The Dementias: Early Diagnosis and Evaluation

Univ. of Manchester, UK. Presents the latest techniques and technologies for dementia identification and evaluation, including neuropathological strategies, neuropsychological tests, biomarkers, CT, MRI, functional MRI, PET, and SPECT. Provides findings for assessment of Alzheimer's disease, dementia with Lewy bodies, vascular dementia, and more. For neurologists.

Preface

iii

Acknowledgments

v

Contributors

xiii

The Clinical Issues

1

(32)

Norman L. Foster

Introduction

1

(1)

Dementia Evaluation

2

(12)

Difficult Diagnostic Crossroads and Decision Points

14

(11)

Summary

25

(1)

References

26

(7)

Neuropsychological Screening and Advanced Neuropsychological Tests

33

(40)

Daniela Perani

Introduction

33

(1)

Neuropsychological Assessment

34

(11)

Assessment of Psychological and Behavioral Disturbances

45

(1)

Functional Scales

46

(2)

The Role of Neuropsychological Assessment of Dementia

48

(8)

Advanced Tests and Future Research Approaches

56

(4)

Conclusions

60

(1)

References

60

(13)

Biomarkers in Blood and Cerebrospinal Fluid

73

(36)

Harald Hampel

Katharina Buerger

Introduction

73

(1)

β-Amyloid Peptide 40 and 42

74

(3)

Amyloid Protein Precursor

77

(1)

Tau Proteins

78

(4)

Apolipoprotein E

82

(1)

Isoprostanes

83

(1)

α1-Antichymotrypsin

83

(1)

The Soluble Interleukin-6 Receptor Complex

84

(1)

C-Reactive Protein

85

(1)

C1q

85

(1)

Homocysteine

86

(1)

Oxysterols and Cholesterol Metabolism

87

(1)

3-Nitrotyrosine

88

(1)

14-3-3 Protein in Creutzfeldt-Jakob Disease

89

(1)

Perspective of Biomarker Research in AD: β-Amyloid Antibodies

89

(1)

Discussion

90

(4)

References

94

(15)

Genetics: Facts and Perspectives

109

(28)

Sandro Sorbi

Paolo Forleo

Francesca Massaro

Andrea Ginestroni

Introduction

109

(20)

Summary

129

(1)

References

129

(8)

Approaches to the Identification of Novel Diagnostic and Therapeutic Targets in Dementia

137

(20)

Kate E. Wilson

Chris Morris

Introduction

137

(1)

Functional Genomics

138

(1)

Microarray-Based Gene Expression Profiling

138

(4)

Proteomics

142

(5)

Fluid Analysis

147

(3)

Conclusions

150

(1)

References

151

(6)

Quantitative and Functional Magnetic Resonance Imaging Techniques

157

(40)

Giovanni B. Frisoni

Nicola Filippini

Image Acquisition: Technical Features

157

(6)

Quantitative Magnetic Resonance Imaging Tools to Rate Regional Atrophy and Cerebrovascular Disease

163

(7)

Quantitative Magnetic Resonance Imaging for the Clinical Diagnosis

170

(9)

Microstructural Imaging: Diffusion and Magnetization Transfer Imaging

179

(3)

Functional Magnetic Resonance Imaging in Dementias and Mild Cognitive Impairment

182

(6)

References

188

(9)

Perfusion Imaging with Single Photon Emission Computed Tomography

197

(32)

Nadine J. Dougall

Klaus P. Ebmeier

Single Photon Emission Computed Tomography

197

(1)

Blood Flow Tracers

198

(1)

Alzheimer's Dementia

199

(3)

Techniques to Improve Diagnostic Accuracy

202

(2)

Cohort Studies

204

(1)

Vascular Dementia

204

(6)

Frontotemporal Dementia

210

(5)

Dementia with Lewy Bodies

215

(1)

Mild Cognitive Impairment

215

(7)

Conclusion

222

(1)

References

222

(7)

FDG PET: Imaging Cerebral Glucose Metabolism with Positron Emission Tomography

229

(24)

Karl Herholz

Positron Emission Tomography

229

(1)

Measurement of Local Cerebral Glucose Metabolism

230

(1)

Main Findings in Alzheimer's Disease

231

(4)

Longitudinal Studies and Trials

235

(1)

Early Diagnosis of Alzheimer's Disease

236

(2)

Clinical Diagnostic Use of 18F-2-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography in Alzheimer's Disease

238

(1)

Dementia with Lewy Bodies

238

(1)

Frontotemporal Dementia

238

(2)

Vascular Dementia

240

(1)

Creutzfeldt-Jakob Disease

241

(1)

Summary

241

(1)

References

242

(11)

Imaging of Neurotransmitter Systems in Dementia

253

(26)

Steen G. Hasselbalch

Gitte M. Knudsen

Introduction

253

(2)

Normal Aging

255

(2)

Alzheimer's Disease

257

(9)

Lewy Body Dementia

266

(2)

Frontotemporal Dementia

268

(1)

Cognitive Dysfunction Due to Cerebrovascular Disease

269

(1)

Conclusions

270

(1)

References

270

(9)

Development and Application of β-Amyloid Imaging Agents in Alzheimer's Disease

279

(32)

William E. Klunk

Robert D. Nebes

Nicholas Tsopelas

Brian J. Lopresti

Julie C. Price

Steven T. DeKosky

Chester A. Mathis

Introduction

279

(3)

Development of Amyloid Imaging Technologies

282

(15)

Future Applications of Amyloid Imaging

297

(5)

Summary

302

(1)

References

303

(8)

A View on Early Diagnosis of Dementias from Neuropathology

311

(118)

Kurt A. Jellinger

Introduction

311

(1)

Classification of Dementia Disorders

312

(1)

Basic Pathology of Major Dementing Disorders

312

(40)

Early Pathology of AD and Clinical Correlates

352

(15)

Early Morphological Changes in Dementia Disorders and Relation to Biomarkers

367

(6)

Correlation of Clinical and Pathological Criteria

373

(1)

Effects of Concurrent Pathologies

373

(1)

Neuropathology of AD and Clinical Relevance

374

(1)

Conclusions

375

(1)

Abbreviations

375

(3)

References

378

(51)

Guideline and Perspective

429

(14)

Karl Herholz

Daniela Perani

Chris Morris

Introduction

429

(1)

Diagnosis of Mild Manifest Dementia

430

(3)

Nondemented Subjects with Cognitive Impairment

433

(3)

Asymptomatic Subjects

436

(1)

Monitoring Treatment

437

(2)

Conclusion

439

(1)

References

439

(4)

Index

443

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The Dementias: Early Diagnosis and Evaluation

Summary

Table of Contents

Supplemental Materials