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Biomedical subjects

J Corwin

Publications and source records attributed to J Corwin.

At least 19 recordsLinked to original sources
PubMed1999

Acute effects of the selective cholinergic channel activator (nicotinic agonist) ABT-418 in Alzheimer's disease.

To explore further the potential for cognitive enhancement utilizing nicotinic stimulation in Alzheimer's disease (AD), six otherwise healthy subjects with moderate AD received placebo and three doses (6, 12, and 23 mg) of the novel selective cholinergic channel activator (ChCA) (nicotinic agonist) ABT-418 over 6 h in a double-blind, within-subjects, repeated-measures design. Subjects showed significant improvements in total recall and a decline in recall failure on a verbal learning task. Qualitatively similar improvements were seen in non-verbal learning tasks such as spatial learning and memory, and repeated acquisition. No significant behavioral, vital sign, or physical side effects were seen. These results confirm that stimulating central nicotinic receptors has acute cognitive benefit in AD patients. These findings suggest that selective ChCAs have a potential therapeutic role in dementing disorders, and that further studies with this or similar agents in AD and/or Parkinson's disease are warranted.

Aged↗
PubMed1998

Differential lateralization of memory discrimination and response bias in temporal lobe epilepsy patients.

Recognition memory for words and designs was assessed in epilepsy patients who underwent unilateral anterior temporal lobectomy. Memory was assessed during the intracarotid amobarbital test (IAT) performed prior to surgery and also following surgery. Memory discrimination and response bias lateralized differently. Memory discrimination, or memory accuracy, lateralized as a function of the type of material used in memory testing. Left temporal lobe lesions resulted in more impaired discrimination of verbal materials; right temporal lobe lesions resulted in more impaired discrimination of visuospatial materials. Response bias, the decision rule adopted in situations of uncertainty, was more liberal following left temporal lobe lesions for both verbal and visuospatial materials. Findings suggest that the two cerebral hemispheres are differentially specialized for encoding different types of information in long term memory, and that this impacts on decision strategies in situations of memory uncertainty.

Adult↗
PubMed1995

Workplace, age, and sex as mediators of olfactory function: data from the National Geographic Smell Survey.

Certain medications and environmental agents are known to adversely affect chemosensation. We report data from 712,000 respondents aged 20 to 79 to the National Geographic Smell Survey that suggest that exposure to the factory workplace adversely affects the sense of smell, and that these effects interact with age. Men and women with histories of factory work reported poorer senses of smell relative to other workers. They also demonstrated objective evidence of greater impairment in odor detection. These effects were greater for men. Factory workers of all ages more frequently reported olfactory loss secondary to chemical exposure and head injury than did workers in other environments. The highest relative risk of olfactory problems secondary to head injury was in the oldest women factory workers. Thus, olfaction may behave as other senses do: Age, sex, and exposure to noxious events or agents interact to produce sensory deficits.

Adult↗
PubMed1994

Age-related effects of the nicotinic antagonist mecamylamine on cognition and behavior.

Studies of the neurochemical pathology of Alzheimer's disease and Parkinson's disease reveal a severe and specific loss of central nicotinic cholinergic receptors. We have investigated the functional significance of this finding for cognitive functioning by studying the effects of the centrally active nicotinic antagonist mecamylamine. Single oral doses of mecamylamine were administered to 12 healthy young males and 15 healthy elderly subjects in doses of 5, 10, and 20 mg in a placebo-controlled, double-blind study. In both groups, the 20-mg dose caused a significant increase in errors in the learning condition of the Repeated Acquisition Task, producing a slower acquisition curve. There was no effect of drug on the performance component (retrieval of previously learned information). However, elderly subjects showed enhanced sensitivity to mecamylamine, with 10-mg dose producing significant impairment of learning not seen in the young normals. On a recognition memory task, there was an age-associated shift in response bias, with the elderly subjects becoming more liberal with increasing dose. Reaction-time measures suggested a dose-related slowing of reaction time on several tasks. Behavioral effects were minimal and physiologic effects were consistent with dose-related ganglionic blockade. These results indicate that acute blockade of nicotinic receptor function can produce measurable and significant cognitive impairment similar to some deficits seen in dementing illnesses, and that there is an age-related increase in sensitivity to nicotinic blockade.

Adult↗
PubMed1993

Olfactory identification deficits in Down's syndrome and idiopathic mental retardation.

We investigated olfactory identification in children and adults with Down's syndrome (DS) and idiopathic mental retardation (IMR) and in age-matched normal controls (NC). Identification was assessed with a four alternative-forced-choice task modified from the University of Pennsylvania Smell Identification Test (M-UPSIT) and a yes/no task yielding measures of discrimination and response bias for the same stimulus material. Control tactile identification tasks were also administered. Results were that odor identification performance on both tasks was specifically impaired in DS compared to IMR and NC. Accuracy of identification on the M-UPSIT correlated inversely with age in DS only. When uncertain, DS and IMR subjects guessed "yes" more often than "no" on the Yes/No task (liberal decision bias) and guessed the last response alternative on the M-UPSIT (recent position bias), whereas the normal subjects had neutral decision bias on the Yes/No task and matched the objective position presentation probabilities on the M-UPSIT. Decision bias correlated with accuracy of identification in both tasks for the DS subjects only.

