The study of neural aging is a central topic in neuroscience, neuropsychology and gerontology. Some well-known age-related neurological diseases include Parkinson's and Alzheimer's, but even more common are problems of aging which are not due to disease but to more subtle impairments in neurobiological systems, including impairments in vision, memory loss, muscle weakening, and loss of reproductive functions, changes in body weight, and sleeplessness. As the average age of our society increases, diseases of aging become more common and conditions associated with aging need more attention by doctors and researchers.
This book offers an overview of topics related to neurobiological impairments which are related to the aging brain and nervous system. Coverage ranges from animal models to human imaging, fundamentals of age-related neural changes and pathological neurodegeneration, and offers an overview of structural and functional changes at the molecular, systems, and cognitive levels. Key pathologies such as memory disorders, Alzheimer's, dementia, Down syndrome, Parkinson's, and stroke are discussed, as are cutting edge interventions such as cell replacement therapy and deep brain stimulation. There is no other current single-volume reference with such a comprehensive coverage and depth.
Authors selected are the internationally renowned experts for the particular topics on which they write, and the volume is richly illustrated with over 100 color figures. A collection of articles reviewing our fundamental knowledge of neural aging, the book provides an essential, affordable reference for scientists in all areas of Neuroscience, Neuropsychology and Gerontology.
* The most comprehensive source of up-to-date data on the neurobiology of aging, review articles cover: normal, sensory and cognitive aging, neuroendocrine, structural and molecular factors, and fully address both patholgy and intervention
* Chapters represent an authoritative selection of relevant material from the most comprehensive source of information about neuroscience ever assembled, (Encyclopedia of Neuroscience), synthesizing information otherwise
dispersed across a number of journal articles and book chapters, and saving researchers the time consuming process of finding and integrating this information themselves
* Offering outstanding scholarship, each chapter is written by an expert in the topic area and over 20% of chapters feature international contributors, (representing 11 countries)
* Provides more fully vetted expert knowledge than any existing work with broad appeal for the US, UK and Europe, accurately crediting the contributions to research in those regions
* Fully explores various pathologies associated with the aging brain (Alzheimer's, dementia, Parkinson's, memory disorders, stroke, Down's syndrome, etc.)
* Coverage of disorders and key interventions makes the volume relevant to clinicians as well as researchers
* Heavily illustrated with over 100 color figures
A single volume of 85 articles, the Handbook of the Neurobiology of Aging is an authoritative selection of relevant chapters from the Encyclopedia of Neuroscience, the most comprehensive source of neuroscience information assembled to date (AP Oct 2008). The study of neural aging is a central topic in neuroscience, neuropsychology and gerontology. Some well-known age-related neurological diseases include Parkinson's and Alzheimer's, but even more common are problems of aging which are not due to disease but to more subtle impairments in neurobiological systems, including impairments in vision, memory loss, muscle weakening, and loss of reproductive functions, changes in body weight, and sleeplessness. As the average age of our society increases, diseases of aging become more common and conditions associated with aging need more attention by doctors and researchers. This book offers an overview of topics related to neurobiological impairments which are related to the aging brain and nervous system. Coverage ranges from animal models to human imaging, fundamentals of age-related neural changes and pathological neurodegeneration, and offers an overview of structural and functional changes at the molecular, systems, and cognitive levels. Key pathologies such as memory disorders, Alzheimer's, dementia, Down syndrome, Parkinson's, and stroke are discussed, as are cutting edge interventions such as cell replacement therapy and deep brain stimulation. There is no other current single-volume reference with such a comprehensive coverage and depth. Authors selected are the internationally renowned experts for the particular topics on which they write, and the volume is richly illustrated with over 100 color figures. A collection of articles reviewing our fundamental knowledge of neural aging, the book provides an essential, affordable reference for scientists in all areas of Neuroscience, Neuropsychology and Gerontology. The most comprehensive source of up-to-date data on the neurobiology of aging, review articles cover: normal, sensory and cognitive aging; neuroendocrine, structural and molecular factors; and fully address both patholgy and intervention Chapters represent an authoritative selection of relevant material from the most comprehensive source of information about neuroscience ever assembled, (Encyclopedia of Neuroscience), synthesizing information otherwise dispersed across a number of journal articles and book chapters, and saving researchers the time consuming process of finding and integrating this information themselves Offering outstanding scholarship, each chapter is written by an expert in the topic area and over 20% of chapters feature international contributors, (representing 11 countries) Provides more fully vetted expert knowledge than any existing work with broad appeal for the US, UK and Europe, accurately crediting the contributions to research in those regions Fully explores various pathologies associated with the aging brain (Alzheimer's, dementia, Parkinson's, memory disorders, stroke, Down's syndrome, etc.) Coverage of disorders and key interventions makes the volume relevant to clinicians as well as researchers Heavily illustrated with over 100 color figures
