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Biomedical subjects

Bruce G Pollock

Publications and source records attributed to Bruce G Pollock.

At least 55 records · Page 3Linked to original sources
PubMed2004

The nature and determinants of neuropsychological functioning in late-life depression.

CONTEXT: Cognitive impairment in late-life depression (LLD) is highly prevalent, disabling, poorly understood, and likely related to long-term outcome. OBJECTIVES: To determine the characteristics and determinants of neuropsychological functioning LLD. DESIGN: Cross-sectional study of groups of LLD patients and control subjects. SETTING: Outpatient, university-based depression research clinic. PARTICIPANTS: One hundred patients without dementia 60 years and older who met DSM-IV criteria for current episode of unipolar major depression (nonpsychotic) and 40 nondepressed, age- and education-equated control subjects. MAIN OUTCOME MEASURES: A comprehensive neuropsychological battery. RESULTS: Relative to control subjects, LLD patients performed poorer in all cognitive domains. More than half exhibited significant impairment (performance below the 10th percentile of the control group). Information processing speed and visuospatial and executive abilities were the most broadly and frequently impaired. The neuropsychological impairments were mediated almost entirely by slowed information processing (beta =.45-.80). Education (beta =.32) and ventricular atrophy (beta =.28) made additional modest contributions to variance in measures of language ability. Medical and vascular disease burden, apolipoprotein E genotype, and serum anticholinergicity did not contribute to variance in any cognitive domain. CONCLUSIONS: Late-life depression is characterized by slowed information processing, which affects all realms of cognition. This supports the concept that frontostriatal dysfunction plays a key role in LLD. The putative role of some risk factors was validated (eg, advanced age, low education, depression severity), whereas others were not (eg, medical burden, age at onset of first depressive episode). Further studies of neuropsychological functioning in remitted LLD patients are needed to parse episode-related and persistent factors and to relate them to underlying neural dysfunction.

Age Factors↗
PubMed2004

Serotonin modulation of cerebral glucose metabolism in normal aging.

Age-related alterations in serotonin function may increase the vulnerability to psychiatric and neurodegenerative disorders in late life. The neuroendocrine and cerebral metabolic response to the acute administration of the selective serotonin reuptake inhibitor, citalopram (40mg, IV), was measured in 17 normal control subjects using positron emission tomography (PET) to evaluate changes in serotonin function with normal aging. The citalopram-induced change in cerebral metabolism was positively correlated with age in the right precuneus, right paracentral lobule, and left middle temporal gyrus and negatively correlated with age in the left anterior cingulate gyrus, right inferior and middle frontal gyri, right insula, and right inferior parietal lobule. The positive correlations in mainly posterior brain regions indicate that normal aging is associated with an increase in metabolism after citalopram administration, whereas the negative correlations in mainly anterior brain regions indicate that normal aging is associated with a greater decrease in metabolism. These results suggest different compensatory processes in anterior compared to posterior brain regions secondary to the age-related loss of serotonin innervation.

Adult↗
PubMed2004

Effects of serotonin transporter promoter polymorphisms on serotonin function.

The serotonin transporter promoter polymorphism (5-HTTLPR) has been associated with vulnerability to stress-induced depressive symptoms and with the speed and rate of response to antidepressant treatment. The goal of the present study was to evaluate the association between the 5-HTTLPR and the functional response of the serotonin system as measured by the neuroendocrine and cerebral metabolic response to intravenous administration of the selective serotonin reuptake inhibitor citalopram in normal control subjects. Genotyping was performed for 5-HTTLPR insertion/deletion polymorphism long (l) and short (s) variant alleles. The ll genotype was compared with the combined sl+ss and with the ss genotype alone. Citalopram plasma concentrations did not differ significantly between groups. The s allele was associated with a less of an increase in prolactin and cortisol than the ll genotype. The s allele was associated with greater decreases in left frontal, precentral and middle temporal gyri compared to the ll genotype. The ll genotype was associated with greater decreases in right frontal, insula and superior temporal gyrus compared to the ss genotype. These findings suggest that 5-HTTLPR is associated with an altered functional response of the serotonin system, which may represent a neurobiologic substrate for the differential response to antidepressant treatment in late life and the emergence of neuropsychiatric symptoms in neurodegenerative disorders.

Adult↗
PubMed2004

Neuropathologic correlates of late-onset major depression.

