimation of depression-free days. Outcomes were determined using both linear regression and repeated-measures analyses. RESULTS: Depressed subjects in the active intervention group had better depression outcomes at one year regardless of baseline cognitive impairment. Cognitively impaired subjects within each treatment group had similar outcomes to subjects without cognitive impairment. Subjects who experienced decline in cognitive score over two years had worse 24-month depression outcomes compared with subjects whose cognitive score did not change. CONCLUSIONS: Cognitively impaired depressed patients can experience significant improvement in depression with appropriate acute and continuation-phase management. Older depressed adults experiencing ongoing cognitive decline may be at higher risk for poor depression outcomes and may require more careful clinical monitoring and management of both cognitive and affective symptoms.

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PubMed2006

Three-year incidence of first-onset depressive syndrome in a population sample of older adults: the Cache County study.

OBJECTIVE: Estimates of incidence of late-life depression vary greatly with few studies excluding demented cases through in-depth evaluation and most studies failing to control for the effect of mortality and interval treatment. In a large population-based study, the authors examined the effect on incidence of first-onset depressive syndrome to determine whether any gender or age differences in incidence are attenuated with inclusion of these additional measures. METHOD: Incidence rates of depressive syndrome per 1,000 person-years are presented for 2,877 nondemented elderly (ages 65 to 100 years) residents of Cache County, Utah. Cases are identified by direct interview methods, by inference from prescription antidepressant medicine use, and by postmortem informant interview for decedents. RESULTS: In-person interviews yielded incidence rates of first-onset depressive disorder (any type) of 13.09 for men and 19.44 for women. Inclusion of antidepressant users increased these figures to 15.55 for men and 23.30 for women. Addition of postmortem interview data yielded rates of 20.66 for men and 26.29 for women. Individuals with no history of depression had rates for major depression of 7.88 for men and 8.75 for women; minor depression rates were 19.23 for men and 24.46 for women (p = 0.691; effect for minor depression p <0.0001). Age did not predict incidence. CONCLUSIONS: Incidence of first-onset major depression varies with data source and prior lifetime history of depression. Gender effects apparent in interview data are attenuated when postmortem information and pharmacotherapy were considered.

Age Factors↗