Handbook of the Neuroscience of Aging 4
Copyright Page 6
Table of Contents 7
Contributors 13
Preface 19
Environment versus Heredity in Normal and Pathological Aging of Neurological Functions 23
Normal versus Pathological Aging 23
Heredity versus Environment 23
Central versus Peripheral Impairments 24
Conclusions 26
Further Reading 26
Aging of the Brain 27
Possible Causal Factors 27
Structural Changes 27
Biochemical and Metabolic Changes 30
Further Reading 31
Functional Neuroimaging Studies of Aging 33
Introduction 33
Methodological Issues in Studying Aging 33
Reduced Brain Activity in Older Adults 34
Increased Brain Activity in Older Adults 36
Different Cognitive Networks in Older.Adults 37
Genetic Factors in Brain Aging 38
Conclusions 39
Further Reading 40
Aging: Extracellular Space 41
Gross Anatomic Aging Changes: Extracellular Space 41
Diffusion and Extrasynaptic Transmission 41
Measurements of the Diffusion Parameters of the ECS 41
ECS Diffusion Parameters during Aging 43
Changes in ECS Diffusion Parameters in an APP23 Mouse Model of Alzheimer's Disease 47
Concluding Remarks 48
Further Reading 48
Brain Volume: Age-Related Changes 49
Introduction 49
The Myelin Model of the Human Brain 49
Functional Implications of the.Myelin.Model 52
Brain Development during Childhood to Adolescence 53
Brain Development Continues during Adulthood until Middle Age 53
Aging and Myelin Breakdown 56
Functional Implications of Age-Related Myelin Breakdown 57
Conclusions 58
Further Reading 59
Brain Composition: Age-Related Changes 61
Lipids 61
Metals and Oxidations 62
Racemization 63
Conclusions 64
Further Reading 64
Glial Cells: Microglia during Normal Brain Aging 65
Background 65
Morphology 65
Cellular Markers 65
Distribution 65
Origin 65
Function 65
Pathology 66
Further Reading 67
Wallerian Degeneration 75
Introduction 75
Morphologic Changes during Wallerian Degeneration of Peripheral Nerve 75
Axonal Changes Following Nerve Transection 75
Schwann Cell Changes Following Nerve Transection 76
Macrophage Recruitment and Action Following Nerve Transection 77
Neuronal Regenerative Responses Following Nerve.Transection 77
Molecular Alterations Occurring during.Wallerian Degeneration of Peripheral Nerve 78
A.Comparison of Wallerian Degeneration in the PNS and CNS 79
Recent Findings Indicating that Axonal Degeneration Results from Active Self-.Destruction Rather than Simple Atrophy of Severed 80
Further Reading 81
Synaptic Plasticity: Neuronogenesis and Stem Cells in Normal Brain.Aging 83
Introduction 83
Characterization of Neural Stem Cells 83
Neurogenesis Is Decreased with Aging 84
Modulation of Neurogenesis in the.Aged.Brain 84
Implications of Decreased Neurogenesis in the Aging Brain 85
Further Reading 86
Synaptic Plasticity: Learning and Memory in Normal Aging 87
LTP/LTD and Learning and Memory 87
Learning and Memory and Aging 87
Age-Related Changes in LTP/LTD 88
Potential Cellular Mechanisms Underlying Age-Related Changes in LTP/LTD 90
Changes in NMDA Receptors 90
Changes in Calcium Regulation 90
Changes in BDNF Signaling 90
Changes in Calcineurin 90
Role of Oxygen Radicals 91
Changes in Protein Synthesis 91
Conclusions 91
Further Reading 91
Lipids and Membranes in Brain Aging 93
Introduction 93
Brain Membrane Fluidity 93
Brain Membrane Cholesterol Levels 93
Brain Membrane Phospholipids and Fatty.Acids 94
Fatty Acids of Brain Phospholipids 94
Enzymes Regulating Membrane Phospholipids 95
Phospholipase(s) A2 95
Oxidative Stress, Aging, and Membrane Phospholipids 96
Brain Lipid Domains 96
Exofacial and Cytofacial Leaflet Fluidity 97
Transbilayer Cholesterol Distribution 97
Lipid Rafts and Caveolae 98
Conclusions 98
Further Reading 99
Metal Accumulation during Aging 101
Introduction 101
Free Radicals, Transition Metals, and.OS 101
The Free Radical-Mitochondrial. Theory.of.Aging 101
Iron Deposition in the Aging CNS 102
Iron Deposition in Alzheimer's and Parkinson's Diseases 103
Iron Deposition in Other Human CNS.Disorders 103
Hypothesis 103
Glial Iron Sequestration in Brain Aging.and.Disease 103
Astrocytes 103
Iron Deposition in Subcortical Astroglia 104
Heme Oxygenase-1: Transducer of Mitochondrial Iron Deposition in 'Stressed' Astroglia 104
Heme Oxygenase 104
HO-1 and Mitochondrial Iron Sequestration 105
HO-1, Intracellular OS, and the Mitochondrial Permeability Transition 105
HO-1 Expression in Human CNS Aging and Disease 106
Normal aging 106
Alzheimer's disease 106
Parkinson's disease 106
Other disorders 106
Conclusions and Implications 106
Further Reading 108
Oxidative Damage in Neurodegeneration and Injury 109
Introduction 109
Aging and Neurodegeneration 109
Mitochondria as a Major Source of Superoxide under Normal Conditions 109
Antioxidant/Antiaging Mechanisms: Superoxide.Scavenging 109
Antioxidant/Antiaging Mechanisms: Repair of.Oxidized Residues 110
Injury and Neurodegeneration 111
Excitotoxicity 111
Inflammation 113
Apoptosis 114
Nature of Aggregated Deposits in.Neurodegenerative Diseases 115
Alzheimer's Disease 115
Parkinson's Disease 115
