Low-dose oral lorazepam administration in Alzheimer subjects and age-matched controls.

Ten patients with Alzheimer's disease and ten age-matched normal controls were studied in a double-blind, placebo-controlled acute trial of 1 mg PO lorazepam to test the effects of low-dose benzodiazepine on memory and behavior in a mostly older population. Cognitive effects differed somewhat between Alzheimer patients and normal controls, with Alzheimer patients revealing predominantly "attentional" impairments and age-matched controls showing possible "disinhibition." Specifically, Alzheimer patients made more omission errors on a continuous performance task, whereas controls made more commission and intrusion errors with lorazepam versus placebo.

Differential responsivity of mood, behavior, and cognition to cholinergic agents in elderly neuropsychiatric populations.

To evaluate the possible differential responsivity of Alzheimer patients to cholinergic agents, a series of pharmacologic challenge studies in 83 neuropsychiatric patients and controls were performed contrasting a cholinergic antagonist (scopolamine) with two cholinergic agonists (arecoline and nicotine). Alzheimer patients displayed significantly greater behavioral and cognitive responses to central cholinergic blockade at lower scopolamine doses than age-matched controls or elderly depressives. These differential changes could not be explained by group differences in the sedative, physiologic, or pharmacokinetic effects of the drug.

The effects of acute scopolamine in geriatric depression.

In an intensive multidrug, multidose study, nine elderly depressed patients were administered 0.1, 0.25, and 0.

Multiple-dose arecoline infusions in Alzheimer's disease.

Twelve patients with dementia of the Alzheimer type received two-hour infusions of placebo and the muscarinic cholinergic agonist arecoline hydrobromide at rates of 1, 2, and 4 mg/h in a double-blind, randomized fashion. These infusions resulted in dose-dependent physiologic and neuroendocrine effects consistent with central cholinergic stimulation. Infusions were generally well tolerated.

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.

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).

Carbamazepine treatment of agitation associated with dementia.

Two patients with severe dementia and multiple medical problems but with no other psychiatric diagnoses were treated with carbamazepine for agitation. They tolerated the medication well and their behavior improved, consistent with carbamazepine's efficacy for agitation in other syndromes. Theoretical and practical implications are discussed.

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.

Intravenous nicotine in Alzheimer's disease: a pilot study.

In the first study to examine direct nicotinic augmentation of central cholinergic functioning in Alzheimer's disease, six patients were studied in an intensive pilot study with three doses (0.125, 0.25, and 0.

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.

Function of the adrenal cortex in patients with major depression.

Failure to suppress cortisol secretion after administration of dexamethasone occurs in up to 50% of depressed patients. To test whether this hypothalamic-pituitary-adrenal (HPA) overactivity is associated with adrenocortical hyperresponsiveness, we performed dexamethasone suppression tests (DSTs) and adrenocorticotropic hormone (ACTH) stimulation tests in depressed subjects and subjects with other psychiatric disorders. Three groups were defined: depressed nonsuppressors, depressed suppressors, and other suppressors.

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.

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.

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.

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.

A psychobiologic analysis of cognitive failures. Structure and mechanisms.

Impairments in memory, learning, and related cognitive functions can vary in most psychiatric or neuropsychiatric disorders. Although many methods have been used to measure the presence and severity of cognitive symptoms, little progress has been made in defining and contrasting possible determinants of cognitive dysfunction. We propose a theoretical framework that describes impairments of higher mental functions in terms of both "extrinsic" noncognitive processes and "intrinsic" cognitive processes.

Naloxone and Alzheimer's disease. Cognitive and behavioral effects of a range of doses.

There have been conflicting reports on the effects of naloxone hydrochloride in patients with dementia of the Alzheimer type (DAT). In addition, none of the naloxone studies in DAT used doses of 2.0 mg/kg or more, the amount necessary to produce reliable cognitive and behavioral changes in young normal subjects.

Rapid antidepressant effect of addition of lithium to tranylcypromine.

A chronically depressed patient who had not responded to treatment with several tricyclic antidepressants and monoamine oxidase inhibitors alone, responded within hours following the addition of lithium to ongoing tranylcypromine treatment in a double-blind medication trial. The findings are discussed in the context of reports of lithium augmentation of other antidepressants.

Pharmacologic modelling of Alzheimer's disease.

Evidence pointing to the central role of the cholinergic system in normal human memory function and disorders such as Alzheimer's disease has grown tremendously in recent years. Anticholinergic and non-cholinergic agents have been found to create transient memory impairments in young adults which mimic the changes associated with normal aging or amnesia. The rationale for using scopolamine, a centrally active anticholinergic agent, as a pharmacologic probe of memory function is reviewed using data from studies in animals and humans.