Cover

Half-title

Title

Copyright

Contents

Contributors

Preface

SECTION 1 Cognition and the brain: measurement, tools, and interpretation

1 Introduction

REFERENCES

2 Clinical neuropsychology

Historical background

Goals of assessment

Standard neuropsychological evaluation procedures

Commonly used neuropsychological tests by domain assessed

Intelligence

Attention and processing speed

Visual ability

Language

Memory

Executive function

Sensorimotor ability

Mood and personality

REFERENCES

3 Brain imaging investigation of chemotherapy-induced neurocognitive changes

Introduction

Structural and functional neuroimaging methods

Neuroimaging of cognitive changes related to cancer and chemotherapy

MRI studies of childhood leukemia

Neuroimaging in osteosarcoma

Other MRI reports of chemotherapy-induced leukoencephalopathy in adults

Structural and functional MRI studies of chemotherapy-related cognitive changes in breast cancer

Conclusion

ACKNOWLEDGMENTS

REFERENCES

4 Role of neuropsychological assessment in cancer patients

Benefit of neuropsychological assessment for clinical medical management of the cancer patient

Neuropsychological dysfunction at presentation

Cancer surveillance using neuropsychological assessment

Neuropsychological side-effects of cancer treatment

Discrimination of neurocognitive from psychological sequelae

Prognostic value of neuropsychological assessment

Benefit of neuropsychological assessment to the clinician

Benefit of neuropsychological assessment for the patient and family caregivers

Benefit of neuropsychological information to clinical cancer and survivorship research

REFERENCES

5 Neuropsychological assessment of adults with cancer

Introduction

Neuropsychological assessment

Principles of neuropsychological assessment in the cancer population

Test selection

Assessment process

Timing of assessment(s)

Cognitive domains of interest

Patient-reported outcomes

Disease- and treatment-specific considerations

The assessment of patients with CNS disease

The impact of radiation on cognitive function

Impact of chemotherapy on cognitive function

Impact of immunotherapy and hormonal therapies on cognitive function

Fatigue

Anemia

Adjunctive medications

Affective distress

Conclusion

REFERENCES

6 Neuropsychological assessment of children with cancer

Introduction

Childhood cancer

Brain tumors

Acute lymphoblastic leukemia

Pattern of neuropsychological deficits

Implications for neuropsychological assessment

Serial assessments

Liaison with the school

Approaches to assessment

Areas to evaluate

Overall intellectual functioning

Learning and memory

Core cognitive processes: attention, processing speed, working memory

Attention

Working memory

Processing speed

Executive function

Language

Non-verbal skills: visual perceptual, visual motor, visual spatial, and visual constructional abilities

Motor and sensory perceptual function

Academic achievement

Psychosocial and adaptive functioning

The Children's Oncology Group (COG) neuropsychology test battery

Oregon Health Sciences University test battery

Future directions in pediatric oncology and neuropsychology

REFERENCES

SECTION 2 Effects of cancer and cancer treatment on cognition

7 Biological bases of radiation injury to the brain

Introduction

Pathogenesis of radiation-induced CNS injury

Classical model of parenchymal or vascular target cells

Vascular hypothesis

Parenchymal hypothesis

Astrocytes

Microglia

Neurons

Neural stem cells and neurogenesis

Contemporary view on the pathogenesis of radiation-induced CNS injury

Laboratory studies of therapeutic interventions for radiation-induced CNS injury

Clinical aspects of CNS radiation tolerance

Quantitative scoring of CNS toxicity

Conclusions

ACKNOWLEDGMENTS

REFERENCES

8 Cognitive dysfunction related to chemotherapy and biological response modifiers

Chemotherapy-related cognitive dysfunction

Incidence and nature of chemotherapy-related cognitive dysfunction

Risk factors and mechanisms underlying cognitive and neurobehavioral toxicity

Neuroimaging and neurophysiologic correlates of chemotherapy-related cognitive dysfunction