Polyglutamine Diseases 116
Huntington's Disease 116
Amyotrophic Lateral Sclerosis 116
Neuroprotection Strategies: Problems and Perspectives 116
Conclusions 117
Further Reading 118
Protein Folding and the Role of Chaperone Proteins in.Neurodegenerative Disease 119
Introduction 119
Protein Misfolding, Aggregation, and Molecular Chaperones 119
Protein Aggregation and Neurodegeneration 119
Molecular Chaperones and Neurodegeneration 120
Mechanisms of Chaperone-Mediated Neuroprotection 120
Molecular Chaperones as Potential Drug.Targets 121
Conclusions 122
Further Reading 122
Role of NO in Neurodegeneration 123
Introduction 123
NO in the Nervous System 123
NO Molecular Targets 124
Neurotoxic Effects of NO 125
NO and Neurodegenerative Diseases 126
Conclusion 128
Further Reading 128
Axonal Transport and Neurodegenerative Diseases 129
Introduction 129
Basic Mechanisms of Axonal Transport 129
Axonal Transport and Neurodegenerative Diseases 130
Kinesin Mutation in Hereditary Spastic Paraplegia 130
Dynactin Mutations in Distal Spinal and Bulbar.Muscular Atrophy 131
Kinesin Mutations in Charcot-Marie.-Tooth Disease 131
Axonal Transport Defects in Alzheimer's Disease.and Other Tauopathies 131
Axonal Transport and Huntington's Disease 132
Axonal Transport and Amyotrophic Lateral Sclerosis 132
Axonal Transport and Synucleinopathies 133
Conclusions and Future Directions for Research 133
Further Reading 133
Inflammation in Neurodegenerative Disease and Injury 135
Overview 135
Features of Neuroinflammation 135
Glia: Microglia and astrocytes 135
Cytokines, chemokines, and lymphokines 136
What Triggers Neuroinflammation? 136
How Does Neuroinflammation Affect Neurons? 136
Evidence for Inflammation in Neurodegenerative Diseases 136
Clinical and Epidemiological Evidence for Inflammation in PD 137
Evidence for Oxidative Stress and Inflammation in Experimental Models of PD 137
Anti-inflammatory Drugs and PD 138
Inflammation in Acute CNS Injury: Traumatic Brain Injury 138
Conclusions 139
Further Reading 140
Relevant Websites 140
Cholinergic System Imaging in the Healthy Aging Process and Alzheimer Disease 141
Introduction 141
The Cholinergic System 141
Anatomy of the Cholinergic System 141
Cholinergic Neurotransmission 142
Targeting the Cholinergic System In Vivo 145
Pet Imaging of Cholinergic Receptor Binding and ChE Activity 145
How can PET measure neuroreceptor binding and density in vivo? 145
Cholinergic Markers in PET 146
Perspective of neuroreceptor imaging in Alzheimer's disease 148
Functional Imaging of Cholinergic Treatment Effects 149
MRI Studies to Detect Atrophy of Cholinergic Nuclei 149
Imaging the Cholinergic System In Vivo: Future Perspectives 150
Further Reading 152
Programmed Cell Death 153
Introduction 153
History 153
Evolution 153
The Functions of PCD in the Nervous System 153
PCD by Autonomous versus Conditional Specification 154
Molecular Regulation of Cell Death and Survival by NTFs 154
Intracellular Regulation of Cell Death 155
Different Types of Neuronal Death 157
Pathological Neuronal Death 159
Further Reading 160
Apoptosis in Neurodegenerative Disease 161
Apoptosis 161
Molecular Regulation of Apoptosis 161
Caspases 161
Bcl-2 Family 161
Extrinsic versus Intrinsic Death Pathway 162
Apoptosis and Neurodegeneration 163
Alzheimer's Disease 163
Parkinson's Disease 164
Huntington's Disease 165
Amyotrophic Lateral Sclerosis 166
Nonapoptotic Neurodegeneration 166
Summary 167
Further Reading 167
Autonomic and Enteric Nervous System: Apoptosis and Trophic Support during Development 169
Introduction 169
Apoptotic Cells and Molecular Mechanisms 169
Apoptosis in the Nervous System and the.Discovery of Neurotrophic Factors 169
Lessons from Mutant Mice 170
Trk Receptors and Ligands Regulate Cell.Death In Vivo in the Sympathetic Nervous System 171
Ret Signaling Promotes Sympathetic Neuron Precursor Migration and Supports Axon Extension Required for Sympathetic Neurons to I 173
Programmed Cell Death in the Parasympathetic Nervous System 173
Mechanisms Governing Neuron Number in the ENS 174
Apoptosis in Neuronal Injury 175
Summary 175
Further Reading 176
Proteasome Role in Neurodegeneration 177
Introduction 177
The Proteasome 177
Neuronal Degeneration and the Proteasome 178
Synaptic Dysfunction and the Proteasome 179
Axonal Degeneration and the Proteasome 180
Conclusions 181
Further Reading 182
Genomics of Brain Aging: Nuclear and Mitochondrial Genomes 183
Introduction 183
Gene Expression Profiles of the Aging Brain 183
Trends in Animal Models 184
Trends in Humans 186
Mitochondrial Mutations and Aging 186
Genomic Effects of Mitochondrial Mutations 188
Conclusion 189
Further Reading 189
Relevant Websites 189
Gene Expression in Normal Aging Brain 191
Introduction 191
Minimal Neuron Loss with Age 191
Gene Alleles: Single Nucleotide Polymorphisms 191
Gene Expression 191
Brain Aging across Species 193
Brain Aging and Insulin-Like Growth Factor 193
Regulation of Gene Expression 194
Attenuation of Brain Aging 194
Brain Aging and AD 194
Technologic Advances 194
Open Questions 194
Summary 194
Further Reading 195
Relevant Website 195
Genomics of Brain Aging: Apolipoprotein E 197
Introduction 197
ApoE Expression in Different Tissues and.Cell Types and during Aging 197
ApoE and AD 197
Protein Isoforms of ApoE and Their Role in AD 198
ApoE Isoforms and Familial AD-Linked Mutations 198
Neurobiological Mechanisms: ApoE Isoform Status Influences Risk of AD by a Relatively Selective Effect on Episodic Memory 198
Neuropathological Association and Role of APOE epsi4 Allele in the Clinical Manifestation of AD 198
ApoE Genotype/Age Interaction Affects Cerebral Glucose Metabolism 199
