Brain, Vol. 123, No. 8, 1752-1753,
August 2000
© 2000 Oxford University Press
Book reviews |
ALZHEIMER DISEASE. Second edition.
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Dementia Research Laboratory, Biochemical Neuropharmacology Group, Centre for Neuroscience, King's College London, London, UK
This is the second edition of a book, the first edition of which was published in 1994. The first edition was very successful and found its way onto many bookshelves as an authoritative reference on Alzheimer's disease. Research in this field has progressed very rapidly during the intervening period. Furthermore, we now have several drugs available for the symptomatic treatment of Alzheimer's disease. Attempting a new authoritative reference is therefore timely and represents an opportunity to incorporate new discoveries with reassessment and consideration of well-known facts. It is very likely that this book will also prove a valuable addition to many libraries and bookshelves, not the least because of the very extensive reference list at the end of most chapters. Those of us who work in the field are acutely aware of the breadth of knowledge that we have to assimilate to begin to understand this most complex and challenging disease. For example, the basic scientist should ideally have a grasp of the clinical features of the disease covering aspects of neurology, psychiatry and psychology, while the clinician should be able to converse with biochemists, molecular biologists, protein chemists and so on. With the availability of this book there is less excuse for the two groups not to interact.
The book consists of 29 chapters covering most aspects of Alzheimer's disease research. It is a little disappointing that all contributors are based in North America; was this deliberate or could no scientists or clinicians of sufficient standing be found in the rest of the world? Having said that, the editors are to be commended for having assembled a highly distinguished panel of experts covering most disciplines contributing to our current knowledge and understanding of Alzheimer's disease.
The first chapter is a real gem, covering the early history of Alzheimer's disease (more of which later). The next section of chapters deals with clinical issues relating to diagnosis, symptoms, genetics and epidemiology. There is then a section of chapters dealing with other causes of dementia that may overlap with Alzheimer's disease or be mistaken for it: these include vascular dementia, frontal lobe dementias, prion diseases and dementia with Lewy bodies. The next group of chapters deals with neuroanatomical considerations and relationships to cognitive impairment both in man and in primates and transgenic mouse models. Neurochemical studies of transmitters and proteins involved in Alzheimer's disease are given extensive coverage, together with integration of the potential roles of inflammation and oxidative stress as disease-causing mechanisms. The final two chapters report on treatment of Alzheimer's disease patients in terms of cognitive and non-cognitive symptoms together with future disease-modifying/preventing strategies. We have selected several chapters for more detailed consideration to give a `flavour' of the whole book.
The chapter entitled `The early history of Alzheimer's disease' is a scholarly and most interesting account of the early years, dealing with the naming and distinction of the disease we now call Alzheimer's disease from other forms of dementia. Dr Bick provides intriguing insights, culled from original texts, into the minds of the various players and gives due credit to the work of Alzheimer's distinguished co-workers, including Perusini, who was the author of the detailed pathological report on the index case (Auguste D.). Perhaps Dr Bick could be persuaded to provide a similar critical analysis of Alzheimer research during the period 1970–2000, although with the exponential growth of research and researchers this would be a challenging task. This chapter is a `must' for all workers in the field.
Dr Morris provides a comprehensive analysis of the clinical presentation and course of Alzheimer's disease. He begins by challenging a long-held tenet that the diagnosis of Alzheimer's disease is by exclusion, although he admits that there is considerable difficulty with early dementia and in cases with mixed pathology. However, the author has extensive experience of examining cognitive performance in the non-demented elderly and provides considerable insight into the challenge of early differential diagnosis. The author helpfully provides a section dealing with `core' features of Alzheimer's disease and the possible molecular bases for heterogeneity. Finally, issues concerning diseases that overlap with Alzheimer's disease are addressed, together with the utility of diagnostic procedures and the lack of available biomarkers.
Two chapters deal with the important issue of non-cognitive symptoms, such as aggression and psychosis. Such symptoms are common, particularly troublesome to carers and potentially treatable. Both Drs Folstein and Bylsma and Dr Rabins detail the incidence and impact of such behaviours on patients and carers. While there is a reasonable discussion of the existing methods for quantifying non-cognitive behavioural symptoms, neither mention the widely-used Neuropsychiatric Inventory nor the Present Behaviour Examination as tools. Both discuss management of patients and highlight the need to include the patient and family members in the scheme. Both chapters emphasize the use of non-pharmacological methods for treatment and practical suggestions for management and the expected advice on choice of medication.
Drs Salmon and Bond provide a good discussion of clinicopathological correlates. The authors emphasize that Alzheimer's disease is characterized by dysfunction of both episodic and semantic memory, with clear examples of how these changes affect the performance of patients in particular tasks. How these changes link to damage to particular brain regions is also given. The authors provide evidence that detectable cognitive decline can precede clinical diagnosis of Alzheimer's disease by several years and demonstrate that application of such tests would be invaluable to aid screening and drug development. Finally, there is a section on distinguishing the memory impairments associated with Alzheimer's disease from those found in Huntington's disease and Lewy body dementia.
The biochemical pathology and genetics of Alzheimer's disease are extensively covered in a series of chapters by prominent researchers in their respective individual fields. For example, Drs Geula and Mesulam have contributed an outstanding chapter on dysfunction of the cholinergic system in Alzheimer's disease. The authors provide a very detailed examination of the demise of the basal forebrain cholinergic system in relation to other neurotransmitter systems, the potential relevance of loss of cholinergic function to changes in cognition, and an overview of a potential role of neurotrophins, in particular nerve growth factor, in cholinergic neuronal atrophy and/or degeneration. Following up on the neurotrophin theme, Drs Peterson and Gage provide a topical review of the therapeutic potential of neurotrophic factor therapy for the treatment of neurodegenerative disorders. The authors outline, in considerable detail, the rationale for neurotrophin treatment based on lesioned animal models, as well as a brief consideration of the major strategies for delivering such factors to the brain, including direct protein infusion and both in vivo and ex vivo gene transfer. This latter topic comes at an opportune time with the recent approval of phase I clinical trials of NGF-gene therapy for patients in the early stages of Alzheimer's disease.
Dr St George-Hyslop provides a detailed analysis of the molecular genetics of Alzheimer's disease, including known mutations in APP, presenilins and other as yet unidentified gene products. The table of known mutations in the presenilin genes and their associated phenotypes is particularly useful.
Dr Thal discusses the background to clinical trials in Alzheimer's disease including the inherent problems, design and outcome measures for different types of trial. The author draws on his considerable experience of clinical trials with cholinergic drugs but also reviews other current approaches together with newer, disease prevention, strategies.
Overall, this is an excellent, timely update of a `standard reference' with few, if any, weaknesses. It is likely to be a valuable reference for several years to come. However, one may assume that the editors are already planning the next update that will cover such intriguing items as the background to and results of clinical trials of immunization with Ab.
Notes
Edited by Robert D. Terry, Robert Katzman, Katherine L. Bick and Sangram S. Sisodia. 1999. Philadelphia: Lippincott Williams & Wilkins. Price $145. Pp. 480. ISBN 0-7817-1503-2.
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