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Discordant amyloid-β PET and CSF biomarkers and its clinical consequences

Authors
  • de Wilde, Arno1
  • Reimand, Juhan1, 2, 3
  • Teunissen, Charlotte E.4
  • Zwan, Marissa1
  • Windhorst, Albert D.5
  • Boellaard, Ronald5
  • van der Flier, Wiesje M.1, 6
  • Scheltens, Philip1
  • van Berckel, Bart N. M.5
  • Bouwman, Femke1
  • Ossenkoppele, Rik1, 7
  • 1 Vrije Universiteit Amsterdam, Amsterdam UMC, Department of Neurology & Alzheimer Center, Amsterdam Neuroscience, P.O. Box 7057, Amsterdam, 1007 MB, The Netherlands , Amsterdam (Netherlands)
  • 2 Tallinn University of Technology, Department of Health Technologies, Tallinn, Estonia , Tallinn (Estonia)
  • 3 North Estonia Medical Centre, Center of Radiology, Tallinn, Estonia , Tallinn (Estonia)
  • 4 Vrije Universiteit Amsterdam, Amsterdam UMC, Neurochemistry laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam, The Netherlands , Amsterdam (Netherlands)
  • 5 Vrije Universiteit Amsterdam, Amsterdam UMC, Department of Radiology & Nuclear Medicine, Amsterdam Neuroscience, Amsterdam, The Netherlands , Amsterdam (Netherlands)
  • 6 Vrije Universiteit Amsterdam, Amsterdam UMC, Department of Epidemiology & Biostatistics, Amsterdam Neuroscience, Amsterdam, The Netherlands , Amsterdam (Netherlands)
  • 7 Lund University, Clinical Memory Research Unit, Malmö, Sweden , Malmö (Sweden)
Type
Published Article
Journal
Alzheimer's Research & Therapy
Publisher
BioMed Central
Publication Date
Sep 12, 2019
Volume
11
Issue
1
Identifiers
DOI: 10.1186/s13195-019-0532-x
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundIn vivo, high cerebral amyloid-β load has been associated with (i) reduced concentrations of Aβ42 in cerebrospinal fluid and (ii) increased retention using amyloid-β positron emission tomography. Although these two amyloid-β biomarkers generally show good correspondence, ~ 10–20% of cases have discordant results. To assess the consequences of having discordant amyloid-β PET and CSF biomarkers on clinical features, biomarkers, and longitudinal cognitive trajectories.MethodsWe included 768 patients (194 with subjective cognitive decline (SCD), 127 mild cognitive impairment (MCI), 309 Alzheimer’s dementia (AD), and 138 non-AD) who were categorized as concordant-negative (n = 315, 41%), discordant (n = 97, 13%), or concordant-positive (n = 356, 46%) based on CSF and PET results. We compared discordant with both concordant-negative and concordant-positive groups on demographics, clinical syndrome, apolipoprotein E (APOE) ε4 status, CSF tau, and clinical and neuropsychological progression.ResultsWe found an increase from concordant-negative to discordant to concordant-positive in rates of APOE ε4 (28%, 55%, 70%, Z = − 10.6, P < 0.001), CSF total tau (25%, 45%, 78%, Z = − 13.7, P < 0.001), and phosphorylated tau (28%, 43%, 80%, Z = − 13.7, P < 0.001) positivity. In patients without dementia, linear mixed models showed that Mini-Mental State Examination and memory composite scores did not differ between concordant-negative (β [SE] − 0.13[0.08], P = 0.09) and discordant (β 0.08[0.15], P = 0.15) patients (Pinteraction = 0.19), while these scores declined in concordant-positive (β − 0.75[0.08] patients (Pinteraction < 0.001). In patients with dementia, longitudinal cognitive scores were not affected by amyloid-β biomarker concordance or discordance. Clinical progression rates from SCD to MCI or dementia (P = 0.01) and from MCI to dementia (P = 0.003) increased from concordant-negative to discordant to concordant-positive.ConclusionsDiscordant cases were intermediate to concordant-negative and concordant-positive patients in terms of genetic (APOE ε4) and CSF (tau) markers of AD. While biomarker agreement did not impact cognition in patients with dementia, discordant biomarkers are not benign in patients without dementia given their higher risk of clinical progression.

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