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“Alzheimer's disease” is neither “Alzheimer's clinical syndrome” nor “dementia”
Author(s) -
Jagust William,
Jack Clifford R.,
Bennett David A.,
Blennow Kaj,
Haeberlein Samantha Budd,
Holtzman David M.,
Jessen Frank,
Karlawish Jason,
Liu Enchi,
Molinuevo Jose Luis,
Montine Thomas,
Phelps Creighton,
Rankin Katherine P.,
Rowe Christopher C.,
Scheltens Philip,
Siemers Eric,
Sperling Reisa
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.11.002
Subject(s) - medicine , dementia , library science , gerontology , psychology , disease , pathology , computer science
In this issue of Alzheimer’s & Dementia, Sweeney et al. [1] propose to extend the recently published NIA-AA Research Framework [2] by incorporating measures of vascular dysfunction as putative AD biomarkers. Although we strongly agree with the importance of a wide range of vascular factors in the development of cognitive decline, the authors misunderstand a central issue addressed in the framework: the fundamental definition of Alzheimer’s disease (AD) and its distinction from the terms “Alzheimer’s clinical syndrome” and dementia. We propose these terms to distinguish between the pathological features of the disease and its clinical consequences. Although there is extensive evidence that vascular factors contribute to the Alzheimer’s clinical syndrome and dementia, the evidence that they contribute to AD pathological changes is limited. For decades, AD has been defined as a clinical dementia syndrome confirmed at autopsy by the neuropathological observation of neuritic plaques and neurofibrillary tangles, which are now known to be composed of b-amyloid and paired helical filament tau. This has most recently been codified in the 2012 NIA-Alzheimer’s Association guidelines for the neuropathologic evaluation of AD that define an approach to characterizing the plaque and tangle hallmark lesions [3]. These guidelines note the likely importance of other pathological findings to the clinical presentation and specifically suggest the measurement of a number of them including vascular brain injury, Lewy body disease, and TDP-43 inclusions. However, none of these pathologies is, or have ever been, required for the neuropathological diagnosis of AD, which for decades has been and remains entirely based on the density and distribution of neuritic plaques and neurofibrillary tangles. The neuropathologic guidelines accomplished two important goals: (1) they provided a clear measure for neuropathologists to define AD neuropathologic change and (2) they divorced the pathological diagnosis of AD from the clinical diagnosis. This latter point is crucial because the clinical features associated with the pathologic changes are highly variable, including multiple cognitive and behavioral syndromes along with the complete absence of symptoms. The NIA-AA research framework built on these neuropathologic advances now that we can detect amyloid and