Pharmacogenetic modulation of chemotherapy-related cognitive dysfunction

Biological response modifiers

Interferon alpha

Interferon-related side-effects

Nature and course of interferon-related cognitive dysfunction

Mechanisms underlying cognitive and neurobehavioral toxicity

Intervention strategies to prevent or manage cognitive and neurobehavioral dysfunction

REFERENCES

9 Effect of hormones and hormonal treatment on cognition

Introduction

The role of reproductive hormones in cognitive function

The influence of reproductive hormones on cognition in healthy women

The influence of reproductive hormones on cognition in healthy men

Neuroimaging studies

Conclusions

Hormonal therapy in breast and prostate cancer: is there an influence on cognitive function?

The role of hormonal therapies in cancer treatment

Hormonal therapies in breast cancer: the influence on cognitive functioning

Hormonal therapies in prostate cancer: the influence on cognitive functioning

Methodological aspects

Sample size

Cross-sectional versus prospective studies

Selection of cognitive measures

Self-reported cognitive complaints

Anxiety, depression, fatigue, and psychosocial distress

Comparisons of group means versus analysis of test scores of individuals

Conclusions

REFERENCES

10 Low-grade gliomas

Introduction

Epidemiology and biology, pathology and genetics, clinical and imaging features, prognostic factors in LGG