Increased ApoE mRNA Level in AD Subjects Carrying the APOE epsi4 Allele 199
APOE epsi4 Still May Not Be a Major Susceptibility Factor for All Racial and Ethnic Groups 199
The Regulatory Region of the APOE Gene 199
Structure of the 5'-Flanking Region of the.Gene.for.ApoE 199
Promoter Polymorphisms of the APOE Gene 201
Interaction of Environmental Factor(s) with the APOE Gene Promoter 202
Interaction of the Abeta Peptide with the APOE.Promoter 202
Effects of Statins on APOE Gene Expression: Role in Regulating Inflammation and Cell Proliferation/Differentiation 202
Interaction of ApoE with Other Risk Factors: Oxidative Stress, Inflammation, and Cholesterol Transport 202
Summary 204
Further Reading 204
Genomics of Brain Aging: Twin Studies 207
The Twin Method 207
Quantitative Traits 207
Disease Traits 207
Assumptions of the Twin Method 208
Co-Twin Control 208
Candidate Genes 208
Cognitive Aging and Dementia via Twin.Models 208
Twin Studies 208
Contributions of Genes and Environments 208
General cognitive abilities 208
Specific cognitive abilities 209
Cognitive change 209
Endophenotypes of cognitive aging 210
Cognitive functioning 210
Dementia 211
Measured Genes 211
Cognitive aging and decline 211
Cognitive functioning 211
Dementia 212
Measured Environmental Factors 212
Cognitive aging and decline 212
Dementia 212
Gene-Environment. Interplay 213
Conclusion 213
Further Reading 213
Relevant Websites 213
Sensory Aging: Hearing 215
Presbycusis 215
Causes 215
Prevalence 215
Research Issues 215
Anatomy and Physiology 216
Outer Ear and Middle Ear 216
Inner Ear 216
Auditory Nerve 217
Perception 217
Psychoacoustics 217
Absolute auditory thresholds 217
Frequency selectivity and discrimination 218
Loudness and intensity discrimination 219
Temporal processing 219
Speech Processing 219
Interactions between Auditory and Cognitive.Processing 220
Rehabilitation 220
Further Reading 220
Sensory Aging: Vision 221
Introduction 221
Outer Retina 221
Photoreceptors 221
Aging Changes in Photoreceptors 221
AMD-Related Changes in Photoreceptors 221
Retinal Pigment Epithelium 222
RPE Functions Essential for Survival and Function of Photoreceptors 222
Visual cycle 222
Absorption of short-wavelength light 222
Blood-retinal. barrier 223
Age-Related Changes in the RPE 223
Age-related cell loss 223
Increased oxidative damage 223
Lipofuscin accumulation 224
A2E: Fluorophore by-product of the visual cycle 224
Toxicity of A2E 225
The RPE in AMD 225
Bruch's Membrane and Choriocapillaris 225
Age-Related Changes in the Choriocapillaris 225
Aging changes in Bruch's membrane 226
Inflammation in Drusen and AMD 227
Complement Activation 227
Normal Aging of the Inner Retina 228
Age-Related Changes of the Inner Retina 228
Diseases of Aging Inner Retina 229
Glaucoma 229
Risk Factors for Primary Open Angle Glaucoma 231
Treatments for Glaucoma 231
Neuroprotection or Rescue of RGCs 231
Vitreous Humor 231
Age-Related Changes 231
Lens 232
Normal Aging of the Lens 232
Diseases of Aging Lens 233
Risk Factors and Prevention 233
Presbyopia 234
Cornea 234
Normal Aging of the Cornea 234
Further Reading 234
Relevant Websites 234
Sensory Aging: Chemical Senses 237
Introduction 237
Age-Related Alterations in Olfaction 237
Age-Related Alterations in Taste 237
Alterations in Olfactory and Gustatory Function in Alzheimer's Disease 240
Causes of Olfactory Deficits in Aging and Alzheimer's Disease 241
Causes of Taste Deficits in Aging and Alzheimer's Disease 242
Further Reading 243
Neuromuscular Junction (NMJ): Aging 245
Aging Effects on Motor Units 246
Structure of Neuromuscular Junctions 247
Aging Effects on NMJ Structure 248
Neuromuscular Transmission 248
Aging Effects on Neuromuscular Transmission 249
Conclusions 249
Further Reading 249
Aging and Memory in Animals 257
Introduction 257
Cognitive Aging - A.Neuropsychological Framework 257
Individual Variability in Cognitive Aging 258
Neurophysiology of Cognitive Aging 259
Horizons in Research on Cognitive Aging 262
Aging beyond the Hippocampus 262
Intervention 263
Further Reading 263
Aging and Memory in Humans 265
Memory Systems 265
Long-Term Memory 265
Declarative Memory 265
Semantic memory 265
Episodic memory 266
Source memory 266
Nondeclarative Memory 267
Procedural memory 267
Priming 267
Short-Term Memory 268
Summary and Course 268
Moderators and Mediators of Cognitive.Aging 269
Further Reading 269
Cognition in Aging and Age-Related Disease 271
Introduction 271
Cognitive Declines with Healthy Aging 271
Domain-General Theories of Cognitive Aging 271
Sensory deficits 271
Inhibition 271
Speed of processing 272
Domain-Specific Theories of Cognitive Aging 272
Word-finding difficulties and transmission deficits 272
Contextual memory and associative binding deficits 273
Preserved Cognitive Function with Healthy Aging 273
Crystallized Intelligence 273
Emotion Regulation 273
Neural Changes with Healthy Aging 274
Changes in Prefrontal Cortex 274
Medial Temporal Lobe Changes 274
Changes in Emotion Processing Regions 275
Mild Cognitive Impairment 275
Alzheimer's Disease 275
Cognitive Changes in AD 275
Episodic memory 275
Semantic memory 276
Working memory and executive function 276
Neural Changes in AD 276
Neural Changes in Later-Stage AD 276
Individual Differences in Aging 276
Further Reading 277
Declarative Memory System: Anatomy 279
Introduction 279
The Amygdala, Hippocampus, and Development of an Animal Model of Human Amnesia 280
The Entorhinal Cortex 282
Boundaries and connections 282
The Perirhinal and Parahippocampal Cortices 283
Lesion studies 283
Boundaries and connections 284
Neuroanatomy of Declarative Memory 285
Further Reading 287
