Handbook of Psychopharmacology: Volume 20 Psychopharmacology of the Aging Nervous System

ISBN-13: 9781461282525 / Angielski / Miękka / 2011 / 500 str.

Leslie L. Iversen; Susan D. Iversen; Solomon Snyder

Opis

"Psychopharmacology of the Aging Nervous System" was selected as the topic for Volume 20 of the Handbook of PsychopharmacoloffY. Senile dementia is now widely recognized as a medical and social problem likely to reach epidemic proportions by the turn of the century. By that time it is esti mated that almost 20% of the population in most developed countries will be over the age of 65 and at a conservative estimate 1 in 10 of them will suffer from a dementing illness. Many symposia have appeared over the last few years describing the neuropathological and neurochemical deficiencies in Alzheimer's and other forms of dementia, the neuropsychological features of the disease, and attempts to treat it. In this volume, we have selected topics and authors who are beginning to question some of the earlier assumptions and to ask different questions about dementia. In the first four chapters the neuropathology and neu rochemistry of dementia are reevaluated. It is important to understand the relationship between the formation of amyloid plaques and neurofibrillary tangles, the progressive degeneration in cortex, and the neurochemical deafferentation of cortex. In particular, the possibility is considered that the most severe pathology is seen in a well-defined limbo/cortical circuitry known to be involved in mnemonic processing. The growing interest in the genetic determinants of familial Alz heimer's is reviewed. It is also recognized that detailed comparisons of the neural and psychological characteristics of the various degenerative dis eases that impair cognitive processing may be valuable."

