Search PubMed⌕ Search

Biomedical subjects

T Sunderland

Publications and source records attributed to T Sunderland.

At least 145 records · Page 8Linked to original sources
PubMed1988

Direct assessment of activities of daily living in Alzheimer's disease. A controlled study.

The relationship between severity of dementia and performance in four experimental tasks was studied in nine patients with Alzheimer's disease and nine age-matched controls. The experimental tasks were developed in order to establish a direct measure of functional performance in common activities of daily living. In the Alzheimer's patients, significant but moderate positive associations were found between the Clinical Dementia Rating Scale (CDR), a comprehensive rating tool designed specifically for Alzheimer's disease, and performance on the experimental tasks. A significant correlation was also found between the results of the Short Portable Mental Status Questionnaire (SPMSQ), a less specific dementia assessment instrument, and the CDR but not between the SPMSQ and the performance measure. When compared to nine normal subjects matched for gender, age, and education, the cognitively impaired subjects required more assistance and time (P less than .01) in completing the tasks. The findings support the conclusion that severity of dementia and performance on activities of daily living tasks are related but distinct concepts and should be measured separately.

Activities of Daily Living↗
PubMed1988

High-dose naloxone in older normal subjects: implications for Alzheimer's disease.

The behavioral and cognitive effects of naloxone HCl, in doses of 5 micrograms/kg, 0.1 mg/kg, and 2.0 mg/kg administered as an IV bolus, were assessed in a double-blind, placebo-controlled, randomized study of eight normal subjects ranging in age from 44 to 74 years (mean 63). Naloxone produced mild behavioral effects with slight cognitive impairment after the 2.0 mg/kg dose only. The threshold, dose dependency, characteristics, and magnitude of these behavioral effects were similar to what has previously been reported in young normal subjects, but markedly different from those observed in patients with dementia of the Alzheimer type (DAT) matched in age to the current study sample. These data suggest that the metabolic fate of naloxone is not substantially affected by age within the range studied. The findings of this study provide further support for a role for endogenous opiate systems in the modulation of behavior and cognition, and suggest that the unusual behavioral sensitivity of patients with DAT to naloxone cannot be accounted for by the effect of age.

Adult↗
PubMed1988

Galanin immunoreactivity in human CSF: studies in eating disorders and Alzheimer's disease.

Galanin is a peptide which stimulates feeding behavior in animals and is found within those basal forebrain cholinergic neurons which degenerate in Alzheimer's disease. Galanin was measured in cerebrospinal fluid (CSF) by radioimmunoassay. The nature of the immunoreactivity was characterized chromatographically as authentic galanin. CSF galanin levels were determined in subjects with Alzheimer's disease, involutional depression, anorexia nervosa and bulimia. No differences between any diagnostic group and age and sex-matched controls were found.

Adolescent↗
PubMed1988

A new scale for the assessment of depressed mood in demented patients.

Twenty-one subjects with clinically diagnosed dementia of the Alzheimer type were rated on the Dementia Mood Assessment Scale, a new instrument intended to measure the severity of depressed mood in cognitively impaired patients. Ratings were based on direct observation and a semistructured interview of the patient. Interrater reliability was established. There were highly significant correlations between patients' scores on the instrument's 17-item depression subscale and their scores on global measures of depression and sadness. The potential usefulness of this new scale in assessing the severity of depression in demented patients longitudinally or under drug treatment conditions is discussed.

Adult↗
PubMed1988

Tranylcypromine compared with L-deprenyl in Alzheimer's disease.

The authors have previously reported mild improvement of behavior and cognition in a group of 17 nondepressed patients with dementia of the Alzheimer type (DAT) treated with two doses of L-deprenyl (10 and 40 mg/day). Seven of these patients subsequently received double-blind, placebo-controlled treatment with tranylcypromine. The patients experienced significant side effects, particularly orthostatic hypotension without compensatory pulse increase, during tranylcypromine treatment. These effects were more severe than those occurring during L-deprenyl treatment, and they occurred at substantially lower doses (mean dose, 16 mg/day). These data support the role of the inhibition of monoamine oxidase type A in the development of orthostatic hypotension in patients treated with monoamine oxidase inhibitors. They also raise the question of whether the observed sensitivity to monoamine oxidase inhibition is a function of age or disease. In either case, the greater toxicity of tranylcypromine makes inferences difficult regarding the relative efficacies of these drugs in treating patients with dementia of the Alzheimer type and may limit the potential usefulness of tranylcypromine in ameliorating some symptoms of this disease.