Episodic Memory 289
What Is Episodic Memory? 289
Reconstructing Memories Using Retrieval Cues 289
Components of Remembering 290
Strategic Processing 290
Contents of Remembering 291
Retrieval Success (Ecphory) 291
Retrieval Mode 292
Associative Nature of Memory 293
Further Reading 293
Semantic Memory 295
Introduction 295
Semantic Memory and the Medial Temporal Lobe Memory System 295
Cortical Lesions and the Breakdown of Semantic Memory 295
Object Concepts 296
Semantic Dementia and the General Disorders of Semantic Memory 296
Category-Specific Disorders of Semantic Memory 297
Models of category-specific disorders 297
Functional neuroanatomy of category-specific disorders 297
Organization of Conceptual Knowledge: Neuroimaging Evidence 298
Object Knowledge Is Organized by Sensory and Motor-Based Properties 298
Neural Networks for Animate Entities and Tools 298
Linking Category-Related Representations to Sensory and Motor Properties 300
Further Reading 300
Short Term and Working Memory 301
Introduction 301
Definition 301
Historical Backdrop 301
Current State of Working Memory Research 301
Visual Working Memory 301
Tactile Working Memory 304
Auditory Working Memory 304
Multiple Encoding in Working Memory 305
Working Memory and Prefrontal Cortex 305
Conclusion 307
Further Reading 307
Language in Aged Persons 309
Introduction 309
Theories of Cognitive Aging 309
The Nature of Language Processing 310
Age-Related Change in Language Processing 310
Language Comprehension and Memory 310
Word processing 310
Syntactic processing 310
Textbase processing 311
Situation model 312
Discourse structures and context 312
Recap 313
Language Production 313
Conclusion 313
Further Reading 314
Dementia and Language 315
Effects of Dementia on Language 315
Differential Effects 316
Alzheimer's Dementia 316
Parkinsonian Dementia 317
Frontotemporal Dementias 317
Primary nonfluent aphasia 317
Semantic dementia 318
Other dementias: vascular dementia and Lewy body disease 318
Interactions and Interventions 318
Implications and Conclusions 319
Further Reading 319
Relevant Websites 320
Aging: Brain Potential Measures and Reaction Time Studies 321
Brain and Cognitive Aging 321
EEG and ERP methods 321
Processing Speed and Reaction Time 321
Sensory Memory 322
Working Memory 322
Declarative: Episodic Memory 323
Conclusions 325
Further Reading 325
Neuroendocrine Aging: Pituitary Metabolism 327
Overview 327
GH and IGF-1 328
Invertebrate Studies 328
Mammalian Studies: Background 328
Effects of Age on the GH/IGF-1 Axis 329
Actions of GH and IGF-1 in Older Animals 330
Animal Models of GH/IGF-1 Excess and Deficiency 330
Insulin and Glucose Regulation 332
Endocrine Effects of Moderate Caloric Restriction: Interactions with Insulin and IGF-1 333
Prolactin 333
Basic Regulation and Actions 333
Prolactin Secretion and Aging 334
TSH: Tri-iodothyronine, Thyroxine, and Thyroid Function 334
Conclusions 335
Further Reading 335
Neuroendocrine Aging: Pituitary-Adrenal Axis. 337
Introduction 337
HPA Axis and Glucocorticoids 337
Glucocorticoid Cascade Hypothesis 337
HPA Axis in Aging Rodents 337
HPA Axis Pulsatility 338
Glucocorticoid Feedback 339
Brain Corticosteroid Receptors 339
Corticosteroid Receptor Balance and Aging 339
Modulation of Brain Corticosteroid Receptors and HPA Axis: Implications for Aging 340
Glucocorticoids and Aging: Mechanisms 341
Age-Related Changes during Hypercorticism: The Relevance of Context 341
Possible Mechanisms Underlying Glucocorticoid-Related Damage 341
HPA Axis, Aging, and Age-Related Pathology in Humans 342
Future Directions 343
Further Reading 343
Relevant Website 343
Neuroendocrine Aging: Pituitary-Gonadal Axis in Males 345
Overview 345
Rate of Evolution and Extent of Relative Hypoandrogenemia in Older Men 345
Mechanistic Bases of Testosterone Depletion 346
Putative Pathophysiological Mechanisms in the Aging Male 346
Hypothalamic GnRH Deficiency in Older Men 346
Enhanced Gonadotrope Secretory Responsiveness to Small Amounts of GnRH 348
Impaired Leydig Cell Steroidogenesis in Older Men 348
Aging Restricts Feedback by Endogenous Testosterone on GnRH and LH Secretion 349
FSH and Inhibin B 349
Prolactin 350
Neurohormonal Network Regulation in Aging Men 351
Summary 353
Further Reading 353
Neuroendocrine Aging: Hypothalamic-Pituitary-Gonadal Axis in Women 355
Introduction 355
Overview of the Hypothalamic-Pituitary.-Ovarian Axis in Young Women 355
Ovarian Aging and the Menopausal Transition 355
Effects of Ovarian Failure on the.Hypothalamic-Pituitary. Axis 357
Effects of Menopause on Neuronal Morphology and Neuropeptide Gene Expression in the Human Hypothalamus 358
Aging of the Reproductive Neuroendocrine Axis, Independent of the.Effects of Gonadal Status 360
Summary 360
Further Reading 360
Neuroimmune System: Aging 363
The Immune-Neuroendocrine System: The Evolutionary Perspective 363
Immunosenescence 364
Inflamm-Aging 365
Inflammation and the Neuroendocrine System 365
Major Depression 365
Anorexia Nervosa 366
Alzheimer's Disease 366
Frailty Syndrome 367
Conclusion 368
Further Reading 368
Autonomic Neuroplasticity and Aging 369
Introduction 369
Plasticity in the Developing Autonomic Nervous System 369
Neuronal Growth 369
Locally Specific Phenotype 370
Neuronal Survival 370
Plasticity in the Adult and Aging ANS 370
Neuronal Growth 370
Locally Specific Phenotype 371
Neuronal Survival in Adulthood 372
Neuronal Survival in Old Age 373
Extrinsic Factors Affecting Neuron Survival 375
Conclusions 375
Further Reading 375
Thermoregulation: Autonomic, Age-Related Changes 377
Introduction 377
'Problems' of Interpretation of Aging.Research 377
Definition of Aging 377
