Cognitive and behavioral sensitivity to scopolamine in Alzheimer patients and controls.
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Adult↗
Biomedical subjects
T Sunderland
Publications and source records attributed to T Sunderland.
Low- and high-dose naloxone in dementia of the Alzheimer type.
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Adult↗
Monoamine oxidase-inhibiting antidepressants. A clinical update.
This article outlines the latest information on the clinical efficacy of MAOIs and provides the physician with guidelines for their safe use. The important side effects of this class of drugs are also summarized along with an up-to-date account of their possible molecular mechanism of action.
Antidepressive Agents, Tricyclic↗
High dose naloxone in depression.
The behavioral effects of a 2 mg/kg iv bolus infusion of naloxone were compared with a placebo infusion using a double-blind design in a small group of inpatient depressives (n = 6) and normals (n = 8). Naloxone produced consistent and significant worsening in the rated signs and subjective symptoms of depression in the patients. In the normals, lesser changes in Hamilton depression and BPRS total scores were observed while none of the subjective scales were significantly altered. The data suggest that depressives manifest a more marked and subjectively more intense response to naloxone compared to normals. Further studies are required to confirm this preliminary finding and to clarify its relationship to the pathogenesis of depression.
Adult↗
Amoxapine and neuroleptic side effects: a case report.
A depressed patient developed neuroleptic-like side effects while being treated with amoxapine alone. Elevation of her plasma prolactin level and significant ex vivo neuroleptic activity were found despite therapeutic amoxapine levels.
Amoxapine↗
Increased cognitive sensitivity to scopolamine with age and a perspective on the scopolamine model.
18 older normal volunteers (mean age = 66.5 +/- 7.9 years) and 46 younger volunteers (mean age = 27.0 +/- 6.1 years) were administered the anticholinergic drug scopolamine (0.5 mg i.v.) followed by a battery of cognitive tests evaluating attention, learning and memory. The older subjects were significantly more impaired than the younger by scopolamine on some tests of learning and memory. This increased sensitivity of the older group to scopolamine is consistent with studies in animals and humans showing decreased cholinergic system function with age. The findings also indicate that age is an important variable to consider in using the scopolamine model of memory impairment. The cognitive impairment caused by scopolamine in younger subjects in this and prior studies is similar to some, but not all aspects of the impairment which occurs in normal aging. Scopolamine also caused impairments on digit span and word fluency tasks, which are not consistent with normal aging changes. In the older group of subjects, scopolamine produced aspects of the cognitive impairment which occurs in AD on tests of episodic memory and learning, vigilance-attention, category retrieval, digit span, and number of intrusions. Other areas of cognition that are of relevance to aging and AD such as psychomotor speed, praxis, concept formation and remote memory were not evaluated in this study. Some of these are being evaluated in ongoing studies, along with additional and more specific tests of retrieval from knowledge memory, implicit memory and attention. The scopolamine model has provided a fruitful pharmacologic starting point for the study of a number of cognitive operations. The idea of dissecting apart aspects of memory systems pharmacologically depends on the availability of neurochemically specific drugs and on the specificity and sensitivity of neuropsychological tests for distinct cognitive operations or domains. Further studies using such tools will aid not only in the understanding of the impairments which occur in aging and in AD, but also of the conceptualization of memory and other cognitive operations and ultimately the physiological mechanisms involved in memory and learning.
Acetylcholine↗
Protein alterations in olfactory neuroblasts from Alzheimer donors.
Definitive diagnosis of Alzheimer's disease (AD) is made by pathologic examination of postmortem brain tissue in conjunction with a clinical history of dementia. To date, there are no good biological markers for a positive diagnosis of AD in the living patient. In an effort to identify biological markers useful both in the clinical and pathologic diagnosis of AD, we have investigated disease-specific protein alterations in cultured olfactory neurons. Olfactory neurons are readily accessible by biopsy, can be propagated in primary cell culture as olfactory neuroblasts (ONs), and exhibit several elements of AD brain pathophysiology making them powerful tools for the study of AD. Two-dimensional gel analysis of ON proteins from neuropsychologically evaluated AD donors revealed a set of five proteins (Mr 17-50 kD, pI 4.8-6.7) that were significantly altered in concentration when compared to cells from age-matched controls. Further characterization and microsequence analysis could lead to the identification of proteins that may have important diagnostic or therapeutic value in the treatment of AD.
Aged↗
Alzheimer's disease. How memory fails: a theoretical model.
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Aged↗
Interactions of prefrontal cortex during eyeblink conditioning as a function of age.
