NIA-AA staging of preclinical Alzheimer disease: discordance and concordance of CSF and imaging biomarkers.
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.
Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands. Electronic address: s.vos@maastrichtuniversity.nl.
Stephanie J B
SJB
Vos
Department of Radiology, Washington University School of Medicine, Saint Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA.
Brian A
BA
Gordon
Department of Radiology, Washington University School of Medicine, Saint Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA.
Yi
Y
Su
Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands; Department of Neurology, Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
Pieter Jelle
PJ
Visser
Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA; Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO, USA.
David M
DM
Holtzman
Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA; Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO, USA; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA.
John C
JC
Morris
Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA; Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO, USA.
Anne M
AM
Fagan
Department of Radiology, Washington University School of Medicine, Saint Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO, USA; Department of Neurological Surgery, Washington University School of Medicine, Saint Louis, MO, USA. Electronic address: benzingert@wustl.edu.
Tammie L S
TLS
Benzinger
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000000981:diagnostic imaging* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D049268:Positron-Emission Tomography; D012720:Severity of Illness Index
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
Aging; Alzheimer's disease; Amyloid; Biomarkers; Cerebrospinal fluid; Comorbidities; Diagnosis; MRI; Neuroimaging; Neuronal injury; PET; Prognosis