Designs in Research on Thermoregulation and Aging 377
Disease and Its Effect on Thermoregulation during.Senescence 378
Acclimation and the Sedentary Life Style 378
Physiology of Thermoregulation 378
Hypothalamic Regulation of Body Temperature 378
Neural Regulation of Skin Blood Flow.and.Sweat.Glands 378
Effect of Senescence on the Response to.Heat and Cold Exposure in Humans 379
Changes to Core Temperature 379
Autonomic Response 380
The onset of vasoconstriction and vasodilation .during thermal stress 380
Senescence and central-mediated autonomic response to thermal stress 380
Senescence, skin blood flow, and vasodilation response to heat 381
Senescence, skin blood flow, and the vasoconstriction response to cold 381
Summary of the Effects of Senescence on the Response to Heat and Cold Exposure in Humans 381
Effect of Senescence on the Response to Cold Exposure in Laboratory Rodents 382
Response of Core Temperature to Cold Exposure 382
Autonomic Response to Cold Exposure 382
Nonshivering thermogenesis: A.mechanism of heat production in rodents 382
Senescence and nonshivering thermogenesis 382
Vascular response to cold exposure in rats 383
Summary of Autonomic Reponses to Cold.in.Rodents 383
Response to Thermostress and the.Rate.of Aging 384
Cold-Exposed Core Temperature and Weight Loss 384
Hypothalamic function, thermoregulation, and the terminal phase 385
Conclusion 386
Further Reading 386
Sleep and Circadian Rhythm Disorders in Human Aging.and.Dementia 387
General Introduction 387
Normal Aging 387
Sleep in Normal Aging 387
Circadian Rhythms in Normal Aging 388
Excessive Daytime Sleepiness and Napping in Normal Aging 389
Causes of Sleep and Circadian Disturbances in.Older Adults 389
Alzheimer's Dementia 390
The Biological Bases of Sleep Disturbances in AD 390
Circadian Rhythm Disorder in AD 390
Other Causes of Sleep and Circadian Disturbances in AD 391
Conclusion 391
Further Reading 392
Sleep in Aging 395
Background 395
Changes in Sleep with Age 395
Changes in Circadian Rhythm 395
Treatment of Circadian Rhythm Disturbances 395
Insomnia 396
Consequences of Insomnia 396
Medical and Psychiatric Illness and Insomnia 396
Medication Use and Insomnia 397
Treatment of Insomnia 397
CBT 397
Pharmacological therapy 397
Specific Sleep Disorders 399
SDB 399
Treatment of SDB 399
Significance of SDB in development 399
Periodic Limb Movements and RLS 400
Treatment of PLMS and RLS 400
REM Behavior Disorder 400
Treatment of RBD 400
Conclusion 400
Further Reading 401
Relevant Websites 401
Erectile Dysfunction 403
Prevalence 403
Physiology of Penile Erection and Changes with Aging 403
Causes of ED 403
Medical Conditions Associated with ED 403
Evaluation 403
Treatment 405
Oral Therapy 405
Phosphodiesterase-5 inhibitors 405
Phentolamine 406
Yohimbine 406
Apomorphine 406
Medicated Urethral System for Erection 406
Intracavernous Injection Therapy 407
Testosterone Therapies 407
Effects of Testosterone Replacement 407
Coronary artery disease 407
Lipid profiles 407
Libido and ED 407
Body composition and frailty 407
Behavioral effects 408
Bone 408
Polycythemia 408
Benign prostatic hypertrophy 408
Prostate cancer 408
External Devices 408
Surgery 408
Further Reading 409
Alzheimer's Disease: An Overview 411
Major Neuropathologic Hallmarks 411
Neurotransmitter Deficits 411
Genetics 412
Abeta and Its Protein Precursor 413
Cytoskeletal Abnormalities 413
Oxidative Stress in AD 414
Conclusions 414
Further Reading 415
Relevant Websites 415
Alzheimer's Disease: Neurodegeneration 417
Neuropathology 417
The Abeta Cascade Hypothesis 420
The Tau Hypothesis 421
Timeline of Neurodegenerative Changes.in AD 421
Conclusions 422
Further Reading 422
Relevant Website 423
Axonal Transport and Alzheimer's Disease 425
Basic Features of Alzheimer's Disease 425
Axonal Transport Is Disrupted in AD 425
Roles and Effects of AD Risk Factors and Genes in Axonal Transport 427
Role of Axonal Transport Failure in AD 429
Conclusion and Perspectives 430
Further Reading 430
Aging of the Brain and Alzheimer's Disease 431
Introduction 431
Cognitive and Memory Impairments in the.Elderly 431
Alzheimer's Disease: Clinical Features, Diagnostic Studies, Neuropathology and Biochemistry, and Current Treatments 431
Genetic Causes and Risk Factors for AD 433
Biochemistry of Amyloidosis: APP and the.Secretases 434
Animal Models of Aging and AD 434
Genetic Models of Abeta Amyloidosis 435
Models of Tau Abnormalities 435
Targeting of Genes in the.Amyloidogenic.Pathway 436
BACE1.-/- Mice 436
PSEN1.-/- Mice 436
Nct..-/- Mice 436
Aph-1a...-/- Mice 436
Experimental Therapeutics 436
Reductions in BACE1 Activity 436
Inhibition of gamma-Secretase Activity 437
gamma-Secretase Modulation by Nonsteroidal Anti-.inflammatory Compounds 437
Abeta Immunotherapy 437
Conclusions 438
Further Reading 438
Alzheimer's Disease: Molecular Genetics 441
Introduction 441
beta-Amyloid Precursor Protein 441
The APOE Gene 442
The PS Genes 442
Other AD Genes 442
Animal Models 443
Further Reading 443
Relevant Website 443
Parkinsonian Syndromes 463
Introduction and Clinical Features 463
Neuroimaging 463
Pathology 464
Etiology and Pathogenesis 464
PD Genetics: Implications for PD Pathogenesis 465
Neurotoxin-Based Animal Models of PD 466
Oxidative Stress and Mitochondrial Dysfunction in PD.Pathogenesis 467
Current Treatments for PD 467
New Directions in PD Therapy 468
Further Reading 469
Relevant Websites 469
Parkinson's Disease: Alpha-Synuclein and Neurodegeneration 471
Introduction 471
The Synuclein Family 471
Parkinson's Disease and Other Lewy Body.Diseases 472
Alpha-Synuclein Mutations Cause Familial PD 472
Lewy Body Filaments Are Made of alpha-Synuclein 473
