Advanced

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

De Wilde, Arno ; Reimand, Juhan ; Teunissen, Charlotte E. ; Zwan, Marissa ; Windhorst, Albert D. ; Boellaard, Ronald ; Van Der Flier, Wiesje M. ; Scheltens, Philip ; Van Berckel, Bart N.M. and Bouwman, Femke , et al. (2019) In Alzheimer's Research and Therapy 11.
Abstract

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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, Amyloid, Cerebrospinal fluid, Dementia, Mild cognitive impairment, Positron emission tomography, Subjective cognitive decline
in
Alzheimer's Research and Therapy
volume
11
article number
78
publisher
BioMed Central
external identifiers
  • scopus:85072103935
  • pmid:31511058
ISSN
1758-9193
DOI
10.1186/s13195-019-0532-x
language
English
LU publication?
yes
id
f7d1f314-d809-4dc3-91a2-3811b042c0d8
date added to LUP
2019-10-01 11:44:19
date last changed
2019-11-25 09:34:55
@article{f7d1f314-d809-4dc3-91a2-3811b042c0d8,
  abstract     = {<p>Background: In vivo, high cerebral amyloid-β load has been associated with (i) reduced concentrations of Aβ<sub>42</sub> 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 &lt; 0.001), CSF total tau (25%, 45%, 78%, Z = - 13.7, P &lt; 0.001), and phosphorylated tau (28%, 43%, 80%, Z = - 13.7, P &lt; 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 <sub>interaction</sub> = 0.19), while these scores declined in concordant-positive (β - 0.75[0.08] patients (P <sub>interaction</sub> &lt; 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.</p>},
  author       = {De Wilde, Arno and Reimand, Juhan and Teunissen, Charlotte E. and Zwan, Marissa and Windhorst, Albert D. and Boellaard, Ronald and Van Der Flier, Wiesje M. and Scheltens, Philip and Van Berckel, Bart N.M. and Bouwman, Femke and Ossenkoppele, Rik},
  issn         = {1758-9193},
  language     = {eng},
  month        = {09},
  publisher    = {BioMed Central},
  series       = {Alzheimer's Research and Therapy},
  title        = {Discordant amyloid-β PET and CSF biomarkers and its clinical consequences},
  url          = {http://dx.doi.org/10.1186/s13195-019-0532-x},
  doi          = {10.1186/s13195-019-0532-x},
  volume       = {11},
  year         = {2019},
}