Late life major depression (LLMD) is frequently associated with cognitive impairment, and increases the risk for subsequent dementia. Cerebrovascular disease, Alzheimer's disease (AD), and dementia with Lewy bodies (DLB) have all been hypothesized to contribute to this increased risk, though prospective studies have yet to examine these hypotheses with autopsy confirmation of the clinical diagnoses. The aim of this study is to examine the rates of cerebrovascular, AD, and DLB pathology among the first 10 participants in an LLMD brain tissue donation program. Subjects' psychiatric diagnoses and cognitive status were prospectively determined during their participation in clinical research protocols of the Intervention Research Center for Late Life Mood Disorders. After death, final clinical diagnoses were made using all clinical information, while blind to neuropathologic diagnoses. Neuropathologic assessments were conducted blind to final clinical diagnoses. Rates of neuropathology were compared with those in a cohort of subjects with dementia, without a history of LLMD, participating in an Alzheimer Disease Research Center. Seven (70%) subjects had evidence of onset of a dementia prior to death. LLMD with dementia was significantly associated with a neuropathologic diagnosis of AD. Cerebrovascular disease and DLB pathology were also frequent in the LLMD subjects with dementia, and were found in an LLMD subject without dementia. Rates of AD, DLB, and cerebrovascular disease were similar to those in the comparison subjects. These preliminary findings suggest that AD is the predominant neuropathologic condition in LLMD subjects with dementia. Further assessment of the role of comorbid cerebrovascular disease and comorbid DLB is needed.

Adult↗
PubMed2004

Meta-analysis of serotonin transporter polymorphisms and affective disorders.

Polymorphisms in the promoter region (5-HTTLPR) of the serotonin transporter and a variable number of tandem repeats polymorphism in the second intron have been widely studied. However, the results of association studies examining unipolar depression (MDD) or bipolar disorder depression (BPD) have been mixed. To precisely ascertain small associations with both polymorphisms, a meta-analysis was performed involving several thousand subjects, using random-effects modeling. For MDD, the effect of the 5-HTTLPR genotype was significant (chi2=6.1, P<0.05), with 21% of MDD subjects and 17% of controls homozygous for the short (S) allele (odds ratio, 1.16). Similar findings were noted in BPD, with a higher frequency of S/S genotypes in affected patients, although the results did not reach statistical significance. Results of transmission disequilibrium tests trended in a similar direction but also did not reach statistical significance. No consistent effect of the variable number of tandem repeats polymorphism was revealed for either MDD or BPD. The results suggest that the S allele, or a neighboring allele in linkage disequilibrium, is recessive for MDD and possibly BPD. Notably, the association is very small. With these small associations, confounding issues such as population stratification require addressing. Significant heterogeneity between studies was also evident, possibly reflecting differences in diagnosis, different control populations, and different ethnic populations. These factors should Influence the interpretation of the association found in this analysis.

Bipolar Disorder↗
PubMed2004

Antidepressant pharmacotherapy in the treatment of depression in the very old: a randomized, placebo-controlled trial.

OBJECTIVE: This study determined the efficacy of antidepressant medication for the treatment of depression in the "old-old." METHOD: This randomized 8-week medication trial compared citalopram, 10-40 mg/day, to placebo in the treatment of patients 75 and older with unipolar depression. RESULTS: A total of 174 patients who were 58% women with a mean age of 79.6 years (SD=4.4) and a mean baseline Hamilton Depression Rating Scale score of 24.3 (SD=4.1) were randomly assigned to treatment at 15 sites. There was a main effect for site but not for treatment condition. The remission rate, defined as a final Hamilton depression scale score <10, was 35% for the citalopram and 33% for the placebo groups. However, patients with severe depression (baseline Hamilton depression scale score >24) tended to have a higher remission rate with medication than with placebo (35% versus 19%). CONCLUSIONS: In the oldest group of community-dwelling patients to be studied to date, medication was not more effective than placebo for the treatment of depression. However, given the considerable psychosocial support received by all patients, the placebo condition represents more than the ingestion of an inactive pill. Across sites, there was considerable range in response to medication, 18% to 82%, and to placebo, 16% to 80%.

Age Factors↗
PubMed2004

Utility of sparse concentration sampling for citalopram in elderly clinical trial subjects.

