PubMed Health⌕ Search

Biomedical subjects

L E Tune

Publications and source records attributed to L E Tune.

At least 19 recordsLinked to original sources
PubMed2001

Anticholinergic effects of medication in elderly patients.

Anticholinergic toxicity is a common problem in the elderly. It has many effects ranging from dry mouth, constipation, and visual impairments to confusion, delirium, and severe cognitive decline. The toxicity is often the result of the cumulative anticholinergic burden of multiple prescription medications and metabolites rather than of a single compound. The management of elderly patients, particularly those suffering from dementia, should therefore aim to reduce the use of medications with anticholinergic effects.

Aged↗
PubMed2001

Risperidone for the treatment of behavioral and psychological symptoms of dementia.

Risperidone offers physicians the unique combination of extensive, published clinical experience and a good safety profile for treating patients with dementia who have symptoms of aggression, agitation, and psychosis. Numerous open-label and, more recently, placebo-controlled trials have documented the efficacy of risperidone in the management of behavioral and psychological symptoms of dementia. These trials also show that risperidone is better tolerated than conventional neuroleptic agents. Comparatively, patients treated with risperidone experience substantially fewer side effects, including extrapyramidal symptoms, cognitive toxicity, and tardive dyskinesia.

Aged↗
PubMed2000

Alterations in the functional anatomy of working memory in adult attention deficit hyperactivity disorder.

OBJECTIVE: The authors used a functional neuroimaging study with a working memory probe to investigate the pathophysiology of attention deficit hyperactivity disorder (ADHD). Their goal was to compare regional cerebral blood flow (rCBF) changes related to working memory in adults with and without ADHD. METHOD: Using [(15)O]H(2)O positron emission tomography (PET) studies, the authors compared the sites of neural activation related to working memory in six adult men diagnosed with ADHD and six healthy men without ADHD who were matched in age and general intelligence. RESULTS: Task-related changes in rCBF in the men without ADHD were more prominent in the frontal and temporal regions, but rCBF changes in men with ADHD were more widespread and primarily located in the occipital regions. CONCLUSIONS: These data suggest the use of compensatory mental and neural strategies by subjects with ADHD in response to a disrupted ability to inhibit attention to nonrelevant stimuli and the use of internalized speech to guide behavior.

Adult↗
PubMed2000

Serum anticholinergic activity levels and delirium in the elderly.

This article will briefly review the clinical studies focusing on measurement of serum levels of anticholinergic activity in delirious states. Three experimental approaches have been taken. First, to identify medications currently prescribed that have subtle anticholinergic effects. The current "list" includes 48 commonly prescribed medications. Second, to associate serum anticholinergic activity with delirium in various clinical states including postcardiotomy delirium, postelectroconvulsive delirium, delirious elderly medical inpatients, and nursing home patients. Third, to intervene in patients with elevated anticholinergic activity by reducing known anticholinergics and correlating this reduction with clinical measures of cognition and delirium. Our most recent data investigate the impact of anticholinergics on demented patients. Prevalence of delirium was significantly higher in patients receiving larger numbers of anticholinergics.

Acetylcholine↗
PubMed1998

New cholinergic therapies: treatment tools for the psychiatrist.

This article reviews the current status of therapy with acetylcholine-enhancing compounds in the management of patients with Alzheimer's disease. The focus is on pivotal articles investigating the role of cholinergic augmentation strategies, including precursor loading and acetylcholinesterase (AChE) inhibitors, in the management of cognitive and noncognitive symptoms of Alzheimer's disease. Precursor loading strategies have been for the most part unimpressive. By contrast, studies with AChE inhibitors--tacrine and donepezil--have been promising. For patients in whom hepatotoxicity and gastrointestinal side effects were not problematic, tacrine improves cognitive performance and selected secondary psychiatric symptoms and significantly delays nursing home placement. Donepezil, recently approved for use in mild to moderate Alzheimer's disease, appears to be less toxic and better tolerated than tacrine. It improves performance on cognitive testing and, in one preliminary investigation, demonstrated a sustained drug effect over several years. Therapy with AChE inhibitors provides modest significant symptomatic improvement in patients with mild to moderate Alzheimer's disease.

Alzheimer Disease↗
PubMed1998

Depression and Alzheimer's disease.

