GERONTOLOGY

Gerontology

1.

The concept of disease begins with people and their minds. First, the notion of disease, or ''dis-ease, '' implies that we start with the suffering of an individual human being. Lay concepts of illness are critical to understanding the behavior of patients and their families, and it is these ideas that largely determine what sort of cases come into the view of the clinician. However, once the patient appears before the clinician, it is the professional's identification of a condition as a disease that dominates society's models of illness (or at least the public discourse about disease). Thus, the scientific concept of Alzheimer disease (AD) begins with the clinical characterization of a pattern of progressive cognitive impairment. This pattern occurring in the elderly has been described in literature extending back for centuries. The second critical aspect of the development of the initial concept of AD was the application of labels to characterize the disease state. The term dementia, implying loss of mentation, predate AD. Perhaps fifty years before Alzheimer's time, other clinicians had characterized this loss of cognitive abilities and had begun to differentiate it from other clinical conditions. For example, dementia differentiated from amentia, or mental retardation; that is, dementia requires normal intellect and deterioration to an impaired level of thinking ability. Dementia was also differentiated from delirium, which defined as changes in cognition occurring often acutely in response to medical illness. Thus, the initial characterization of neuropsychiatry diseases depended on the skills of clinicians or others to observe individuals and to cluster their symptoms into certain categories. However, the development of methods to examine brain tissue allowed the concept of clinical pathological, entities to emerge.

Inside every large problem are dozen of small ones struggling to get out. This corollary to Murphy's law might well seem applicable to progress in Alzheimer disease (AD), except that in this case, it is difficult to discern if the problems solved are bigger than the ones set loose. The chapters in this section consider the tremendous prospects for progress in the biomedical science of AD, particularly in the area of molecular genetics. But they also consider the sorts of challenges this progress may create in the realms of politics and ethics. Larry Altstiel and Steven Paul provide a cogent description of recent progress. Their chapter describes how molecular biology has revolutionized AD research, surveying the current state of the field and the prospects for developing therapeutic agents that not only relieve some of the symptoms of cognitive decline but also slow disease progression and reduce its incidence. The identification of specific gene mutations and proteins involved in AD, the development of a transgenic mouse to test new drugs that models both AD pathology and cognitive decline, and explorations of the role of estrogen in the maintenance of the neurons affected by AD, all these provide ample reason to hope that new and effective therapeutic strategies will be developed in the foreseeable future. Although these strategies are a result of the new biology, ...