NIA-AA staging of preclinical Alzheimer disease: discordance and concordance of CSF and imaging biomarkers
Open accessAbstract
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 β-amyloid (CSF Aβ1-42 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 (β-amyloidosis) or preclinical AD stage 2+ (β-amyloidosis and neuronal injury) using the NIA-AA criteria, or in the normal or suspected non-Alzheimer disease pathophysiology group (neuronal injury without β-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.
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Discordances between imaging and CSF biomarkers may occur.
“Discordances between imaging and CSF biomarkers may occur [36,41,116–119].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [36]
The correlation between CSF T-tau and P-tau is typically much higher than between CSF T-tau and MRI measures of atrophy or FDG PET.
“CSF levels of T-tau and P-tau are tightly correlated within cohorts of AD patients and controls [145], and the correlation between CSF T-tau and P-tau is typically much higher than between CSF T-tau and MRI measures of atrophy or FDG PET [36,115].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [36]
Differences among (N) biomarkers may result in discordances.
“These differences may result in discordances [36,43,115,119,159].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [36]
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- Authors
- Vos, S. J. B., Gordon, B. A., Su, Y., Visser, P. J., Holtzman, D. M., Morris, J. C., Fagan, A. M., & Benzinger, T. L. S.
- Affiliations
- Maastricht University (NL)
- Washington University in St. Louis (US)
- Corresponding author
- Vos, Stephanie J.B.
- Benzinger, Tammie L.S.
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 44
- Pages
- 1-8
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC4913039
- OpenAlex
- W2321587642
- Cited by
- 98
- References
- 10
- Citations by year
- 2025: 5 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 17 · 2020: 15 · 2019: 8 · 2018: 20 · 2017: 15 · 2016: 3
- FWCI
- 13.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Innovative Medicines Initiative (115372)
- Seventh Framework Programme
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- preclinical Alzheimer's disease, NIA-AA criteria, cerebrospinal fluid biomarkers, neuroimaging biomarkers, amyloid-beta, tau protein, Pittsburgh compound B, CSF tau, structural MRI, biomarker concordance, cognitive decline risk, surrogate endpoints, clinical trial recruitment
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Peptide Fragments, Severity of Illness Index, Biomarkers, Amyloid beta-Peptides, Positron-Emission Tomography, Neuroimaging
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