Was Alois Alzheimer Right or Wrong?

Alois Alzheimer

© National Library of Medicine

In 1907, Aloysius "Alois" Alzheimer presented a rare case of dementia in a 51-year-old woman. This "presenile dementia" (younger than 60) was thought distinct enough from "senile dementia" (older than 65) to warrant a new name, thus it became known as, "Alzheimer's disease" (AD).

In the 1970s, however, some researchers argued that because of their similar symptoms and diagnostic hallmarks, "Alzheimer disease and senile dementia should be considered a single disease." ¹ This would mean that Alzheimer was wrong. Since then, AD research has been directed at finding a pathogenic cause, be it genetic, metabolic, toxic, or some other causative factor. But after 30 years, while the cause for presenile dementia, or early-onset familial AD, has been essentially found in the form of three mutant genes, the cause for senile dementia, or late-onset sporadic AD, remains unknown. ² Perhaps Alzheimer was right, after all.

Consider other diseases with onset at both middle age and old age. Senile hearing loss, for example, would be etiologically different from hearing loss in middle age despite similar symptoms and pathology - just as a new car that breaks down must have some mechanical defect, whereas problems with a very old car will be less obvious. Many other old-age diseases - osteoporosis, atherosclerosis, cataracts, and muscle atrophy - can also occur in young and middle aged individuals, but only in rare cases, generally the result of genetic defects. Thus, it appears to be a general case that the senile disorders constitute a family of illnesses that are fundamentally distinctive from their similar mid-age counterparts by origins, onset age, and prevalence - similar to our two types of car breakdown. Clearly, lumping them together while ignoring these distinctions would result in far-reaching confusions in research, a concern of a growing number of investigators. ^2-5

Emphasizing its age-related nature, however, does not mean that senile dementia would be hopeless and inevitable, because the disorder is largely influenced by genotypic difference such as ApoE genes and other contributing elements including diet, lifestyle, and social factors. As such, targeting these elements has proven effective in postponing, ameliorating, or preventing illnesses within one's lifespan. Nevertheless, because these elements are numerous, senile dementia is a multifactorial disorder and, as such, it should not surprise that there may not be any single factor that can be taken as its pathogenic cause.

Thus, defining senile dementia as AD has not just given it a new name, like amyotrophic lateral sclerosis for Lou Gehrig disease but has converted it conceptually into a reversible disease. While successfully arousing support from the public and Congress in hopes of a cure, this definition has singled senile dementia from other senile conditions and misguided its research toward pathogen-hunting. This may be why after 30 years of study and more than 60,000 papers published, the origins of senile dementia remain an enigma.

Current funding priorities should be restructured to emphasize research on senile dementia. Such studies should take aging, or passage of time, as the starting point for reasoning, and explain the hallmark lesions mechanistically and coherently. Studies should focus on the risk-enhancing factors, which seem to matter little for the young, but can push the oldest cells over the brink, and develop remedies that can activate and strengthen the cells to extend their lifespan - similar to what we do for other late-life disorders. Though much more challenging than tackling early-onset dementia, only such studies and the incremental progress that follows will answer the social crisis we face.

Ming Chen is director of the Neurobiology of Aging Research Laboratory at Bay Pines VA Medical Center and the University of South Florida.