Depressive symptoms, due either major depression or clinically significant, subsyndromal depression, occur commonly in the course of Alzheimer's disease. For a variety of clinical and methodological reasons, this remains an area that begs for new investigation. At the very least, these depressive symptoms should be viewed as a cause of significant and treatable "excess disability" (Kramer and Reifler, 1992). Demented patients with clinically significant depression (e.g., depressed mood, significant loss of appetite, insomnia, fatigue, irritability, and agitation) should be considered for a trial of antidepressant therapy, even when they fail to meet full diagnostic criteria for major depression. These symptoms will, in most instances, respond to antidepressant therapy. The "rules" for treatment of depression in dementia are slightly different than for cognitively intact patients: (a) start low, go slower, (b) pay attention to cognitive toxicity of all medication combinations, and (c) depressive symptoms do not persist as long as in cognitively intact patients. Current treatments, especially those SSRI's like fluoxetine and sertraline that have cognitive enhancing effects, should be considered the "first line" antidepressants. We need to emphasize early detection and treatment of depressive symptoms in dementia in all arenas.

Alzheimer Disease↗
PubMed1997

Quantitative MRI volume changes in late onset schizophrenia and Alzheimer's disease compared to normal controls.

Volumes of medial and lateral temporal lobe structures were assessed using magnetic resonance imaging (MRI) in 11 patients with late-life onset schizophrenia (LOS), 18 normal elderly controls and 12 patients with moderate cognitive impairment due to Alzheimer's disease (AD) who had no non-cognitive symptoms. While both patient groups had smaller volumes of several medial temporal regions (e.g. entorhinal cortex, left hippocampus), schizophrenics had significantly smaller anterior superior temporal gyri (STG) than normal controls, but AD patients did not. We have previously demonstrated anterior STG volume to be reduced in early life onset schizophrenia.

Age of Onset↗
PubMed1997

Quantification of neuroreceptors in the living human brain: IV. Effect of aging and elevations of D2-like receptors in schizophrenia and bipolar illness.

In a previous study of 10 drug-naive schizophrenic patients, the density of D2 dopamine receptors was found to be elevated in the caudate nucleus. The study raised questions about the influence of the age of the patients, the relationship of receptor density to psychosis, and the accuracy of the method used to obtain this evidence. Using positron emission tomography and constrained analysis of the brain uptake of the radioligand N-[11C]methyl-spiperone ([11C]NMSP), we tested four questions: Were the assumptions underlying the quantitation valid? Is there an age decline of the density of D2-like dopamine receptors in drug-naive schizophrenia and bipolar illness? If so, is it different from that observed in normal aging? Are D2-like dopamine receptors elevated at any age in either drug-naive schizophrenic or psychotic bipolar illness patients? NMSP and haloperidol partition volumes and plasma protein fractions were not significantly different among patient groups and normal volunteers. The model-derived assay of radioligand metabolites in plasma was confirmed by high-performance liquid chromatography in the patient groups. D2-like dopamine receptors declined with age, and the slope did not differ significantly between the schizophrenic patients, bipolar affective illness patients, and normal controls. Taking the effect of age into account, increases in D2 dopamine receptor density were found in seven psychotic patients with bipolar affective illness compared with seven nonpsychotic patients and 24 control subjects as well as in 22 drug-naive schizophrenic patients compared with the 24 control subjects.

Adult↗
PubMed1996

Regional hypometabolism in Alzheimer's disease as measured by positron emission tomography after correction for effects of partial volume averaging.

Measurements of cerebral metabolism in patients with Alzheimer's disease (AD) using PET are artifactually depressed due to partial volume averaging of brain tissue activity with enlarged CSF spaces. To investigate the effects of correction for the expansion of CSF spaces on regional metabolic measures, as well as the correlations between neuropsychological test results and resting cerebral metabolism before and after partial volume correction, we applied an MRI-based method of partial volume correction to 18F-fluorodeoxyglucose (FDG)-PET data from eight patients diagnosed with probable AD and ten healthy elderly individuals. Before correction, the AD group had significantly lower cortex-to-cerebellum ratios in the posterior temporal, parietal, and frontal lobes in comparison to the control subjects. Partial volume correction of PET data resulted in 19 to 49% increases in regional activity in the AD group and 16 to 38% increases in the control group. The patients' persistence of significant hypometabolism in the frontal, posterior temporal, and parietal regions after partial volume correction suggests that a true reduction in regional cerebral glucose metabolism occurs in AD, even though its magnitude is a result of both metabolic reductions and the effects of atrophy. Partial volume correction of PET data in the AD group had a significant impact on the correlations between regional glucose metabolism and neuropsychological performance. These findings suggest that accounting for differential extent and distribution of cerebral atrophy in patients with AD and in healthy individuals may potentially improve our ability to interpret specific cognitive dysfunction in the context of the functional imaging data.

