Alzheimer's disease (AD) is regarded by some as 'the disease of the century'. This is reflected in the number of publications on the topic and the substantial efforts being made to discover a pharmacological treatment. The number of problems associated with this research is almost equal to the number of publications, and the authors concentrate on these difficulties, though the tone is not pessimistic. After a brief but useful overview, Chapter 2 examines the major problem of diagnosis, including informative summaries of the currently available brain imaging techniques. The main problem, as so often, is definition: even at autopsy, none of the proposed criteria have yet received universal acceptance and usage. The lack of basic animal and clinical models is discussed in Chapter 3. Those models that are available (and how to validate them) are covered, with an emphasis on pharmacological probes such as scopolamine.
The core section of the book tackles end-organ responses, with chapters on the brain (changes in structure and function) and on peripheral end-organ responses (blood cholinesterases and salivary amylase). The third part of this Section looks at 'neuropsychological' endorgan responses: the authors describe their extensive (too extensive?) neuropsychological test battery and present data showing that the Mini-Mental State Examination by itself is inadequate for accurate diagnosis.
Under the chapter heading 'Subject Selection', the authors point out some of the most important practical problems in AD research. One of the commonest reasons why a drug trial fails is inadequate recruitment. This difficulty is greatly magnified in AD research because of the nature of the population and of the disease itself. Inclusion and exclusion criteria must be carefully selected, e.g. it may be desirable that, in the case of volunteers, subjects are not taking concomitant medication. On the other hand it is very difficult to recruit many over-65s who are healthy, drug free and willing to risk their health by participation in a clinical trial. Problems of concomitant diseases, disease severity, patient compliance and sample size are also addressed, as is the thorny problem of obtaining true informed consent from AD patients. Here the authors introduce their concept of the 'bridging study', discussed more fully in a later chapter. This is effectively a late phase I trial but incorporating patients as well as healthy volunteers, the need for it arising from findings