Aged↗
PubMed1987

Anticholinergic sensitivity in patients with dementia of the Alzheimer type and age-matched controls. A dose-response study.

We compared the cognitive and behavioral responses to three intravenous doses of scopolamine (0.1, 0.25, and 0.5 mg) and placebo of ten patients with dementia of the Alzheimer type (DAT) and ten age- and sex-matched elderly control subjects. The patients with DAT showed significant behavioral and cognitive but not physiologic changes at a lower scopolamine dose (0.25 mg) than did the normal elderly controls. Cognitive tests of new learning and semantic knowledge revealed significant impairments at the 0.25-mg scopolamine dose in the patients with DAT, while the responses of the control population were essentially unchanged. Behaviorally, mild euphoria, motor incoordination, and hostility occurred in the patients with DAT but not the controls at the 0.25-mg dose. These differences were unrelated to peripheral physiologic changes produced by the different scopolamine doses. These results indicate that central nervous system functions such as cognition and certain elements of behavior are more sensitive to temporary cholinergic blockade in patients with DAT than in normal age-matched controls. We review implications concerning the status of central cholinergic function in patients with DAT in light of neuropathologically demonstrated cholinergic system lesions in DAT.

Age Factors↗
PubMed1987

L-deprenyl in Alzheimer's disease. Preliminary evidence for behavioral change with monoamine oxidase B inhibition.

Since monoamine neurotransmitter disturbances exist in some cases of dementia of the Alzheimer's type (DAT), monoamine-enhancing drugs may ameliorate some symptoms of DAT. L-Deprenyl is a monoamine oxidase (MAO) inhibitor that is generally free of undesired effects. At low doses (10 mg/d) it selectively inhibits MAO-B, an enzyme whose level is elevated in the brains of patients with DAT who are studied post mortem. At higher doses it has more complex effects, including inhibition of MAO-A plus MAO-B. We administered 10 mg/d and 40 mg/d of L-deprenyl to 17 patients with DAT in a double-blind, placebo-controlled, serial treatment. Total Brief Psychiatric Rating Scale scores decreased significantly during 10-mg/d treatment, with decreases in measures of anxiety/depression, tension, and excitement. Approximately one half of the patients' conditions were judged to be improved clinically, with evidence of increased activity and social interaction along with reduced tension and retardation. Similar but smaller changes were observed during 40-mg/d treatment. The behavioral changes were associated with improvement in performance on a complex cognitive task requiring sustained effort. There were minimal physiologic and side effects. The greater effect of low-dose L-deprenyl therapy suggests that it is the inhibition of MAO-B, and not MAO-A, that may be important in the behavioral effects of L-deprenyl administration to patients with DAT.

Adult↗
PubMed1987

Cognitive effects of L-deprenyl in Alzheimer's disease.

Monoamine neurotransmitter systems, along with cholinergic systems, are known to play important roles in cognition, and are disrupted in at least some patients with dementia of the Alzheimer type (DAT). This suggests that monoamine-enhancing drugs might ameliorate cognitive symptoms in certain patients with DAT. L-Deprenyl is a monoamine oxidase (MAO) inhibitor which may selectively inhibit MAO-B at low doses, while at high doses it nonselectively inhibits MAO-A as well as MAO-B. We studied its effects on several types of cognitive function in 17 patients with DAT. Two doses of L-deprenyl (10 mg/day and 40 mg/day) and placebo were compared in a double-blind, serial treatment design. Episodic learning and memory, knowledge memory, attention, recognition, and performance on a continuous performance task were assessed at baseline and under these drug and placebo conditions. Statistically significant improvement was noted in performance on an episodic memory and learning task requiring complex information processing and sustained conscious effort during treatment with L-deprenyl 10 mg/day. Knowledge memory, intrusions, and other cognitive functions relevant to DAT were not altered by L-deprenyl at either dose.