Aged↗
PubMed1995

In vivo D2 dopamine receptor density in psychotic and nonpsychotic patients with bipolar disorder.

BACKGROUND: A prior positron emission tomographic study from The Johns Hopkins University, Baltimore, Md, using N-methylspiperone labeled with carbon 11 reported elevated basal ganglia D2 dopamine receptor density (Bmax) values in neuroleptic-naive schizophrenic patients compared with controls. We have now extended these studies to include patients with bipolar disorder. METHODS: Patients with bipolar disorder (n = 14) either had never received neuroleptic medication or had been neuroleptic-free for more than 6 months, and they met DSM-III criteria for currently symptomatic affective disorder. Patients with bipolar disorder were compared with matched schizophrenic patients and normal controls. All received two positron emission tomographic scans, the second of which was preceded by oral administration of haloperidol lactate, to permit the calculation of D2 dopamine receptor Bmax. RESULTS: Diagnostic groups differed in Bmax by analysis of variance (P < .0001); post hoc tests showed higher Bmax values for psychotic patients with bipolar disorder and schizophrenic patients compared with normal controls and for schizophrenic patients and psychotic patients with bipolar disorder compared with nonpsychotic patients with bipolar disorder. Among patients with bipolar disorder, Bmax values correlated significantly with the severity of psychotic symptoms (r = .63) on the Present State Examination but not with the severity of nonpsychotic mood symptoms. CONCLUSIONS: We conclude that, like schizophrenic patients, patients with psychotic bipolar disorder have elevations of D2 dopamine receptor Bmax values and that such elevations in affective disorder are more closely associated with the presence of psychosis than with mood abnormality. Elevations in dopamine receptor values thus may occur in psychiatric states that are characterized by psychotic symptoms rather than being specific to schizophrenia.

Adult↗
PubMed1995

Serotonergic modulation of anticholinergic effects on cognition and behavior in elderly humans.

Cholinergic neurotransmission is thought to be modulated by serotonin as documented in animal and human studies. We examined the effects of the muscarinic antagonist scopolamine (0.4 mg IV) given alone or together with the serotonin mixed agonist/antagonist m-chlorophenylpiperazine (m-CPP, 0.08 mg/kg IV), and the selective 5-HT3 receptor antagonist ondansetron (0.15 mg/kg IV). Ten normal elderly volunteers each received five separate pharmacologic challenges (placebo, ondansetron, scopolamine, scopolamine+ondansetron, and scopolamine+m-CPP). Cognitive, behavioral, and physiologic variables were analyzed using repeated measures analysis of variance. The acute effects of scopolamine in certain cognitive, behavioral, and physiological measures were significantly exaggerated by the addition of m-CPP. Scopolamine's cognitive effects were unaffected by ondansetron at the dose tested, nor did ondansetron given alone affect basal cognitive performance. This pilot study suggests that the serotonin mixed agonist/antagonist m-CPP may influence cholinergic neurotransmission. The changes associated with the combination of scopolamine and m-CPP do not appear to be secondary to simple pharmacokinetic alterations and suggest a complex interaction between the cholinergic and serotonergic systems centrally.

Aged↗
PubMed1993

Dopamine D2 receptor density estimates in schizophrenia: a positron emission tomography study with 11C-N-methylspiperone.

Positron emission tomography (PET) with 11C-N-methylspiperone as the radioligand was carried out in 25 chronic schizophrenic patients to determine dopamine D2 receptor density estimates in the corpus striatum. The sample included 18 neuroleptic-naive and 7 neuroleptic-free patients. Dopamine D2 receptor density estimates (Bmax) were obtained using a two-scan/four-compartment model. The Bmax estimates for the entire group (33.39 +/- 3.43 pmole/g) were significantly elevated when compared with estimates for the control group (Bmax = 15.63 +/- 2.38). The Bmax values for the entire group of schizophrenic patients showed a significant decline as a function of age. The Bmax values were significantly related to duration of illness (y = 13.2 + 10.3795x - 0.7931x2; r = 0.48). Thirteen patients and seven control subjects were added to our original publication sample (Wong et al., 1986c). The patients' Bmax values, when adjusted for age and sex effects, were significantly different compared with those of control subjects. Clinical data from the entire group were compared with published data from other research groups that have estimated dopamine D2 receptor density using different radioligands and different methods of data analysis. Comparisons of the clinical characteristics of the published studies show significant differences in patient populations, suggesting that discrepancies among published studies may reflect, in part, heterogeneity among groups of schizophrenic patients. The D2 receptor abnormality described in this study may be a late manifestation of disease, and the implications of this observation are discussed.

