Low- and high-dose naloxone in dementia of the Alzheimer type.
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Adult↗
Biomedical subjects
H Weingartner
Publications and source records attributed to H Weingartner.
Central nervous system catecholamine metabolism in Korsakoff's psychosis.
We attempted to replicate previous reports of impaired central noradrenergic activity in patients with Korsakoff's psychosis. No differences were demonstrated in lumbar cerebrospinal fluid concentrations of norepinephrine or its major metabolite, 3-methoxy-4-hydroxyphenyl glycol (MHPG), or in the contribution of plasma to cerebrospinal fluid free MHPG in 6 patients with clinically well characterized Korsakoff's psychosis and 8 age-matched healthy, normal volunteers. Likewise, cerebrospinal fluid concentrations of the major metabolites of dopamine (homovanillic acid) and serotonin (5-hydroxyindoleacetic acid) were the same in patients and controls.
Aged↗
Catecholamine metabolism during clonidine withdrawal.
Abrupt cessation of clonidine treatment in hypertensive patients may precipitate a withdrawal syndrome. Since this drug is likely to be more widely prescribed to normotensive patients with neuropsychiatric diseases, we studied neurochemical, cardiovascular, and behavioral changes upon placebo substitution in seven patients receiving clonidine (6 micrograms/kg/day for 3 weeks) for treatment of alcohol amnestic disorder. Urinary excretion of all major catecholamine metabolites returned to pretreatment levels 3-5 days after discontinuing clonidine, without significant overshoot. The percentage increase during clonidine withdrawal of the norepinephrine metabolite normetanephrine was greater than were those of vanillylmandelic acid, 3-methoxy-4-hydroxyphenylglycol (MHPG), or the epinephrine metabolite metanephrine. Excretion of the dopamine metabolites homovanillic acid and 3-methoxytyramine did not change. Total plasma MHPG, heart rate, and mean arterial pressure were significantly elevated above pretreatment values 72 h after the last dose of clonidine. There was an enhancement of episodic memory compared to predrug values but no other behavioral changes were noted during clonidine withdrawal. These findings are consistent with augmented catecholamine release and central noradrenergic activation which may produce psychopathology in some psychiatric patients during clonidine withdrawal.
Aged↗
The experience of insomnia and daytime and nighttime functioning.
Ten insomniacs and matched control subjects, in whom major physiologic disorders such as sleep apnea and nocturnal myoclonus were ruled out, underwent studies of sleep, temperature, motor activity, cognitive performance, and perception of depth of sleep. Subjective descriptions of sleep differed significantly between insomniacs and normals on a variety of variables. In contrast, polysomnographic evaluation showed increased intermittent waking time and decreased sleep efficiency, and only a tendency toward decreased total sleep and increased sleep latency. Minnesota Multiphasic Personality Inventory (MMPI) evaluation revealed that insomniacs had higher scores on the F, D, and SI scales, and lower values on the K scale. On cognitive testing, insomniacs did well on tests of episodic (recent) memory, but displayed major deficits in accessing semantic memory (retrieval of material already known). Compared to normals, insomniacs described rapid eye movement (REM) sleep as relatively "light" sleep.
Adult↗
Cognitive impairments in Parkinson's disease: distinguishing between effort-demanding and automatic cognitive processes.
The study was designed to define some of the elements of cognitive impairments evident in unmedicated Parkinson's disease (PD) patients. Unlike patients with progressive dementias such as Alzheimer's disease, untreated, mildly to moderately affected PD patients are efficient at accessing previously acquired knowledge. They also can learn and remember information that can be processed "automatically," using operations requiring little cognitive capacity. However, PD patients demonstrate relatively specific cognitive impairments for effort-demanding processes. These findings are clinically useful, but also help define the boundaries of psychobiologically distinct cognitive (memory-learning) processes.
Aged↗
The Genain Quadruplets: psychological studies.