Epidemiology and biology

Pathology and genetics

Clinical and imaging features

Prognostic factors in LGG

Therapeutic management

Surgery

Radiotherapy

Chemotherapy

Neurocognitive disturbances in LGG

Primary tumor as a cause of neurocognitive deficits

Surgery as the cause of neurocognitive deficit

Radiation as the cause of cognitive deficit

Medical therapy as a cause of neurocognitive disturbances

Anti-epileptic drugs

Chemotherapy

Mood disorder as a cause of neurocognitive disturbances

Conclusion

REFERENCES

11 High-grade gliomas

Introduction

Scope of the problem

Causes of cognitive impairment in patients with high-grade gliomas

Assessment of cognitive function in patients with high-grade gliomas

Importance of neurocognitive assessment

Treatment of cognitive deficits in patients with high-grade gliomas

Summary

REFERENCES

12 Brain metastases

Introduction

Overview of brain metastases

Epidemiology

Clinical presentation

Prognosis

Treatment

Neurocognitive impairment in brain metastases

Incidence

Etiology and pathogenesis

Neurocognitive deficits due to cancer

Cognitive sequelae of cancer therapy

Radiotherapy

Systemic anti-cancer therapy

Surgery

Adjuvant medications

Management of neurocognitive deficits

Methylphenidate

Donepezil

Hyperbaric oxygen

Transplantation of purified oligodendrocytes

NMDA receptor

Prevention of neurocognitive de.cits

Radiation dose and fractionation

Radiosurgery alone

Erythropoietin

Conformal avoidance of the hippocampus

Conclusion

REFERENCES

13 Primary central nervous system lymphoma

Introduction

Diagnosis and treatment

Treatment-related delayed neurotoxicity

Cognitive functions in PCNSL

Prospective studies

Retrospective studies

Cognitive outcome and treatment-related white matter abnormalities

Conclusion

REFERENCES

14 Childhood brain tumors

Medical late effects

Secondary malignancies

Cardiac complications

Pulmonary complications

Endocrine complications

Disorders of hearing and sight

Renal complications

Gastrointestinal and hepatic complications

Neurological complications

Neuropsychological late effects

Neurocognitive late effects

Psychosocial late effects

Interventions

Summary

REFERENCES

15 Neurofibromatosis

Introduction

History

Phenotype and genotype

The NF-I gene

Systemic impact

Focal growth dysregulation in benign tumors

Brain malformation in animal models of NF-I and humans

Brain tumors in NF-I

Systemic impact on function

Neurocognitive status of children with NF-I

Intellectual functioning

Learning and academic achievement profile

Visual-spatial abilities and their impact on academic achievement

Brain structure/function correlates

Brain tumors

MR hyperintensities

Macrocephaly

Congenital malformation

Functional imaging studies

Summary

ACKNOWLEDGMENTS

REFERENCES

16 Hematological malignancies

Introduction

Neurological complications independent of cognitive deficits

Cognitive deficits

Cognitive effects of treatment

Chemotherapy

Radiation therapy

Hematopoietic stem cell transplantation

Biological treatments

Anemia and iron deficiency

Immune response

Treatment for cognitive and emotional dysfunction

Summary

REFERENCES

17 Paraneoplastic disorders

Introduction

Paraneoplastic limbic encephalitis

Pathology

Clinical features

Diagnostic studies

Autoimmunity

Differential diagnosis

Patient management

Paraneoplastic opsoclonus-myoclonus

Clinical features

Pathology

Autoimmunity

Patient management

REFERENCES

18 Symptomatic therapies and supportive care issues

Introduction

Delirium

Common causes of delirium in cancer patients

Assessment of delirium

Delirium rating scales

Laboratory assessment and other tests

Management of delirium

Pharmacotherapy

Depression

Disease- and treatment-related factors

Cancer/treatment-related causes of dementia and cognitive impairment

Antineoplastic therapies

Supportive care drugs

Palliative care settings

Symptomatic pharmacotherapy

Future research

Detection and screening

Treatment

Communication/education

Conclusion

REFERENCES

19 Animal models and cancer-related symptoms

Why use animal models?

Animal models

Models of depression

Stress

Animal tests of depression

The Porsolt forced swim test

The tail suspension test

Cognitive tests

Tests of learning and memory

Other cognitive tasks

Tests for fatigue

Conclusions

ACKNOWLEDGMENTS

REFERENCES

SECTION 3 Interventions and implications for clinical trials

20 Behavioral strategies and rehabilitation

Definition of cognitive rehabilitation

Cognitive rehabilitation in TBI/CVA

Strategy training for attention deficits

Strategy training for memory and learning inef.ciencies: the memory notebook

Formal problem solving for executive functioning deficits

Cognitive rehabilitation in degenerative conditions

External memory aids

Cognitive rehabilitation versus mental stimulation

Cognitive rehabilitation for patients with cancer

Clinical application of cognitive rehabilitation strategies in cancer patients

Appendix A

Session 1

Session 2

Session 3

Sessions 4–6

Appendix B

Problem-solving therapy intervention protocol

Session 1

Session 2

Session 3

Sessions 4–6

REFERENCES

21 Support services

Introduction

Needs assessment

Support needs across the disease continuum

Newly diagnosed/pre-treatment

Active treatment

Post-treatment stable disease

End of life/palliative care

Support settings/contexts

Community re-entry/integration

School settings

Work settings

Family settings

Modalities of support

Psychosocial support

Rehabilitation programs

Complementary and alternative approaches

ACKNOWLEDGMENTS

RESOURCES

REFERENCES

22 Pharmacological interventions for the treatment of radiation-induced brain injury

Introduction

Symptoms and symptom clusters in brain tumor patients

Management of radiation-induced brain injury

Acute reactions

Early delayed reactions

Late delayed reactions

ACKNOWLEDGMENT

REFERENCES

23 Neurocognitive testing in clinical trials

Importance of formal neurocognitive testing

Choice of neurocognitive tests

Psychometric properties

Focal versus diffuse function

Impact of disease and treatment

Frequency of testing

Study design: baseline versus repeated testing

Implementation in clinical trials

Required personnel and training

Data collection

Statistical and interpretive considerations

Confounding variables and missing data

Analytical approaches

Reliable change index

Regression-based methods for predicting change scores

Time-to-event analyses

Repeated measures analyses

Growth mixture modeling

Q-TWiST methods

Conclusions

REFERENCES

Index