Adult↗
PubMed1993

Quantitative D2 dopamine receptor PET and structural MRI changes in late-onset schizophrenia.

Late-onset schizophrenia (LOS) is likely a syndrome of diverse etiology. In a series of related studies, we compared LOS patients with normal controls, elderly patients with early-onset schizophrenia (EOS), and Alzheimer's disease patients, using magnetic resonance imaging (MRI) and neuroreceptor positron emission tomography measures, which had previously been reported to be abnormal in EOS. EOS and LOS patients showed similar MRI changes. LOS drug-naive patients had elevated Bmax (receptor density) values for dopamine D2 receptors compared with age and gender norms, a phenomenon previously reported by our group in young schizophrenia patients.

Aged↗
PubMed1992

Quantitative changes in mesial temporal volume, regional cerebral blood flow, and cognition in Alzheimer's disease.

Twenty-six patients with moderately severe Alzheimer's disease (AD) and 16 normal control subjects were studied using either quantitative magnetic resonance imaging (MRI) measures of mesial temporal atrophy (15 patients with AD and 16 normal control subjects) and/or quantitative radioactive iodine 123-N-isopropyl-iodoamphetamine single-photon emission computed tomography (SPECT) assessment of regional cerebral blood flow (20 patients with AD and eight normal control subjects). Nine individuals with AD and eight normal control subjects underwent both structural and functional imaging. On MRI, patients and controls were best discriminated using left amygdala and entorhinal cortex volumes, and on SPECT they were best discriminated by relative left temporoparietal cortex blood flow. Combining these MRI and SPECT measures yielded 100% discrimination. Relative left temporoparietal SPECT regional cerebral blood flow and left superior temporal gyral MRI volume correlated best with severity of cognitive deficit in patients with AD. Mesial temporal MRI atrophy exceeded generalized cerebral shrinkage. Both SPECT and MRI regional changes accorded with areas known to be affected by AD neuropathology.

Aged↗
PubMed1992

Sylvian fissure size in schizophrenia measured with the magnetic resonance imaging rating protocol of the Consortium to Establish a Registry for Alzheimer's Disease.

OBJECTIVE: Since previous work indicated smaller than normal temporal lobe structures in schizophrenic patients, the authors tested the hypothesis that this abnormality might be reflected in abnormally large sylvian fissures. METHOD: The subjects were 48 schizophrenic patients and 51 normal comparison subjects matched groupwise with regard to age and sex. CSF spaces (sylvian fissures, temporal lobe sulci, temporal horns, third ventricle, lateral ventricles, and superficial cerebral sulci) were visually assessed with the magnetic resonance imaging rating protocol of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). RESULTS: The sylvian fissures of the schizophrenic patients were found to be bilaterally wider than those of the comparison subjects. There were no other significant differences. CONCLUSIONS: Schizophrenic patients appear to have larger than normal sylvian fissures, which may reflect smaller superior temporal gyri.

Adolescent↗
PubMed1991

Postoperative delirium.

Postoperative delirium is a common syndrome that is often mistaken for other psychiatric conditions, particularly depression. Numerous investigators have found a clear convincing association between delirium and increased morbidity and mortality. For this reason, greater attention should be focused on accurate clinical diagnosis. In this article, pre- and postoperative risk factors are reviewed. Lastly, areas demanding immediate further investigation are identified. In particular, outcome studies with particular emphasis on the role of age and prior drug exposure are urgently needed.

Aged↗
PubMed1991

Benzodiazepine-induced and anticholinergic-induced delirium in the elderly.

Encompassing the range from subtle cognitive impairments to frank delirium, toxicity due to benzodiazepines and to anticholinergic-containing compounds is reviewed. For benzodiazepines, an extensive literature suggests that they impair immediate and delayed memory, psychomotor performance, and subjective complaints of station. This, in several studies, results in increased patient morbidity (e.g., increasing risk of hip fractures). Anticholinergic compounds are widely utilized in managing elderly patients, particularly nursing home residents. Toxicity from anticholinergic compounds, detected by anticholinergic drug levels, is significantly correlated with the presence and severity of delirium in a number of settings including postoperative patients and elderly nursing home residents. Possible means of identifying the syndrome by prediction of dose and type of medication, as well as by quantitative EEG, are reviewed.

Aged↗