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Comparing ATN-T designation by tau PET visual reads, tau PET quantification, and CSF PTau181 across three cohorts

Provost, Karine ; Iaccarino, Leonardo ; Soleimani-Meigooni, David N. ; Baker, Suzanne ; Edwards, Lauren ; Eichenlaub, Udo ; Hansson, Oskar LU orcid ; Jagust, William ; Janabi, Mustafa and La Joie, Renaud , et al. (2021) In European Journal of Nuclear Medicine and Molecular Imaging 48(7). p.2259-2271
Abstract

Purpose: To compare rates of tau biomarker positivity (T-status) per the 2018 Alzheimer’s Disease (AD) Research Framework derived from [18F]flortaucipir (FTP) PET visual assessment, FTP quantification, and cerebrospinal fluid (CSF) phosphorylated Tau-181 (PTau181). Methods: We included 351 subjects with varying clinical diagnoses from three cohorts with available FTP PET and CSF PTau181 within 18 months. T-status was derived from (1) FTP visual assessment by two blinded raters; (2) FTP standardized uptake value ratio (SUVR) quantification from a temporal meta-ROI (threshold: SUVR ≥1.27); and (3) Elecsys® Phospho-Tau (181P) CSF (Roche Diagnostics) concentrations (threshold: PTau181 ≥ 24.5 pg/mL). Results: FTP visual reads... (More)

Purpose: To compare rates of tau biomarker positivity (T-status) per the 2018 Alzheimer’s Disease (AD) Research Framework derived from [18F]flortaucipir (FTP) PET visual assessment, FTP quantification, and cerebrospinal fluid (CSF) phosphorylated Tau-181 (PTau181). Methods: We included 351 subjects with varying clinical diagnoses from three cohorts with available FTP PET and CSF PTau181 within 18 months. T-status was derived from (1) FTP visual assessment by two blinded raters; (2) FTP standardized uptake value ratio (SUVR) quantification from a temporal meta-ROI (threshold: SUVR ≥1.27); and (3) Elecsys® Phospho-Tau (181P) CSF (Roche Diagnostics) concentrations (threshold: PTau181 ≥ 24.5 pg/mL). Results: FTP visual reads yielded the highest rates of T+, while T+ by SUVR increased progressively from cognitively normal (CN) through mild cognitive impairment (MCI) and AD dementia. T+ designation by CSF PTau181 was intermediate between FTP visual reads and SUVR values in CN, similar to SUVR in MCI, and lower in AD dementia. Concordance in T-status between modality pairs ranged from 68 to 76% and varied by clinical diagnosis, being highest in patients with AD dementia. In discriminating Aβ + MCI and AD subjects from healthy controls and non-AD participants, FTP visual assessment was most sensitive (0.96) but least specific (0.60). Specificity was highest with FTP SUVR (0.91) with sensitivity of 0.89. Sensitivity (0.73) and specificity (0.72) were balanced for PTau181. Conclusion: The choice of tau biomarker may differ by disease stage and research goals that seek to maximize sensitivity or specificity. Visual interpretations of tau PET enhance sensitivity compared to quantification alone, particularly in early disease stages.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, Biomarkers, CSF, Flortaucipir, PET, Tau
in
European Journal of Nuclear Medicine and Molecular Imaging
volume
48
issue
7
pages
13 pages
publisher
Springer
external identifiers
  • scopus:85098793440
  • pmid:33398408
ISSN
1619-7070
DOI
10.1007/s00259-020-05152-8
language
English
LU publication?
yes
id
ddca0f01-6f18-4a61-8e50-491228956342
date added to LUP
2021-01-14 09:32:33
date last changed
2024-06-13 05:03:14
@article{ddca0f01-6f18-4a61-8e50-491228956342,
  abstract     = {{<p>Purpose: To compare rates of tau biomarker positivity (T-status) per the 2018 Alzheimer’s Disease (AD) Research Framework derived from [<sup>18</sup>F]flortaucipir (FTP) PET visual assessment, FTP quantification, and cerebrospinal fluid (CSF) phosphorylated Tau-181 (PTau181). Methods: We included 351 subjects with varying clinical diagnoses from three cohorts with available FTP PET and CSF PTau181 within 18 months. T-status was derived from (1) FTP visual assessment by two blinded raters; (2) FTP standardized uptake value ratio (SUVR) quantification from a temporal meta-ROI (threshold: SUVR ≥1.27); and (3) Elecsys® Phospho-Tau (181P) CSF (Roche Diagnostics) concentrations (threshold: PTau181 ≥ 24.5 pg/mL). Results: FTP visual reads yielded the highest rates of T+, while T+ by SUVR increased progressively from cognitively normal (CN) through mild cognitive impairment (MCI) and AD dementia. T+ designation by CSF PTau181 was intermediate between FTP visual reads and SUVR values in CN, similar to SUVR in MCI, and lower in AD dementia. Concordance in T-status between modality pairs ranged from 68 to 76% and varied by clinical diagnosis, being highest in patients with AD dementia. In discriminating Aβ + MCI and AD subjects from healthy controls and non-AD participants, FTP visual assessment was most sensitive (0.96) but least specific (0.60). Specificity was highest with FTP SUVR (0.91) with sensitivity of 0.89. Sensitivity (0.73) and specificity (0.72) were balanced for PTau181. Conclusion: The choice of tau biomarker may differ by disease stage and research goals that seek to maximize sensitivity or specificity. Visual interpretations of tau PET enhance sensitivity compared to quantification alone, particularly in early disease stages.</p>}},
  author       = {{Provost, Karine and Iaccarino, Leonardo and Soleimani-Meigooni, David N. and Baker, Suzanne and Edwards, Lauren and Eichenlaub, Udo and Hansson, Oskar and Jagust, William and Janabi, Mustafa and La Joie, Renaud and Lesman-Segev, Orit and Mellinger, Taylor J. and Miller, Bruce L. and Ossenkoppele, Rik and Pham, Julie and Smith, Ruben and Sonni, Ida and Strom, Amelia and Mattsson-Carlgren, Niklas and Rabinovici, Gil D.}},
  issn         = {{1619-7070}},
  keywords     = {{Alzheimer’s disease; Biomarkers; CSF; Flortaucipir; PET; Tau}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  pages        = {{2259--2271}},
  publisher    = {{Springer}},
  series       = {{European Journal of Nuclear Medicine and Molecular Imaging}},
  title        = {{Comparing ATN-T designation by tau PET visual reads, tau PET quantification, and CSF PTau181 across three cohorts}},
  url          = {{http://dx.doi.org/10.1007/s00259-020-05152-8}},
  doi          = {{10.1007/s00259-020-05152-8}},
  volume       = {{48}},
  year         = {{2021}},
}