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Discordant amyloid-...
Discordant amyloid-β PET and CSF biomarkers and its clinical consequences
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- De Wilde, Arno (author)
- Vrije Universiteit Amsterdam
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- Reimand, Juhan (author)
- Vrije Universiteit Amsterdam,North Estonia Medical Centre,Tallinn University of Technology
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- Teunissen, Charlotte E. (author)
- Vrije Universiteit Amsterdam
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- Zwan, Marissa (author)
- Vrije Universiteit Amsterdam
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- Windhorst, Albert D. (author)
- Vrije Universiteit Amsterdam
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- Boellaard, Ronald (author)
- Vrije Universiteit Amsterdam
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- Van Der Flier, Wiesje M. (author)
- Vrije Universiteit Amsterdam
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- Scheltens, Philip (author)
- Vrije Universiteit Amsterdam
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- Van Berckel, Bart N.M. (author)
- Vrije Universiteit Amsterdam
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- Bouwman, Femke (author)
- Vrije Universiteit Amsterdam
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- Ossenkoppele, Rik (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Vrije Universiteit Amsterdam
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(creator_code:org_t)
- 2019-09-12
- 2019
- English.
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In: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 11
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Abstract
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- Background: In 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. Methods: We 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. Results: We 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 (P interaction = 0.19), while these scores declined in concordant-positive (β - 0.75[0.08] patients (P interaction < 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. Conclusions: Discordant 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- Alzheimer's disease
- Amyloid
- Cerebrospinal fluid
- Dementia
- Mild cognitive impairment
- Positron emission tomography
- Subjective cognitive decline
Publication and Content Type
- art (subject category)
- ref (subject category)
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De Wilde, Arno
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Reimand, Juhan
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Teunissen, Charl ...
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Zwan, Marissa
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Windhorst, Alber ...
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Boellaard, Ronal ...
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Van Der Flier, W ...
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Scheltens, Phili ...
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Van Berckel, Bar ...
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Bouwman, Femke
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Ossenkoppele, Ri ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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Alzheimer's Rese ...
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Lund University