MSA 474
Synthetic alpha-Synuclein Filaments 475
Animal Models of Human alpha-.Synucleinopathies 475
Rodents and Primates 475
Flies, Worms, and Yeast 476
Outlook 476
Further Reading 476
Triplicate Repeats: Huntington's disease 479
Introduction 479
Huntington's Disease Gene 479
Clinical Features 479
Pathology 480
Theories of HD Pathogenesis: Excitotoxicity and Mitochondrial Dysfunction 481
Huntingtin 482
Posttranslational and Proteolytic Modifications of Huntingtin 482
Polyglutamines and Aggregates 483
Pathogenesis in HD 483
Transcriptional Dysregulation 483
Other Theories of Pathogenesis 483
Genetic Testing 483
Therapeutics 484
Further Reading 484
Relevant Websites 484
Huntington's Disease: Neurodegeneration 485
Huntington's Disease 485
Neurodegeneration in HD 485
Neurodegeneration in In Vitro Models.of.HD 486
Neurodegeneration in In Vivo Models.of.HD 486
Pathophysiological Mechanisms of Neurodegeneration in HD 488
Conclusion 489
Further Reading 490
Axonal Transport and Huntington's Disease 491
Introduction 491
Intracellular Transport and Neurons 491
Huntingtin and Intracellular Dynamics 491
Huntingtin Associates with the.Molecular.Motor Complex 492
Huntingtin Stimulates Axonal Transport 492
HD Pathological Situation and Axonal.Transport Defects 493
Disruption of Axonal Transport and Neurodegenerative Disorders 493
Conclusion 494
Further Reading 494
Vascular Issues in Neurodegeneration and Injury 495
Introduction 495
Pathology of Vascular Disruption Following TBI 495
Epidural Hematoma 495
Subdural Hematoma 495
Subarachnoid Hemorrhage 496
Intraparenchymal Hematoma 496
Alterations in Cerebral Blood Flow Following TBI 496
Ischemia 497
Uncoupling of Cerebral Blood Flow and Metabolism 497
Posttraumatic Vasospasm 497
Molecular Mediators of Vascular Damage.after TBI 497
Calcium 498
Prostanoid, Eicosanoid, and Reactive Oxygen.Species 498
Adenosine 499
Nitric Oxide 499
Endothelin-1 500
Neuropeptide Y 500
Endothelium-Dependent Hyperpolarizing Factor 500
Genetic Influences/Susceptibility to Vascular Changes after TBI 500
Apolipoprotein E 500
Summary 502
Further Reading 503
Stroke: Injury Mechanisms 505
Introduction 505
Excitotoxicity and Ionic Imbalance 505
Acidotoxicity 507
Apoptosis 507
Oxidative and Nitrosamine Stress 508
Inflammation 509
Peri-infarct Depolarizations 509
Contemporary Views on Stroke Pathophysiology: A.Clinical Perspective 509
Summary 510
Further Reading 510
Stroke: Neonate vs. Adult 513
Definition 513
Epidemiology 513
Presentation 513
Location, Etiologies, Workup, and.Management 513
Gender Differences 514
Mechanisms of Neuronal Injury 515
Outcome 515
Prevention 515
Future Directions 516
Further Reading 516
Aging: Invertebrate Models of Normal Brain Aging 517
Introduction 517
Neuronal Insulin-Like Signaling 517
DAF-2 Insulin Receptor Function in the.Nervous System 518
DAF-16 Targets 519
Sensory Input and Neuroendocrine Signaling 522
Other Neuroendocrine Mechanisms 522
Concluding Remarks 523
Further Reading 523
Relevant Websites 524
Cognitive Aging in Nonhuman Primates 525
Introduction 525
Visual Recognition Memory 525
Effects of Aging 526
Neural Basis 528
Spatial Memory 529
Effects of Aging 529
Neural Basis 529
Stimulus-Reward Associative Learning 530
Effects of Aging 530
Neural Basis 530
Relational Memory 531
Effects of Aging 531
Neural Basis 532
Attention/Executive Function 533
Effects of Aging 533
Neural Basis 533
Integration/Conclusions about Neuropsychological Profile of Aged Nonhuman Primates 534
Acknowledgments 534
Further Reading 534
Non-Primate Models of Normal Brain Aging 537
Introduction 537
Brain Aging in the Dog 537
Cognition and Behavior in the Aging Dog 537
Age-related learning impairments in dogs 537
Age-related memory impairments in dogs 539
Executive functions in dogs 539
Age-related changes in noncognitive behaviors in dogs 540
Neuropathology 541
beta-Amyloid deposition 541
Tau phosphorylation 541
Neuron loss and function 541
Oxidative damage 541
Neuroanatomy and Hemodynamics 542
Brain Aging in the Cat 542
Cognition and Behavior 542
Neuropathology 543
Brain Aging in Other Mammals 543
Rabbit 543
Horse 543
beta-Amyloid and Tau in Other Mammals 543
Conclusion 543
Further Reading 544
Rodent Aging 545
Introduction 545
Rodents as Models of Aging 545
The Role of the Brain in Aging and Life.Span 546
Rodent Strain Differences 546
Genetic Contributions 547
Hormonal Control 547
The hypothalamus 547
The hippocampus 547
Accelerated Aging Models and the.Oxidative Stress Theory of Aging 548
Oxidative Stress Models and ROS 548
The Senescence-Accelerated Mouse 549
Retarded Aging and Longevity Extension.Models 549
Genetic Models 549
Caloric Restriction 549
Glial Influences 550
Glial Fibrillary Acidic Protein 550
Apolipoprotein E 551
ApoE knockout and human isotype transgenic mouse models 551
Effects of human ApoE isotypes on aspects of brain aging 552
Conclusions and Relevance to Human Brain Aging 553
Further Reading 553
Transgenic Models of Neurodegenerative Disease 555
Further Reading 557
Relevant Websites 557
Animal Models of Alzheimer's Disease 559
Introduction 559
Genetically Modified Animal Models 559
APP Mouse Models and Abeta-Related Pathology 559
Mouse Models with Mutations in the Abeta Region 561
ApoE Mouse Models 562
Tau Mouse Models 562
Other Mouse Models 563
Conclusions 564
Further Reading 564
Relevant Website 565
Alzheimer's Disease: Transgenic Mouse Models 567
Creation of Transgenic Mouse Models 567
Biological Foundation 567
Technical Methodology 567
Characteristics of Transgenic Mouse.Models 567
APP Transgenic Mice 567
Tau Transgenic Mice 568
Other Types of Transgenic Mice 569
