A brief history of "Alzheimer disease": Multiple meanings separated by a common name

Abstract

The field of Alzheimer disease (AD) has a nosologic problem: The diagnostic label "Alzheimer disease" has several distinctive meanings. The term probable AD was introduced in 1984 to designate a clinically diagnosed acquired and progressive amnestic dementia for which there was no evidence for another etiology. Probable AD represented a clinicopathologic entity that assumed a specific and sensitive linkage between amnestic dementia and the neuropathology of β-amyloid-containing neuritic plaques and tau-containing neurofibrillary tangles. The clinicopathologic model represented by probable AD was adapted in abbreviated form for population-based studies and general clinical practice, although the uncertainty connoted by "probable" was often overlooked. Representing the growing public awareness of later life cognitive impairment, a vernacular meaning of AD arose out of the clinicopathologic model in which AD represented all dementia not due to another clinically apparent cause. In contrast, by the 1990s, neuropathologists settled on a definition of AD based entirely on a sufficient burden of neuritic plaques and neurofibrillary tangles at postmortem examination, regardless of antemortem clinical status. In the last decade, the availability of fluid and imaging biomarkers that measure β-amyloid and tau abnormalities has enabled antemortem pathobiological diagnoses, highlighting the divide between the clinicopathologic model, the vernacular usage, and the pathobiological models. Each definition has value. However, the meanings of AD as defined by each of these models are not interchangeable. The pathobiological one is the only one that is unambiguous.

Figure. Unique patient diagnoses of “Alzheimer disease” in persons in Olmsted County, Minnesota, from 1980 to 2014

We used the Rochester Epidemiology Project resources to identify persons aged ≥65 years with an International Classification of Disease (ICD-8) or Hospital Adaptation of the ICD, 2nd edition (HICDA) diagnostic code for “Alzheimer disease.” The term “Alzheimer disease” was introduced into the HICDA system only in 1975. The x-axis represents the year, and the y-axis the number of unique persons assigned in that year with a diagnosis of “Alzheimer disease.”