Posted 9 April 2007

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How Early-onset Dementia Led to a Historic Discovery

When Alois Alzheimer described the case of Auguste D. to an audience of fellow psychiatrists in Tuebingen, Germany, in 1906, what set her case apart was the fact that her dementia appeared before she was 50 years old. Dementia at a more advanced age was considered part of normal aging. But this relatively young German hausfrau's increasingly disruptive behavior caused her distraught husband to bring her in for a doctor's examination when she was 51. It fell upon Dr. Alzheimer to follow her case. Alzheimer's mentor Emil Kraepelin of Munich, the foremost psychiatrist in his day, promoted the fundamental insight that dementia is a physical, organic disease of the brain, so when Auguste D. died, Alzheimer examined her brain for unusual pathology. At the time, based on the contemporary theories of Freud, psychotic or "crazy" behavior was thought to result from psychodynamic causes, so Alzheimer's discovery of plaques and tangles in Auguste D.'s brain was a landmark (although his contemporaries were underwhelmed). The German medical literature of the time recognized that this mid-life dementia was more common in certain families, so the idea of familial Alzheimer disease goes back to those days, as well.

Until recent times, the term Alzheimer disease referred exclusively to cases where the disease expressed itself before the age of 65. Alzheimer and Kraepelin themselves had defined the disease in this way. Indeed Alzheimer believed that in older people, dementia was the result of atherosclerosis. For decades thereafter, most investigators distinguished Alzheimer disease as a rare mid-life affliction from garden-variety senility. This distinction was blurred by the fact that even within a family, the disease would develop across a range of ages, from 50 to 70.

In the 1960s, Sir Martin Roth, Bernard Tomlinson, and Gary Blessed reported that the pathology of plaques and tangles also occurred across middle to old age. But it was not until the 1970s that the New York pathologist Robert Katzman asserted that late-onset AD was no different from early-onset AD. "The brilliant contribution Katzman made was that the general decline of cognition and life function, as well as the pathology, follow a similar pattern in late-onset, early-onset, and familial AD," notes neurologist Daniel Pollen at the University of Massachusetts Medical Center in Worcester.

Since then, scientists have come to agree that the distinction between "presenile" and "senile" forms of AD dementia is obsolete. The early-onset and late-onset forms are now seen as a single disease. Alzheimer disease became a major public health issue in an aging society, and its occurrence in elderly people is what people typically mean today when they speak of Alzheimer disease. Indeed, in an ironic twist, almost no one thinks of AD as a disease that a younger person can get. The original form of Alzheimer disease has been largely forgotten, except by some researchers.—Gabrielle Strobel.