Almost 100 years ago, Alois Alzheimer described the case of Auguste D., a woman who developed delusions and memory impairment at 56 years of age. Alzheimer went on to detail the symptoms and neuropathology of the disease that came to carry his name. For most of the subsequent century, however, little more was learned: Alzheimer's disease remained an entity with a well-described syndromal presentation, clinical course, and a distinct neuropathology but little else appreciated. Only in the past 20 years have findings regarding the pathogenesis of AD and potential treatments emerged. The emergence of standardized criteria for both the clinical diagnosis of AD and its pathological definition; the mainstreaming of a pathogenetic theory; the development of animal models; the identification of specific gene risk factors; and the first round of approved treatments have recently come to light.
This wealth of discovery has been fueled by the development of new techniques and technologies. Equally important has been the shift in attitude regarding cognition in the elderly. The notion of “senility” has been largely supplanted by a growing appreciation that cognitive decline is not the rule and is indicative of a distinct disease process. This realization spurs the research to determine who declines, who does not, and the risks factors for decline. This paradigm shift has allowed a renewed focus on disease processes related to memory decline in aging, and particularly AD. This issue of CNS Spectrums focuses on the shift in thinking about AD. We are on the cusp of a dramatic change in our understanding of the risks for AD, the mechanisms for its genesis, and how it might be prevented and treated.
Hillel Grossman, MD, expands the paradigm shift by focusing on diabetes mellitus and its relationship to AD. Early epidemiologic studies saw a seeming protective effect from AD among patients with diabetes mellitus. More recent prospective studies note that diabetes mellitus and insulin resistance seem to heighten the risk for AD. This finding has moved to the laboratory, where observations related to insulin-degrading enzyme and its role in amyloid metabolism suggest a potential mechanism for this heightened risk.