Adult↗
PubMed1987

Dose-dependent effects of deprenyl on CSF monoamine metabolites in patients with Alzheimer's disease.

Deprenyl, a monoamine oxidase (MAO) inhibitor with selective effects on MAO type-B at low doses, was administered to 13 patients with dementia of the Alzheimer type (DAT), a disorder reported to be associated with increased brain MAO-B activity. Cerebrospinal fluid was obtained for measurement of three monoamine metabolites, homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), by high pressure liquid chromatography with electrochemical detection. Deprenyl treatment (10 mg/day) for 3-4 weeks was associated with small but statistically significant reductions in HVA (21%) and 5-HIAA (15%) compared to baseline values. Subsequent administration of deprenyl at the higher dose of 40 mg/day for 3-4 more weeks led to greater reductions in HVA (40%) and MHPG (43%) than 5-HIAA (20%). These dose-dependent reductions are consistent with in vitro biochemical and anatomical data from primate brain suggesting that at low doses of deprenyl, MAO-B inhibition might be expected to selectively affect dopamine and serotonin-containing neurons, while at higher doses (which lead to MAO-A as well as MAO-B inhibition), noradrenergic neurons may become relatively more affected by the drug.

Aging↗
PubMed1987

Blood to brain distribution of neuroleptics.

Knowledge of the tissue distribution of drugs is important in interpreting other more commonly measured pharmacokinetic parameters, such as levels of drug in blood. For the neuroleptics, studies of blood to brain distribution are few and, due to technical differences between studies, the results are neither consistent within drugs nor comparable between drugs. We estimated the plasma to brain distribution of several common neuroleptics in rats using a single technique, the radioreceptor assay for neuroleptics. At doses that led to plasma levels similar to those achieved in clinical use, brain to plasma ratios ranged from 34 and 22 for fluphenazine and haloperidol, respectively, to 2.2 and 0.97 for thioridazine and mesoridazine, respectively. In general, clinical milligram potency and the favorability of distribution to brain ranked in the same order. These results may explain why such low levels of the high potency neuroleptics and such high levels of the low potency neuroleptics, greater than can be explained by relative differences between the same drugs in potency in vitro, are observed in blood both by radioreceptor and chemical assay techniques.

Animals↗
PubMed1987

The effects of antidepressants on the cerebrospinal fluid homovanillic acid/5-hydroxyindoleacetic acid ratio.

Dopamine and serotonin systems are morphologically interconnected in the midbrain. Several studies have also demonstrated a functional relationship between these two monoamine systems. Concentrations of their metabolites, 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA), consistently correlate with one another in human cerebrospinal fluid. Previous studies of the effects of antidepressants on the dopamine and serotonin systems have focused on the two systems in isolation without considering the interactions between the two. One way of taking this interaction into account may be to form a ratio of dopamine and serotonin measures. The present study measured HVA and 5HIAA in cerebrospinal fluid of 31 patients with depression and 12 patients with Alzheimer's disease before and after treatment with a variety of antidepressant drugs. The ratio of HVA/5HIAA was able to discriminate much more powerfully between effects of different drugs than HVA or 5HIAA examined separately.

Alzheimer Disease↗
PubMed1987

CSF somatostatin in patients with Alzheimer's disease, older depressed patients, and age-matched control subjects.

Somatostatin-like immunoreactivity was measured in the CSF of 12 patients with Alzheimer's disease, 15 age-matched control subjects, and 20 older depressed subjects. Patients with dementia or depression were found to have lower CSF somatostatin concentrations than control subjects despite markedly different clinical presentations. Severity of depression was clearly different in all three groups but showed no significant correlation with CSF concentration of somatostatin. There was a significant positive correlation between CSF somatostatin-like immunoreactivity and cognitive functioning in all 47 subjects, but this association was not statistically significant within individual diagnostic groups. These data raise interesting questions about possible biological links between Alzheimer's disease and depression in older patients.

Age Factors↗