A series of behavioral studies is reported on the Genain Quadruplets. These monozygous women, all of whom have suffered or are suffering from schizophrenia, were studied previously at the National Institute of Mental Health (1955-1958) and were the subject of an extensive report by Rosenthal (1963). Although the Genains are genetically identical, the expression of the schizophrenic disorder is unequal among the quads, and this circumstance has led to speculation about the relative contributions of nature and nurture (or diathesis and stress in Rosenthal's terminology) in the development of this disease. Two goals were pursued in this investigation: one concerned a comparison of the status of the Genains in 1981 as compared with 1958; the other concerned whether data from the armamentarium of newer behavioral and neurobiological techniques invented and employed since 1958 might shed some light on the unequal expression of schizophrenia among the quadruplets. We conclude that the Genains are functioning about as well as they ever have in their adult lives, and scores on attentional tests show improvement as compared to 1958 measures. This is probably attributable to the medication (primarily neuroleptics) and other supportive treatments they have received over the years. With respect to the varying degrees of illness seen in the Genains, scrutiny of the biochemical, physiological, neuroradiological, immunogenetic, and behavioral test data leads to speculation that certain unique biochemical findings interacting with differing types and amounts of cerebral pathology constitute a major cause of the variable expression of the schizophrenic diathesis.
Antipsychotic Agents↗
The effects of desmethylimipramine on cognitive function in healthy subjects.
The cognitive effects of the specific norepinephrine (NE) uptake inhibitor desmethylimipramine (DMI) were examined in normal subjects. Although there were no differences in performance on drug compared to placebo treatment, there was an improvement in cognition 1 week after the drug had been discontinued. On DMI, there was evidence for increased noradrenergic activity, which was uncorrelated with measures of learning and memory. An improvement in mood during drug withdrawal was uncorrelated with the cognitive enhancement. It was concluded that the discontinuation of DMI, a drug which primarily affects NE uptake, improves several measures of learning and memory. Drug effects on cognition may be most pronounced during the withdrawal period.
Adult↗
Effortful and automatic memory: effects of dopamine.
With advancing age, there are changes in both cognitive functions and neurotransmitter metabolism. Dopamine plays a role in learning, memory, and related cognitive processes. We evaluated the effects of supplemental dopamine in precursor form (levodopa) on various aspects of memory in elderly normal volunteers in a controlled, double-blind study. Access to semantic memory and automatic processes were unaffected, but levodopa reliably facilitated effortful memory processing. Levodopa may be useful clinically in attenuating impairments in effortful cognitive tasks. Different neural systems probably mediate different forms of cognition.
Aged↗
Enkephalinergic-dopaminergic "reward" pathways: a critical substrate for the stimulatory, euphoric and memory-enhancing actions of alcohol--a hypothesis.
Recent evidence indicates that alcohol (ethanol) exerts specific effects on dopaminergic-enkephalinergic neuronal pathways which are involved with natural drive-induction and have also been implicated in reward and memory consolidation. It is proposed herein that the euphorigenic and "paradoxical" memory-enhancing effects of low doses of alcohol are related to its direct actions on this specific brain substrate.
Animals↗
Zimelidine effects on memory impairments produced by ethanol.
Zimelidine, a relatively specific 5-hydroxytryptamine reuptake blocker, attenuates the impairing effects of ethanol on learning and memory. The findings provide a potential basis for treatment of ethanol-related disorders and also points to the role of the serotonin system in mediating aspects of information processing in man.
Adult↗
Effects of serotonin on memory impairments produced by ethanol.
Subjects treated with low or high doses of ethanol demonstrated impaired memory, particularly in tests involving the recall of poorly learned information. Zimelidine, an inhibitor of serotonin reuptake, reversed this ethanol-induced impairment. The serotonin neurotransmitter system may mediate learning and memory in humans and may determine some of the effects of alcohol on higher mental functions.
Adult↗
Forms of memory failure.