Spis treści

1 Neuropathological and Neurochemical Aspects of Alzheimer’s Disease.- 1. Introduction.- 2. The Neuropathology of Alzheimer’s Disease.- 2.1. The Gross Changes of Alzheimer’s Disease.- 2.2. Nerve Cell Loss in Alzheimer’s Disease.- 2.3. Degenerative Changes in Nerve Cells in Alzheimer’s Disease.- 2.4. The Senile Plaque.- 2.5. The Neurofibrillary Tangle.- 2.6. Granulovacuolar Degeneration.- 2.7. The Hirano Body.- 2.8. Lewy Bodies and Alzheimer’s Disease.- 2.9. Changes in Glial Cells.- 2.10. Changes in Blood Vessels.- 2.11. The Relationship between Senile Plaques, Neurofibrillary Tangles, and Cerebrovascular Amyloid.- 3. Alzheimer-Type Changes in Conditions Other than Alzheimer’s Disease.- 3.1. Nondemented Individuals of All Ages.- 3.2. Down’s Syndrome at Middle Age.- 3.3. Parkinson’s Disease.- 3.4. Boxer’s Encephalopathy and Other Conditions.- 4. Alzheimer’s Disease and Patient Age.- 5. Biochemical Correlates of Pathological Changes.- 5.1. Neurotransmitter Changes.- 5.2. Changes in Protein Synthesis.- 6. Relationship between Plaques and Tangles and Nerve Cell Atrophy and Loss.- 7. Relationship between Extent of Pathological Changes and Degree of Dementia.- 7.1. Gross and Light Microscopic Relationships.- 7.2. Relationships to Dementia at Ultrastructural Level.- 8. Pathogenetic Considerations.- 8.1. Where Is the Site of the Primary Lesion in Alzheimer’s Disease? Is It in the Cerebral Cortex or in the Subcortex?.- 8.2. Is the SP or the NFT the Site of Primary Damage to Nerve Cells in Alzheimer’s Disease?.- 8.3. How Are SP Formed?.- 8.4. Where Does the Process of Alzheimer’s Disease Begin?.- 9. Concluding Remarks.- 10. References.- 2 Basal Forebrain Cholinergic Neurons and Alzheimer’s Disease.- 1. Introduction.- 2. Basal Forebrain Cholinergic Systems.- 3. Cholinergic Alterations in AD.- 3.1. Cortex.- 3.2. Basal Forebrain.- 3.3. Cerebral Spinal Fluid AChE and Other Peripheral Changes.- 4. Cholinergic Physiology.- 4.1. Behavioral Experiments.- 4.2. Electrophysiological Studies.- 4.3. Transsynaptic Consequences of Basal Forebrain Cholinergic Lesions in Experimental Animals.- 4.4. Cholinergic Pharmacotherapy in AD.- 5. Conclusion.- 6. References.- 3 Neurochemical Studies in Dementia.- 1. Introduction.- 1.1. Definition of Dementia.- 1.2. Methodology of Human Neurochemistry.- 2. Alzheimer’s Disease.- 2.1. Acetylcholine.- 2.2. Correlations of Cholinergic Deficit with Cognitive Impairment.- 2.3. Norepinephrine and Dopamine.- 2.4. Serotonin.- 2.5. Amino Acids.- 2.6. Neuropeptides.- 3. Other Cortical Dementias.- 4. Subcortical Dementias.- 4.1. Parkinson’s Disease and Progressive Supranuclear Palsy.- 4.2. Huntington’s Disease.- 4.3. Depression.- 5. Alcohol Dementia.- 6. Confusional States.- 7. Summary.- 8. References.- 4 Chemical Neuroanatomy of Alzheimer’s Disease.- 1. Introduction: Relationship of Neural Connections and Neurotransmitters with Alzheimer Pathology.- 2. Limbic and Cortical Connections and Neurotransmitters in Alzheimer’s Disease.- 2.1. Distribution of Lesions in the Hippocampal Formation.- 2.2. Distribution of Lesions in the Amygdala.- 2.3. Distribution of Neocortical Lesions.- 2.4. Neurotransmitters in Affected Limbic and Corticocortical Connections.- 3. Brain Stem and Basal Forebrain-Cortical Connections and Neurotransmitters in Alzheimer’s Disease.- 3.1. Magnocellular Basal Nucleus.- 3.2. Thalamic Intralaminar Nuclei.- 3.3. Hypothalamus.- 3.4. Brain Stem Monoamine Cell Groups.- 3.5. Brain Stem Cholinergic Cell Groups.- 4. Implications for the Pathogenesis and Treatment of Alzheimer’s Disease.- 5. References.- 5 Dementia in Parkinson’s Disease.- 1. Introduction.- 2. Brain Lesions in Patients with Parkinson’s Disease.- 3. Dementia and Lesions.- 3.1. Neuropathology.- 3.2. Neurochemistry.- 4. Parkinsonian Dementia.- 4.1. Prevalence.- 4.2. Characteristics of Parkinsonian Psychopathology.- 5. Symptoms and Lesions.- 5.1. Dopamine-Dependent Symptoms?.- 5.2. Norepinephrine-Dependent Symptoms?.- 5.3. Serotonin-Dependent Symptoms?.- 5.4. Acetylcholine-Dependent Symptoms?.- 5.5. Somatostatin-Dependent Symptoms?.- 6. Conclusion.- 7. References.- 6 Alzheimer’s Disease: Genetic Theories of Etiology.- 1. Introduction.- 2. The Genetic Hypothesis.- 2.1. Pedigree Studies of Presenile Disease.- 2.2. Studies of Pooled Proband Relatives.- 3. Critical Methodological Issues.- 3.1. Diagnostic Heterogeneity.- 3.2. Age-Dependent Onset.- 3.3. Resulting Ambiguity in Classical Twin and Linkage Studies.- 4. Predicted Characteristics of Genetically Caused AD.- 4.1. Gene Expression May Be Described by a Probability Distribution.- 4.2. Expected Familial Incidence in a Rare Dominant Disorder.- 4.3. Expected Familial Incidence When a Dominant Predisposing Gene Is Common.- 4.4. Effect of Gene Frequency on Relative Risks for Proband versus Control Relatives.