Adolescent↗
PubMed1992

Acute nicotinic blockade produces cognitive impairment in normal humans.

Single oral doses of the central and peripheral nicotinic antagonist mecamylamine were administered to healthy young normal males in doses of 5, 10, and 20 mg in a placebo-controlled, double-blind study. The 20 mg dose caused a significant increase in errors in the learning condition of the Repeated Acquisition task, producing a slower acquisition curve. The lower doses produced less errors, but more than in the placebo condition. There was no effect of drug on the performance component (retrieval of previously learned information). On the recognition memory task, dose-related increases in false-alarms during the delay period were seen, with little effect on misses or hits. Reaction time measures suggested a dose-related slowing of RT on several tasks. Behavioral effects were minimal and physiologic measures were consistent with dose-related ganglionic blockade. We interpret these results to indicate that acute blockade of nicotinic receptor function can produce measurable and significant cognitive impairment, even in non-smoking normals.

Adult↗
PubMed1992

Is verbal recognition memory really different in Huntington's and Alzheimer's disease.

Verbal recall and recognition were examined in Huntington's disease (HD) and Alzheimer's disease (AD) patients. Subgroups of HD and AD patients were matched for overall severity of dementia. Subjects were administered the Hopkins Verbal Learning Test, a list-learning task with three free-recall trials followed immediately by one yes/no recognition trial with semantically related and unrelated distractors. The matched AD and HD groups did not differ in the number of words recalled, although the HD patients showed slightly greater improvement over trials. Recognition performance was evaluated with measures of accuracy and response bias that are independent of each other. The matched groups did not differ in overall recognition accuracy, but the AD patients tended to have a more liberal ("yea-saying") response bias than did the HD patients. In addition, only the AD patients were differentially enticed to false-positive responding by semantically related distractors. The results suggest that the rule for making decisions when uncertain, rather than memory strength per se, distinguishes the recognition memory performance of AD and HD patients.

Alzheimer Disease↗
PubMed1992

Life-sustaining interventions in frail elderly persons. Talking about choices.

BACKGROUND: Engaging older persons in consideration of use of life-sustaining measures, such as cardiopulmonary resuscitation, tube feeding, and urgent intubation, is widely recommended, yet uncommon. METHODS: We studied the short-term impact of a physician-initiated discussion, geared toward guiding informed decision-making, with 20 frail elderly homebound patients. A battery of psychologic rating scales was administered in a pre-post design. Eighteen subjects completed the protocol. Fifteen of the mentally capable surviving subjects were reinterviewed 18 months following the initial discussion to evaluate durability of their decisions. RESULTS: Most welcomed the discussion and clear choices regarding future care usually emerged. Depression rating scales decreased slightly for the entire sample. For the subgroup having relatively internal locus of control, there was an increase in life satisfaction scores. No patient demonstrated signs of emotional trauma consequent to the discussion. On follow-up, several patients were indecisive about their choices. CONCLUSION: Involvement of these patients in decision-making appeared to have no adverse effects, and, for some, it was therapeutic, possibly through enhancement of personal control. Durability of their decisions was not a consistent finding, however.

Advance Directives↗
PubMed1991

Disappearance of memory deficits in outpatient depressives responding to imipramine.

We evaluated learning and memory in 50 depressed patients prior to and following 4 week treatment with imipramine compared to 21 normal controls tested at corresponding times. At baseline, the depressives did worse than normals on most memory tasks with the difficult memory tasks, regardless of store, modality or type of task best distinguishing between depressive and normal memory. Following imipramine treatment, responders performed better than nonresponders on the difficult memory tasks, and not significantly differently from controls on most tasks. This, as well as the fact that the responders improved to a greater degree than controls on most measures (in a few cases the difference was statistically significant) and the fact that at 4 weeks complete responders to imipramine did significantly better than partial responders to imipramine, indicates that relief from depression is highly related to improved memory functioning. The finding that complete responders to imipramine were not significantly worse than normal controls suggests that imipramine did not have significant adverse effects on memory.

Adult↗
PubMed1990

Disorders of decision in affective disease: an effect of beta-adrenergic dysfunction?

