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Perspective: Clinical relevance of the dichotomous classification of Alzheimer's disease biomarkers: Should there be a “gray zone”?
Author(s) -
McRaeMcKee Kevin,
UdehMomoh Chinedu T.,
Price Geraint,
Bajaj Sumali,
Jager Celeste A.,
Scott David,
Hadjichrysanthou Christoforos,
McNaughton Emily,
Bracoud Luc,
AhmadiAbhari Sara,
Wolf Frank,
Anderson Roy M.,
Middleton Lefkos T.
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.2019.07.010
Subject(s) - disease , alzheimer's disease , neuroimaging , alzheimer's disease neuroimaging initiative , psychology , perspective (graphical) , biomarker , clinical trial , neuroscience , medicine , cognitive psychology , pathology , artificial intelligence , biology , computer science , biochemistry
The 2018 National Institute on Aging and the Alzheimer's Association (NIA‐AA) research framework recently redefined Alzheimer's disease (AD) as a biological construct, based on in vivo biomarkers reflecting key neuropathologic features. Combinations of normal/abnormal levels of three biomarker categories, based on single thresholds, form the AD signature profile that defines the biological disease state as a continuum, independent of clinical symptomatology. While single thresholds may be useful in defining the biological signature profile, we provide evidence that their use in studies with cognitive outcomes merits further consideration. Using data from the Alzheimer's Disease Neuroimaging Initiative with a focus on cortical amyloid binding, we discuss the limitations of applying the biological definition of disease status as a tool to define the increased likelihood of the onset of the Alzheimer's clinical syndrome and the effects that this may have on trial study design. We also suggest potential research objectives going forward and what the related data requirements would be.