The objective of this study was to evaluate whether the disposition of the selective serotonin reuptake inhibitor, citalopram, could be robustly captured using 1 to 2 concentration samples per subject in 106 patients participating in 2 clinical trials. Nonlinear mixed-effects modeling was used to evaluate the pharmacokinetic parameters describing citalopram's disposition. Both a prior established 2-compartment model and a de novo 1-compartment pharmacokinetic model were used. Covariates assessed were concomitant medications, race, sex, age (22-93 years), and weight. Covariates affecting disposition were assessed separately and then combined in a stepwise manner. Pharmacokinetic characteristics of citalopram were well captured using this sparse sampling design. Two covariates (age and weight) had a significant effect on the clearance and volume of distribution in both the 1- and 2-compartment pharmacokinetic models. Clearance decreased 0.23 L/h for every year of age and increased 0.14 L/h per kilogram body weight. It was concluded that hyper-sparse sampling designs are adequate to support population pharmacokinetic analysis in clinically treated populations. This is particularly valuable for populations such as the elderly, who are not typically available for pharmacokinetic studies.

Administration, Oral↗
PubMed2004

Correlates of anticholinergic activity in patients with dementia and psychosis treated with risperidone or olanzapine.

BACKGROUND: Older individuals with dementia are highly sensitive to the effects of muscarinic receptor blockade. STUDY DESIGN: This was a 6-week multisite, randomized clinical trial. SUBJECTS: Eighty-six patients with probable Alzheimer's disease, vascular dementia, or mixed-etiology dementia (DSM-IV criteria) were randomly assigned to treatment with olanzapine or risperidone. ASSESSMENTS: Anticholinergic activity was measured with a radioreceptor assay, and plasma levels of antipsychotic medications were determined. Primary outcomes were assessed with the Udvalg for Kliniske Undersogelser (UKU) scale and somnolence adverse events; secondary outcome measures included scores on the Neuropsychiatric Inventory (NPI) and other scales. RESULTS: There were no between-treatment differences in the UKU scale or in somnolence adverse events. Statistically significant improvements (p < .001) from baseline were found for the NPI measures, with no between-treatment group differences. Olanzapine was associated with significant increases from baseline in anticholinergic activity, while risperidone was not; the between-treatment group differences were not statistically significant. Increase in anticholinergic activity was associated with an increase in anticholinergic side effects and slower performance on the Trail Making Test Part A. Higher endpoint anticholinergic activity was associated with higher endpoint scores on several items from the NPI, including delusions, anxiety, and aberrant motor behavior. IMPLICATIONS: Efficacious doses of olanzapine increased anticholinergic activity in older patients with dementia, while similarly efficacious doses of risperidone did not. Patients whose anticholinergic activity increased were more likely to experience anticholinergic side effects and to have worsening in certain cognitive domains. These data suggest that certain patients may be vulnerable to the anticholinergic activity associated with antipsychotic treatment.

Antipsychotic Agents↗
PubMed2003

Serum anticholinergic activity in a community-based sample of older adults: relationship with cognitive performance.

BACKGROUND: Serum anticholinergic activity (SAA), as measured by a radioreceptor assay, quantifies a person's overall anticholinergic burden caused by all drugs and their metabolites. In several small geriatric patient groups, SAA has been associated with cognitive impairment or frank delirium. To our knowledge, there has not yet been any systematic study of the prevalence of SAA and its effect on cognition in a community-based population. METHODS: Serum anticholinergic activity was measured in 201 subjects who were randomly selected among the participants in an epidemiological community study, based on their age and sex. Cognitive performance was assessed with use of the Mini-Mental State Examination. The association between SAA and cognitive performance was examined using a univariate analysis and a multiple logistic regression model, adjusting for age, sex, educational level, and number of medications. RESULTS: Serum anticholinergic activity was detectable in 180 (89.6%) participants (range, 0.50-5.70 pmol/mL). Univariate testing showed a significant association between SAA and Mini-Mental State Examination scores. Logistic regression analysis indicated that subjects with SAA at or above the sample's 90th percentile (ie, SAA >/=2.80 pmol/mL) were 13 times (odds ratio, 1.08-152.39) more likely than subjects with undetectable SAA to have a Mini-Mental State Examination score of 24 (the sample's 10th percentile) or below. CONCLUSIONS: To our knowledge, this is the largest analysis of SAA and the first to examine its extent and relationship with cognitive performance in a community sample. Its results suggest that SAA can be detected in most older persons in the community and confirm that even low SAA is associated with cognitive impairment.

Age Factors↗
PubMed2003

Depression and Bipolar Support Alliance consensus statement on the unmet needs in diagnosis and treatment of mood disorders in late life.