We investigated response bias (defined as the decision rule subjects adopt when uncertain) in two experiments using a variant of Signal Detection Theory (SDT) with the discrimination measure d'L and the bias measure CL, under which it is possible to independently evaluate discrimination and response bias. In the first experiment, manics, depressed subjects, and matched psychiatrically normal controls were tested with a recognition memory task with easier and more difficult components before and after 1 month of appropriate pharmacological treatment. This experiment showed that abnormally conservative bias was characteristic of depression and liberal (yea-saying) bias was found in mania regardless of severity of illness; discrimination deficits were found only when symptoms were severe. After treatment, aspects of discrimination worsened in both hypomanic and depressed nonresponders whereas response bias remained unchanged in these patients. In both groups of responders, improvements in response bias were more dramatic than improvements in discrimination. In the second experiment, psychiatrically normal hypertensives were tested with a Sternberg short-term memory scanning task on and off treatment with the centrally active beta-blocker propranolol. This experiment showed that treatment with propranolol modeled the bias deficit of depression; that is, bias became more conservative. Both sets of results suggest that disorders of decision may be modulated by beta-adrenergic function.

Arousal↗
PubMed1989

Olfactory identification in hemodialysis: acute and chronic effects on discrimination and response bias.

The present experiment investigated the effects of renal failure and hemodialysis on olfactory identification and response bias assessed by a yes-no task administered both before and 1/2 hr after hemodialysis sessions. Identification and bias were measured under two theories. Results showed that dialysis patients had poorer identification ability overall than their controls which worsened after treatment. Patients' bias was more liberal than controls before treatment but became similar to the controls' afterwards; the bias measures Br and CL were differentially sensitive to diagnosis and time of testing effects. There was a dissociation between discrimination and bias changes in dialysis; patients' bias more closely resembled that seen in dementia (liberal) rather than depression (conservative).

Brain↗
PubMed1988

Pragmatics of measuring recognition memory: applications to dementia and amnesia.

This article has two purposes. The first is to describe four theoretical models of yes-no recognition memory and present their associated measures of discrimination and response bias. These models are then applied to a set of data from normal subjects to determine which pairs of discrimination and bias indices show independence between discrimination and bias. The following models demonstrated independence: a two-high-threshold model, a signal detection model with normal distributions using d' and C (rather than beta), and a signal detection model with logistic distributions and a bias measure analogous to C. C is defined as the distance of criterion from the intersection of the two underlying distributions. The second purpose is to use the indices from the acceptable models to characterize recognition memory deficits in dementia and amnesia. Young normal subjects, Alzheimer's disease patients, and parkinsonian dementia patients were tested with picture recognition tasks with repeated study-test trials. Huntington's disease patients, mixed etiology amnesics, and age-matched normals were tested by Butters, Wolfe, Martone, Granholm, and Cermak (1985) using the same paradigm with word stimuli. Demented and amnesic patients produced distinctly different patterns of abnormal memory performance. Both groups of demented patients showed poor discrimination and abnormally liberal response bias for words (Huntington's disease) and pictures (Alzheimer's disease and parkinsonian dementia), whereas the amnesic patients showed the worst discrimination but normal response bias for words. Although both signal detection theory and two-high-threshold discrimination parameters showed identical results, the bias measure from the two-high-threshold model was more sensitive to change than the bias measure (C) from signal detection theory. Three major points are emphasized. First, any index of recognition memory performance assumes an underlying model. Second, even acceptable models can lead to different conclusions about patterns of learning and forgetting. Third, efforts to characterize and ameliorate abnormal memory should address both discrimination and bias deficits.

Adult↗
PubMed1988

Perceptual identification thresholds for 150 fragmented pictures from the Snodgrass and Vanderwart picture set.

This paper reports perceptual identification thresholds for 150 pictures from the 1980 Snodgrass and Vanderwart picture set. These pictures were fragmented and presented on the Apple Macintosh microcomputer in a picture-fragment completion task in which identification thresholds were obtained at three phases of learning: Train (initial presentation), New (initial presentation after training on a different set), and Old (repeated presentation of the Train set). Pictures were divided into five sets of two subsets of 15 pictures each, which served alternately as the Train and New sets. A total of 100 subjects participated in the task, with 10 subjects assigned to each subset. Individual thresholds for each picture at each phase of learning are presented, along with the fragmented pictures identified by 35% of the subjects across the Train and New learning phases. This set of fragmented pictures is provided for use in experiments in which a single level of fragmented image is presented for identification after a priming phase. Correlations between the Snodgrass and Vanderwart norms and identification thresholds at the three phases of learning are also reported.

Discrimination, Psychological↗
PubMed1987

Double blind controlled trials of cholecystokinin octapeptide in neuroleptic-refractory schizophrenia.

A group of 14 schizophrenics who remained symptomatic after neuroleptic treatment received either 0.02 mcg/kg CCK-8 or saline placebo intravenously. Thereafter, 13 received the alternative infusion as a crossover treatment. A second group of 16 such patients received 0.04 mcg/kg CCK-8 or saline intravenously and, thereafter, 14 of these received the alternative infusion as a crossover treatment. Psychopathology was rated prior to, 2-3 h post, and on days 3, 5 and 7 after each infusion. Ratings consisted of the BPRS, the Abrams and Taylor Scale for Emotional Blunting, the Hamilton Anxiety Scale and a Schneiderian "Positive" symptom scale abstracted from the President State Examination. Parallel groups and cross over design analyses failed to show efficacy for CCK-8.

Antipsychotic Agents↗