NIA-AA staging of preclinical Alzheimer disease: discordance and concordance of CSF and imaging biomarkers

Stephanie J. B. Vos*, Brian A. Gordon, Yi Su, Pieter Jelle Visser, David M. Holtzman, John C. Morris, Anne M. Fagan, Tammie L. S. Benzinger*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


The National Institute of Aging and Alzheimer's Association (NIA-AA) criteria for Alzheimer disease (AD) treat neuroimaging and cerebrospinal fluid (CSF) markers of AD pathology as if they would be interchangeable. We tested this assumption in 212 cognitively normal participants who have both neuroimaging and CSF measures of beta-amyloid (CSF A beta(1-42) and positron emission tomography imaging with Pittsburgh Compound B) and neuronal injury (CSF t-tau and p-tau and structural magnetic resonance imaging) with longitudinal clinical follow-up. Participants were classified in preclinical AD stage 1 (beta-amyloidosis) or preclinical AD stage 2+ (beta-amyloidosis and neuronal injury) using the NIA-AA criteria, or in the normal or suspected non-Alzheimer disease pathophysiology group (neuronal injury without beta-amyloidosis). At baseline, 21% of participants had preclinical AD based on CSF and 28% based on neuroimaging. Between modalities, staging was concordant in only 47% of participants. Disagreement resulted from low concordance between biomarkers of neuronal injury. Still, individuals in stage 2+ using either criterion had an increased risk for clinical decline. This highlights the heterogeneity of the definition of neuronal injury and has important implications for clinical trials using biomarkers for enrollment or as surrogate end point measures.
Original languageEnglish
Pages (from-to)1-8
JournalNeurobiology of Aging
Publication statusPublished - Aug 2016


  • Alzheimer's disease
  • Amyloid
  • Neuronal injury
  • Cerebrospinal fluid
  • Neuroimaging
  • Comorbidities
  • Aging
  • Diagnosis
  • Prognosis
  • Biomarkers
  • PET
  • MRI

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