Utility of Transgenic Mouse Models 569
Validity of Transgenic Mouse Models 569
Relevance of Transgenic Mouse Models 570
Testing Experimental Therapies in Transgenic Mouse Models 570
Mechanism of Memory Loss in Transgenic Mouse.Models 570
Further Reading 571
Animal Models of Parkinson's Disease 573
Introduction 573
PD 573
DA Depletion 573
Reserpine 573
Nigral Cell Loss 574
6-Hydroxydopamine 574
1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine 575
The MPTP mouse model 575
The MPTP primate model 576
Environmental Toxin Models 577
Rotenone 578
Paraquat and maneb 578
Protein Aggregation 578
Transgenic Animals 578
Alpha-synuclein transgenic models 578
Parkin and ubiquitin C-terminal hydrolase L1 transgenic models 579
Viral Vector-Delivered alpha-Synuclein 579
Other PD Models 579
Lipopolysaccharide 579
Aged Animals 579
Animal Models of Dyskinesia 579
Conclusions 580
Further Reading 580
Animal Models of Huntington's Disease 583
N-Terminal Exon-1 Transgenic Mouse Models 584
Full-Length Transgenic Mouse Models 586
Knockin Models 589
Conclusion 589
Further Reading 589
Relevant Website 590
Animal Models of Motor and Sensory Neuron Disease 591
Motor and Sensory Tracts 591
Gene Deletion ('Knockout') and Transgenic Mouse Models 591
Neurodegeneration in Human 591
Motor Disease 591
Amyotrophic lateral sclerosis 591
Spinal muscular atrophy 595
Motor and Sensory Disease 595
Charcot-Marie.-Tooth 595
Giant axonal neuropathy 596
Conclusion 596
Further Reading 596
Animal Models of Stroke 597
Introduction 597
Can Animal Models Mimic Human Stroke? 597
Cerebral Ischemia Models: Global versus Focal Ischemia 598
Global Cerebral Ischemia 598
Complete global ischemia 598
Incomplete global ischemia 599
Focal Cerebral Ischemia 600
Middle cerebral artery occlusion 600
Common carotid artery occlusion 602
Pial strip 603
Photothrombosis 603
Embolic 603
Endothelin 603
Hemorrhagic Stroke Models 604
Conclusion 604
Further Reading 604
Cell Replacement Therapy: Parkinson's Disease 605
Introduction 605
History 605
Studies in Rodents and Primates 605
Clinical Trials 606
Future Cell Replacement Strategies 608
Further Reading 609
Neurogenesis in the Intact Adult Brain 611
History 611
Adult Hippocampal Neurogenesis 612
Adult Olfactory Neurogenesis 613
Regulation 613
Function 614
Medical Relevance 614
Further Reading 615
Neurotrophic Factor Therapy: GDNF and CNTF 617
Introduction 617
Glial Cell Line-Derived Neurotrophic Factor 617
Identification and Role 617
Distribution of GDNF in the CNS 617
GDNF and PD 618
GDNF and HD 620
GDNF and Cerebral Ischemia 620
Ciliary Neurotrophic Factor 620
Identification and Role 620
Distribution of CNTF in the CNS 621
CNTF and Amyotrophic Lateral Sclerosis 621
CNTF and HD 621
CNTF and Retinal Degenerative Diseases 622
Conclusion 623
Further Reading 623
Exercise: Optimizing Function and Survival at the Cellular Level 625
Introduction 625
Exercise and Central Nervous System Activation: Neurotransmitter Function 625
Exercise and Growth Factor Expression 626
Exercise and Cellular Survival Signaling 628
Neurodegeneration: How Exercise Can Decrease Risk and Contribute to CNS.Repair Mechanisms 629
Conclusion 629
Further Reading 630
Exercise in Neurodegenerative Disease and Stroke 631
Introduction 631
PD 631
The Condition 631
Clinical Evidence for the Beneficial Effects of Exercise in PD 631
Animal Studies 632
AD 633
The Condition 633
Clinical Findings on Efficacy of Exercise in AD 633
Animal Studies 634
Stroke 634
Exercise 634
Animal Studies 635
How Might Exercise Work? 636
Exercise Regulates Trophic Factors 637
Summary and Conclusions 638
Further Reading 638
Hormones and Memory 641
Background 641
Estrogen and Declarative Memory 641
Effects of Estrogen on Memory during Normal Menstrual Cycling 641
Effects of Estrogen in the Perimenopausal Period 641
Effects of Estrogen on Older (Postmenopausal) Women 642
Estrogen and Working Memory 643
Estrogen and Implicit Learning 643
Sex Hormone Effects in Men 643
Concluding Comments on Sex Hormones.and Memory 643
Further Reading 644
Deep Brain Stimulation and Movement Disorder Treatment 645
History and Development 645
Description 645
Indications and Targets 645
Anatomy and Pathophysiology 645
Mechanism of Action 646
Operative Procedure 647
Advantages, Disadvantages, and Alternatives 648
Outcomes 649
Further Reading 649
Deep Brain Stimulation and Parkinson's Disease 651
Introduction 651
Methodological Aspects 651
Selection of PD Patients for Surgical Therapy.with.DBS 651
Surgical Issues 652
Postoperative Management 653
Results of Bilateral DBS in PD 654
Bilateral DBS of the STN 654
Bilateral DBS of the GPi 656
Adverse Events 659
Surgical and Device-Related AEs 659
Stimulation and/or Disease-Related AEs 659
Further Reading 660
Subject Index 661
| Erscheint lt. Verlag | 22.5.2010 |
|---|---|
| Sprache | englisch |
| Themenwelt | Sachbuch/Ratgeber |
| Geisteswissenschaften ► Psychologie ► Biopsychologie / Neurowissenschaften | |
| Medizin / Pharmazie ► Medizinische Fachgebiete ► Geriatrie | |
| Medizinische Fachgebiete ► Innere Medizin ► Endokrinologie | |
| Medizin / Pharmazie ► Medizinische Fachgebiete ► Neurologie | |
| Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie | |
| Studium ► 1. Studienabschnitt (Vorklinik) ► Histologie / Embryologie | |
| Naturwissenschaften ► Biologie ► Humanbiologie | |
| Naturwissenschaften ► Biologie ► Zoologie | |
| Sozialwissenschaften ► Politik / Verwaltung | |
| Sozialwissenschaften ► Soziologie | |
| ISBN-10 | 0-08-095405-7 / 0080954057 |
| ISBN-13 | 978-0-08-095405-9 / 9780080954059 |
| Haben Sie eine Frage zum Produkt? |
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