Changes in regional cerebral blood flow (rCBF) in eleven elderly subjects during pairings of tone and air puff were compared to rCBF changes during pairings in young subjects. Although all subjects reported being aware of the relationship between tone and air puff, elderly subjects did not condition as well as young subjects and their rCBF measures were attenuated. Covarying the performance differences between young and old subjects did not change this conclusion suggesting that differences in neural activation during learning are related to binding of CS-US information prior to the impact of the association on performance. Both groups showed learning-specific rCBF changes in cerebellum, inferior right prefrontal cortex and posterior cingulate. However, only in young subjects were there learning-specific changes in rCBF in left temporal cortex, midbrain, caudate, and inferior left prefrontal cortex. Analysis of learning-dependent patterns of functional connectivity of inferior left prefrontal cortex showed only young subjects had a strong left prefrontal functional connectivity with cerebellum, hippocampus, thalamus and temporal cortex. Thus, beyond changes in regional activity, these data also suggest that age may alter the operations of functional networks underlying learning and memory.
Adolescent↗
Depression through the ages.
This commentary praises the authors' substantial achievement in their review of the controversial area of biological modeling in depression. While definitive conclusions are as of yet impractical, particularly in reference to the multifaceted but largely uncharted relationship between aging and depression, students of the field will be well served to have this review as one of their starting points.
Aged↗
Psychobiological modeling of age-related memory changes.
Useful models of age-related human and animal memory changes should simulate specific features of cognitive impairment associated with aging. It is necessary but not sufficient to demonstrate that manipulations such as those produced by lesions and drugs cause impairments in some cognitive function such as memory. A useful model should be able to reproduce a pattern of cognitive changes in which islands of spared versus impaired functioning resemble those associated with aging and differ from those produced by other conditions. This requires the use of research strategies utilizing multivariate treatment and dependent measure designs. The papers in this section illustrate the value of such a research approach.
Aging↗
Geriatric psychopharmacology: why does age matter?
Older adults respond less predictably than younger adults to most medications, typically requiring lower daily doses to achieve desired therapeutic effects and minimize adverse effects and toxicity. This unpredictability is particularly evident among the frail elderly, who are at the upper extreme of the life cycle and often suffer from central neurodegenerative disorders and/or a significant burden of comorbid medical problems. Yet this population has a burgeoning need for clinical services and in recent years has become an increasingly important focus of attention among practitioners. The goal of this review is to provide clinicians with a conceptual framework for understanding and responding to aging and age-related events that influence pharmacotherapeutics in older patients with behavioral disorders. Limitations and gaps in our knowledge base are also highlighted. The article includes a phenomenological overview of the aging process, a consideration of age-related factors that influence the pharmacokinetic and pharmacodynamic properties of psychotropic drugs, and suggested methods of enhancing medication compliance.
Aged↗
Diagnosis and treatment of Alzheimer disease and related disorders. Consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer's Association, and the American Geriatrics Society.
OBJECTIVE: A consensus conference on the diagnosis and treatment of Alzheimer disease (AD) and related disorders was organized by the American Association for Geriatric Psychiatry, the Alzheimer's Association, and the American Geriatrics Society on January 4 and 5, 1997. The target audience was primary care physicians, and the following questions were addressed: (1) How prevalent is AD and what are its risk factors? What is its impact on society? (2) What are the different forms of dementia and how can they be recognized? (3) What constitutes safe and effective treatment for AD? What are the indications and contraindications for specific treatments? (4) What management strategies are available to the primary care practitioner? (5) What are the available medical specialty and community resources? (6) What are the important policy issues and how can policymakers improve access to care for dementia patients? (7) What are the most promising questions for future research? PARTICIPANTS: Consensus panel members and expert presenters were drawn from psychiatry, neurology, geriatrics, primary care, psychology, nursing, social work, occupational therapy, epidemiology, and public health and policy. EVIDENCE: The expert presenters summarized data from the world scientific literature on the questions posed to the panel. CONSENSUS PROCESS: The panelists listened to the experts' presentations, reviewed their background papers, and then provided responses to the questions based on these materials. The panel chairs prepared the initial drafts of the consensus statement, and these drafts were read by all panelists and edited until consensus was reached. CONCLUSIONS: Alzheimer disease is the most common disorder causing cognitive decline in old age and exacts a substantial cost on society. Although the diagnosis of AD is often missed or delayed, it is primarily one of inclusion, not exclusion, and usually can be made using standardized clinical criteria. Most cases can be diagnosed and managed in primary care settings, yet some patients with atypical presentations, severe impairment, or complex comorbidity benefit from specialist referral. Alzheimer disease is progressive and irreversible, but pharmacologic therapies for cognitive impairment and nonpharmacologic and pharmacologic treatments for the behavioral problems associated with dementia can enhance quality of life. Psychotherapeutic intervention with family members is often indicated, as nearly half of all caregivers become depressed. Health care delivery to these patients is fragmented and inadequate, and changes in disease management models are adding stresses to the system. New approaches are needed to ensure patients' access to essential resources, and future research should aim to improve diagnostic and therapeutic effectiveness.
Alzheimer Disease↗