OBJECTIVES: To review progress made during the past decade in late-life mood disorders and to identify areas of unmet need in health care delivery and research. PARTICIPANTS: The Consensus Development Panel consisted of experts in late-life mood disorders, geriatrics, primary care, mental health and aging policy research, and advocacy. EVIDENCE: (1) Literature reviews addressing risk factors, prevention, diagnosis, treatment, and delivery of services and (2) opinions and experiences of primary care and mental health care providers, policy analysts, and advocates. CONSENSUS PROCESS: The Consensus Development Panel listened to presentations and participated in discussions. Workgroups considered the evidence and prepared preliminary statements. Workgroup leaders presented drafts for discussion by the Consensus Development Panel. The final document was reviewed and edited to incorporate input from the entire Consensus Development Panel. CONCLUSIONS: Despite the availability of safe and efficacious treatments, mood disorders remain a significant health care issue for the elderly and are associated with disability, functional decline, diminished quality of life, mortality from comorbid medical conditions or suicide, demands on caregivers, and increased service utilization. Discriminatory coverage and reimbursement policies for mental health care are a challenge for the elderly, especially those with modest incomes, and for clinicians. Minorities are particularly underserved. Access to mental health care services for most elderly individuals is inadequate, and coordination of services is lacking. There is an immediate need for collaboration among patients, families, researchers, clinicians, governmental agencies, and third-party payers to improve diagnosis, treatment, and delivery of services for elderly persons with mood disorders.

Age Factors↗
PubMed2003

APOE is associated with age-of-onset, but not cognitive functioning, in late-life depression.

OBJECTIVE: There is a recognized but poorly understood relationship between late-life depression (LLD) and progressive dementia. Both cognitive impairment co-occurring with LLD and a late age-of-onset of first lifetime depressive episode appear to be associated with subsequent progressive dementia. A history of major depression, especially when the first onset occurs in late-life, has been identified as a risk factor for Alzheimer's disease (AD). The major genetic risk factor for sporadic AD is carrying one or more apolipoprotein E4 (APOE4) alleles. We hypothesized that the association between LLD and dementia risk would be mediated by APOE4, specifically that APOE4 allele frequency would be associated with cognitive impairment and later age-of-depression-onset. We also predicted that APOE4 allele frequency would be increased among subjects with LLD. METHODS: We compared the distribution of APOE2, APOE3, and APOE4 alleles in groups of LLD (n=160), AD (n=568) and elderly control (EC; n=156) subjects. RESULTS: The allele distribution of the cognitively impaired LLD subgroup was not different from either the cognitively normal subgroup or the EC group but was different from the AD group. However, mean age-of-onset of depression in APOE4 carriers (51.4+/-20.7) was significantly lower than non-carriers (58.8+/-16.8). The allele distribution in LLD overall was significantly different from the AD but not the EC group. CONCLUSIONS: The finding that neither LLD, accompanying cognitive impairment, nor late age-of-onset was associated with an increased APOE4 allele frequency suggests that LLD acts as a risk factor for developing AD as well as non-AD dementia through mechanisms independent of APOE4. The unexpected finding that age-of-onset of LLD was significantly reduced in APOE4 carriers is similar to the association between APOE4 and age-of-onset in AD. Replication of the association of APOE4 with earlier age-of-depression-onset is indicated.

Age of Onset↗
PubMed2003

Good treatment outcomes in late-life depression with comorbid anxiety.

BACKGROUND: Late-life depression studies have found that comorbid anxiety, as a symptom or comorbid disorder, is associated with poorer treatment response and increased likelihood of dropout. This study evaluated the impact of comorbid anxiety on response, dropouts, and side effects, in elderly subjects treated for depression. METHODS: We analyzed data from a 12-week trial comparing nortriptyline and paroxetine in 116 patients aged 60 and older with depression. Subjects classified as having anxious depression were compared to those with nonanxious depression in terms of treatment response rate, time to response, dropout rate, and early side effects. The analysis was replicated with another study, in which 125 subjects aged 69 and older were treated openly with paroxetine and interpersonal psychotherapy. RESULTS: Anxious and nonanxious groups did not differ in terms of response rates, time to response, dropout rates, or time to dropout. Side effects declined more quickly and more significantly in the anxious group than in the nonanxious group. LIMITATIONS: Subjects were treated in a specialty mental health setting, and the findings may not apply in other settings. CONCLUSIONS: We found no association between comorbid anxiety and a poorer prognosis during acute treatment of late-life depression. For elderly patients with anxious depression, standardized treatment in the mental health sector is associated with a good response.

Age of Onset↗
PubMed2003

Treatment considerations for anxiety in the elderly.