Memory may fail in a variety of ways. Patients with Korsakoff's syndrome demonstrate global memory deficits similar to those seen in patients with early progressive dementia. Korsakoff's patients, however, may recall rules and principles for organizing information and can gain access to their previously acquired knowledge (semantic memory), whereas recent memory may be grossly impaired. In contrast, dementia patients may have little access to previously acquired knowledge and therefore have great difficulty in organizing and encoding ongoing events. These contrasting forms of memory failure have implications for understanding the structure and mechanisms of memory and learning, particularly the relationship between episodic and semantic memory, as well as the development of therapeutic strategies for cognitive impairments.
Alcohol Amnestic Disorder↗
A family with histologically confirmed Alzheimer's disease.
A Canadian family comprising 51 members affected with Alzheimer's disease was evaluated clinically, histologically, and genetically. Ancestors were traced through eight generations, and 51 members were examined at the National Institute of Mental Health, Bethesda, Md. The pedigree is consistent with autosomal dominant inheritance. The effect of interrelatedness among some parents of affected individuals is unknown. In contrast to other studies, there was not an increased incidence of Down's syndrome, hematologic malignancy, or preponderance of affected females.
Alzheimer Disease↗
Thinking disorder in depression.
This experiment demonstrated abstract reasoning deficits in depressed patients and detailed some of the components of cognition that may determine such deficits. Subjects were given a discrimination learning problem in which possible solutions had to be formulated and tested against new information. Depressed subjects performed more poorly on the task than controls. Two types of errors--inability to narrow down the set of possible solutions (poor "focusing") and perseveration on disconfirmed hypotheses--hampered the performance of depressed but not control subjects. While logic, memory, and attention were intact at an elementary level, the inability to coordinate these functions in a complex task appeared to be an important feature of the depressive impairment.
Adult↗
High-dose naloxone infusions in normals. Dose-dependent behavioral, hormonal, and physiological responses.
Hypotheses of involvement of the endogenous opioid system (EOS) in the regulation of human behavior suggest that functional blockade of the EOS should have behavioral consequences. Clinical administration of the opiate receptor antagonist naloxone hydrochloride, however, has had little or inconsistent behavioral effects in normals. This may be attributable to the use of doses insufficient to yield a complete EOS blockade. To assess this explanation, normals were administered increasing doses of naloxone hydrochloride (0.3 to 4 mg/kg) in a single-blind design. Significant dose-dependent behavioral, hormonal, and physiological effects were found. With increasing doses of naloxone, volunteers demonstrated increasingly dysphoric affects, a deterioration of performance on memory testing, increasing systolic BP and respiratory rate, and increasing plasma cortisol and growth hormone levels. These results are consistent with the expected effects of increasing EOS blockade, and thus suggest that lower doses of naloxone used in previous clinical studies may not have been sufficient to produce a complete EOS blockade. Specifically, they suggest involvement of the EOS in the tonic regulation of normal human mood, memory, BP, respirations, and plasma growth hormone and cortisol levels.
Adult↗
Neurohypophyseal hormones and cognition.
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Animals↗
High-dose naloxone affects task performance in normal subjects.
Increasing intravenous doses of naloxone (0.3 mg/kg, 1 mg/kg, and 2 mg/kg) were administered to normal subjects. Naloxone at 2 mg/kg, but not at lower doses, impaired aspects of memory as measured by a verbal learning task which assessed the direct free recall and recognition of presented versus non-presented words of a single category (effortful processing) and the monitoring of the frequency of such presentations (automatic processing). At the same time "working" memory was left unaffected. The results suggest a role for the opioid system in some memory processes in man.
Adult↗
Processing of emotional properties of stimuli by depressed and normal subjects.
This study investigated whether depressed subjects differ from controls in their ability to appreciate emotional aspects of verbal material, or in their use of emotional qualities of stimuli in learning and remembering. When asked to rate the degree of emotionality of words, depressed subjects did so essentially identically with controls. However, despite apparently similar evaluatory processing, the depressed failed to remember as well as controls. Depressed subjects were more dependent than controls on both high emotionality and high stimulus concreteness for recognition memory, but were less benefited by these properties in free recall. While providing no evidence for deficits specific to emotionality, our results suggest that relatively shallow processing of semantic aspects of stimuli may be an important factor in the memory impairment of depression.
Adult↗