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The impact of demographic, clinical, genetic, and imaging variables on tau PET status

Ossenkoppele, Rik LU ; Leuzy, Antoine LU ; Cho, Hanna ; Sudre, Carole H. ; Strandberg, Olof LU ; Smith, Ruben LU ; Palmqvist, Sebastian LU orcid ; Mattsson-Carlgren, Niklas LU orcid ; Olsson, Tomas and Jögi, Jonas LU orcid , et al. (2021) In European Journal of Nuclear Medicine and Molecular Imaging 48(7). p.2245-2258
Abstract

Purpose: A substantial proportion of amyloid-β (Aβ)+ patients with clinically diagnosed Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) are tau PET–negative, while some clinically diagnosed non-AD neurodegenerative disorder (non-AD) patients or cognitively unimpaired (CU) subjects are tau PET–positive. We investigated which demographic, clinical, genetic, and imaging variables contributed to tau PET status. Methods: We included 2338 participants (430 Aβ+ AD dementia, 381 Aβ+ MCI, 370 non-AD, and 1157 CU) who underwent [18F]flortaucipir (n = 1944) or [18F]RO948 (n = 719) PET. Tau PET positivity was determined in the entorhinal cortex, temporal meta-ROI, and Braak V-VI regions using previously... (More)

Purpose: A substantial proportion of amyloid-β (Aβ)+ patients with clinically diagnosed Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) are tau PET–negative, while some clinically diagnosed non-AD neurodegenerative disorder (non-AD) patients or cognitively unimpaired (CU) subjects are tau PET–positive. We investigated which demographic, clinical, genetic, and imaging variables contributed to tau PET status. Methods: We included 2338 participants (430 Aβ+ AD dementia, 381 Aβ+ MCI, 370 non-AD, and 1157 CU) who underwent [18F]flortaucipir (n = 1944) or [18F]RO948 (n = 719) PET. Tau PET positivity was determined in the entorhinal cortex, temporal meta-ROI, and Braak V-VI regions using previously established cutoffs. We performed bivariate binary logistic regression models with tau PET status (positive/negative) as dependent variable and age, sex, APOEε4, Aβ status (only in CU and non-AD analyses), MMSE, global white matter hyperintensities (WMH), and AD-signature cortical thickness as predictors. Additionally, we performed multivariable binary logistic regression models to account for all other predictors in the same model. Results: Tau PET positivity in the temporal meta-ROI was 88.6% for AD dementia, 46.5% for MCI, 9.5% for non-AD, and 6.1% for CU. Among Aβ+ participants with AD dementia and MCI, lower age, MMSE score, and AD-signature cortical thickness showed the strongest associations with tau PET positivity. In non-AD and CU participants, presence of Aβ was the strongest predictor of a positive tau PET scan. Conclusion: We identified several demographic, clinical, and neurobiological factors that are important to explain the variance in tau PET retention observed across the AD pathological continuum, non-AD neurodegenerative disorders, and cognitively unimpaired persons.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, Aβ, Dementia, MCI, PET, Tau
in
European Journal of Nuclear Medicine and Molecular Imaging
volume
48
issue
7
pages
14 pages
publisher
Springer
external identifiers
  • pmid:33215319
  • scopus:85096308018
ISSN
1619-7070
DOI
10.1007/s00259-020-05099-w
language
English
LU publication?
yes
id
be322093-45b8-4b8c-9336-2ad3b71f1040
date added to LUP
2020-12-02 12:44:10
date last changed
2024-04-17 19:56:52
@article{be322093-45b8-4b8c-9336-2ad3b71f1040,
  abstract     = {{<p>Purpose: A substantial proportion of amyloid-β (Aβ)+ patients with clinically diagnosed Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) are tau PET–negative, while some clinically diagnosed non-AD neurodegenerative disorder (non-AD) patients or cognitively unimpaired (CU) subjects are tau PET–positive. We investigated which demographic, clinical, genetic, and imaging variables contributed to tau PET status. Methods: We included 2338 participants (430 Aβ+ AD dementia, 381 Aβ+ MCI, 370 non-AD, and 1157 CU) who underwent [<sup>18</sup>F]flortaucipir (n = 1944) or [<sup>18</sup>F]RO948 (n = 719) PET. Tau PET positivity was determined in the entorhinal cortex, temporal meta-ROI, and Braak V-VI regions using previously established cutoffs. We performed bivariate binary logistic regression models with tau PET status (positive/negative) as dependent variable and age, sex, APOEε4, Aβ status (only in CU and non-AD analyses), MMSE, global white matter hyperintensities (WMH), and AD-signature cortical thickness as predictors. Additionally, we performed multivariable binary logistic regression models to account for all other predictors in the same model. Results: Tau PET positivity in the temporal meta-ROI was 88.6% for AD dementia, 46.5% for MCI, 9.5% for non-AD, and 6.1% for CU. Among Aβ+ participants with AD dementia and MCI, lower age, MMSE score, and AD-signature cortical thickness showed the strongest associations with tau PET positivity. In non-AD and CU participants, presence of Aβ was the strongest predictor of a positive tau PET scan. Conclusion: We identified several demographic, clinical, and neurobiological factors that are important to explain the variance in tau PET retention observed across the AD pathological continuum, non-AD neurodegenerative disorders, and cognitively unimpaired persons.</p>}},
  author       = {{Ossenkoppele, Rik and Leuzy, Antoine and Cho, Hanna and Sudre, Carole H. and Strandberg, Olof and Smith, Ruben and Palmqvist, Sebastian and Mattsson-Carlgren, Niklas and Olsson, Tomas and Jögi, Jonas and Stormrud, Erik and Ryu, Young Hoon and Choi, Jae Yong and Boxer, Adam L. and Gorno-Tempini, Maria L. and Miller, Bruce L. and Soleimani-Meigooni, David and Iaccarino, Leonardo and La Joie, Renaud and Borroni, Edilio and Klein, Gregory and Pontecorvo, Michael J. and Devous, Michael D. and Villeneuve, Sylvia and Lyoo, Chul Hyoung and Rabinovici, Gil D. and Hansson, Oskar}},
  issn         = {{1619-7070}},
  keywords     = {{Alzheimer’s disease; Aβ; Dementia; MCI; PET; Tau}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  pages        = {{2245--2258}},
  publisher    = {{Springer}},
  series       = {{European Journal of Nuclear Medicine and Molecular Imaging}},
  title        = {{The impact of demographic, clinical, genetic, and imaging variables on tau PET status}},
  url          = {{http://dx.doi.org/10.1007/s00259-020-05099-w}},
  doi          = {{10.1007/s00259-020-05099-w}},
  volume       = {{48}},
  year         = {{2021}},
}