Anxiety is common in the elderly and can present as a primary anxiety disorder or as a symptom of another disorder. Generalized anxiety disorder, in particular, is a common syndrome in late life. Anxiety symptoms are also common features of late-life depression and dementia. Treatment of anxiety in elderly persons has typically involved the use of benzodiazepines, which are often effective but problematic because they are associated with increased risk of cognitive impairment, falls, and fractures. Based on their safety and efficacy, antidepressants, particularly serotonergic medications, are considered first-line treatment for most anxiety disorders as well as anxiety symptoms of major depressive disorder. Psychotherapy, particularly cognitive-behavioral therapy, may be effective in these disorders as well; research is underway to adapt this therapy to the needs of elderly persons. Anxiety symptoms in dementia are poorly understood but may respond to atypical antipsychotics, serotonergic antidepressants, or mood stabilizers. Overall, the research in late-life anxiety has not caught up to the literature in late-life depression and, for the most part, treatment recommendations must be extrapolated from studies in young adults.

Aged↗
PubMed2003

Achieving long-term optimal outcomes in geriatric depression and anxiety.

Depression and anxiety disorders are very common in the elderly. Data accumulated over the past 2 decades have shown that most older patients can tolerate and respond to acute treatment with serotonergic antidepressants, other psychotropic agents, or manual-based psychotherapy. However, outcomes under usual-care conditions remain poor. This review proposes that clinicians may significantly improve the long-term outcomes of their older patients with depression and anxiety by focusing on four key factors: (1) identification and treatment of comorbid conditions; (2) full remission of acute symptoms; (3) education of patients, families, and professional colleagues about the need for long-term treatment; and (4) prevention and management of medication side-effects.

Aged↗
PubMed2003

Influence of DHEA administration on 24-hour cortisol concentrations.

DHEA is marketed and readily available as a daily nutritional supplement to counteract the effects of aging. The effect of DHEA administration on 24-hour plasma cortisol profiles has not been investigated. In this single-blind placebo-controlled crossover study, the effect of DHEA administration on cortisol concentrations was evaluated in healthy older women and men. Once each morning, subjects took either placebo (Days 1 to 7, and 23 to 29) or oral DHEA 200 mg (Days 8 to 22: doses 1 to 15). Twenty-four hour DHEA and cortisol concentrations were measured on Day 1 (placebo), Day 8 (DHEA dose 1), Day 15 (DHEA dose 8), Day 22 (DHEA dose 15), and Day 29 (placebo washout dose 7). DHEA administration resulted in a decrease in plasma cortisol concentrations (mean, peak, and/or AUC) in healthy older women and men. The cortisol-lowering effect of DHEA was more pronounced in women than in men in our study; pairwise differences in concentrations between days showed that relative to Day 1, cortisol was lower on Days 15, 22, and 29 in women (p = 0.0001) and on Day 15 in men (p = 0.002). The mechanism by which DHEA lowers plasma cortisol concentrations merits further investigation.

Aged↗
PubMed2003

A preliminary study of the effect of fluoxetine treatment on the 2:16-alpha-hydroxyestrone ratio in young women.

Cytochrome P450 isoenzymes are known to contribute to estrone metabolism. The authors hypothesized that fluoxetine, a known inhibitor of multiple P450 isoenzymes including 3A4, 2C9, and 2D6, would affect estrone metabolism, altering the 2-hydroxyestrone:16-alpha-hydroxyestrone (2OHE1:16OHE1) ratio. In this preliminary study, four of eight recruited women with regular menstrual cycles, aged 21-37 years, completed a 24-hour urine collection prior to initiation of fluoxetine therapy and after at least 5 weeks of antidepressant treatment. In three of the four women who were nonsmokers, the 2OHE1:16OHE1 ratio was significantly higher after 5 weeks of fluoxetine therapy (pretreatment, 2.08 +/- 0.11; posttreatment, 3.50 +/- 0.46; paired Student's t-test P = 4.72, P = 0.021).

Adult↗
PubMed2003

Apathy and executive function in depressed elderly.

Apathy and executive cognitive dysfunction (ECD) are important though conceptually different aspects of late-life depression. The primary objective of this study was to evaluate the relationship of apathy to ECD. The authors also evaluated the relationship of apathy and ECD to global cognitive impairment and word generation. Fifty-two elderly subjects with major depression and MMSE scores of 15 or greater were evaluated with apathy-related items from the Hamilton rating scale for depression (ApHRSD), the Executive Interview (EXIT), the Dementia Rating Scale (DRS), and the Controlled Oral Word Association test (COWA). ApHRSD scores were not significantly correlated with any of these variables. EXIT scores were correlated significantly with DRS and COWA. The results suggest that apathy and ECD may be independent of each other in some samples of elderly with late-life depression. Correlations may have been reduced by low variance for the variables of interest and by psychometric limitations of the ApHRSD.

Aged↗