- 4.5. Effects of Phenocopies in the Index Case Series.- 5. Review of Previous Studies.- 5.1. Approach.- 5.2. Studies before 1955.- 5.3. Studies after 1955.- 6. Current Studies.- 6.1. The Minnesota State Hospital Studies.- 6.2. The Duke Collaborative Studies.- 6.3. The Baltimore Nursing Home Study.- 6.4. The New York Studies.- 6.5. Autosomal Dominant Inheritance Suggested by Both the Baltimore and New York Studies.- 7. Implications and Strategies for Future Research.- 7.1. Status of the Genetic Hypothesis.- 7.2. Implications of Age-Dependent Expression of AD.- 7.3. Additional Research Strategies.- 8. References.- 7 The Cholinergic Hypothesis of Memory: A Review of Animal Experiments.- 1. Introduction.- 2. Conceptual Issues.- 3. Methodological Issues.- 4. Anatomy of Forebrain Cholinergic Pathways.- 5. Pharmacology of Central Cholinergic Neurons.- 6. Pharmacological Evidence for Cholinergic Involvement in Sensory, Attentional, and Motor Functions.- 7. Pharmacological Studies of Rodent Learning and Memory.- 7.1. Discrimination Learning.- 7.2. Avoidance Learning.- 7.3. Spontaneous and Rewarded Alternation Behavior.- 7.4. Maze Learning.- 7.5. Intracerebral Injections.- 8. Lesion Studies.- 8.1. Lesions of Ascending Cholinergic Projections.- 8.2. Recovery of Function after Lesions.- 8.3. Tissue Transplants.- 9. Pharmacological Studies of Primate Memory.- 9.1. Delayed Matching to Sample.- 9.2. Primate Studies: Delayed Responding.- 9.3. Other Behavioral Tasks.- 9.4. Primate Studies: Conclusions.- 10. Summary and Concluding Remarks.- 11. References.- 8 Behavioral Models of Aging in Nonhuman Primates.- 1. Introduction.- 2. Some Characteristics of Age-Related Behavioral Deficits in Nonhuman Primates.- 2.1. Behavioral Test Paradigms.- 2.2. Recent Memory Impairment.- 2.3. Hypersensitivity to Visual Interference.- 2.4. Discrimination Learning.- 2.5. Impairment in Reversal Learning.- 2.6. Synopsis.- 3. Relationship of Age-Related Behavioral Deficits in Nonhuman Primates to Humans.- 3.1. Impairments in Recent Memory.- 3.2. Hypersensitivity to Interfering Stimuli.- 3.3. Increased Perseveration/Behavioral Rigidity.- 3.4. Development of Human Memory Tests Based on Nonhuman Primate Tasks.- 4. Relationship of Age-Related Behavioral Deficits in Nonhuman Primates to Rodents.- 4.1. Recent Memory.- 4.2. Hypersensitivity to Interference.- 4.3. Increased Perseveration/Behavioral Rigidity.- 4.4. Summary.- 5. Possible Insights from Comparisons with Nonhuman Primates Given Discrete Brain Lesions.- 5.1. Frontal Cortex Lesions.- 5.2. Nucleus Basalis of Meynert Lesions.- 5.3. Hippocampal Lesions.- 5.4. Amygdala Lesions.- 5.5. Combined Lesions of Different Brain Regions.- 5.6. Summary.- 6. Possible Insights from Drugs That Impair Performance on Memory Tasks in Young Subjects.- 6.1. Scopolamine and Other Anticholinergics.- 6.2. Diazepam and Benzodiazepines.- 6.3. Tetrahydrocannabinol.- 7. Drugs for Improving Age-Related Cognitive Losses: Current Status and Future Prospects.- 7.1. Neurotransmitter Modulation.- 7.2. Nootropics.- 7.3. Neuropeptides.- 8. Synthesis and Discussion.- 9. References.- 9 Cholinergic Drugs and Human Cognitive Performance.- 1. Introduction.- 2. The Effects of Cholinergic Agents on Processes Involved in Learning and Memory in Experimental Animals.- 3. The Effects of Cholinergic Agents on Processes Involved in Learning and Memory in Young Adult Human Subjects.- 4. Clinical Trials of Cholinergic Agents in Patients with Dementia of the Alzheimer Type or Aged Volunteers.- 5. Implications and New Directions.- 6. References.- 10 Treatment of Dementia with Vasoactive Drugs.- 1. Background and Rationale.- 1.1. Multiinfarct Dementia.- 1.2. Degenerative Dementias.- 2. Traditional Vasodilators.- 3. Recent Developments and Future Prospects.- 3.1. Calcium Channel Blockers.- 3.2. Excitatory Amino Acid Antagonists.- 4. References.- 11 New Pharmacological Perspectives on Nootropic Drugs.- 1. Introduction.- 2. Known Compounds.- 3. Goals of This Chapter.- 4. Distribution of Drugs in Brain.- 5. Neuropsychopharmacological Studies.- 5.1. Aged Rat Quantitative EEG.- 5.2. Therapeutic Window Discovered in Quantitative EEG Studies.- 5.3. Effects on New Learning and the Therapeutic Window.- 5.4. Effects on Firing Rate of Neurons of the Medial Septal Nucleus and the Area Ventral to the Globus Pallidus.- 5.5. Therapeutic Window Shown in Single-Neuron Firing Rate.- 5.6. Cerebral Intraventricular Administration of Pramiracetam and Piracetam and Effects on Single-Neuron Firing Rates.- 5.7. Functional Hippocampal Lesions and the Therapeutic Window.- 6. Neurochemical Studies.- 7. Relationship to Endogenous Substances.- 8. Nootropic Drugs and Arguments for Supplementary Choline.- 9. Clues to the Mode of Action of Nootropic Drugs.- 10. Some Thoughts on Clinical Trials.- 11. Summary and Conclusion.- 12. References.