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Regional [18F]flortaucipir PET is more closely associated with disease severity than CSF p-tau in Alzheimer’s disease

Wolters, Emma E. ; Ossenkoppele, Rik LU ; Verfaillie, Sander C.J. ; Coomans, Emma M. ; Timmers, Tessa ; Visser, Denise ; Tuncel, Hayel ; Golla, Sandeep S.V. ; Windhorst, Albert D. and Boellaard, Ronald , et al. (2020) In European Journal of Nuclear Medicine and Molecular Imaging 47(12). p.2866-2878
Abstract

Purpose: In vivo Alzheimer’s disease (AD) biomarkers for tau pathology are cerebrospinal fluid (CSF) phosphorylated tau (p-tau) and [18F]flortaucipir positron emission tomography (PET). Our aim was to assess associations between CSF p-tau with [18F]flortaucipir PET and the associations of both tau biomarkers with cognition and atrophy. Methods: We included 78 amyloid positive cognitively impaired patients (clinical diagnoses mild cognitive impairment (MCI, n = 8) and AD dementia (n = 45) and 25 cognitively normal subjects with subjective cognitive decline (SCD) (40% amyloid-positive)). Dynamic 130 min [18F]flortaucipir PET scans were acquired to generate binding potential (BPND) images using... (More)

Purpose: In vivo Alzheimer’s disease (AD) biomarkers for tau pathology are cerebrospinal fluid (CSF) phosphorylated tau (p-tau) and [18F]flortaucipir positron emission tomography (PET). Our aim was to assess associations between CSF p-tau with [18F]flortaucipir PET and the associations of both tau biomarkers with cognition and atrophy. Methods: We included 78 amyloid positive cognitively impaired patients (clinical diagnoses mild cognitive impairment (MCI, n = 8) and AD dementia (n = 45) and 25 cognitively normal subjects with subjective cognitive decline (SCD) (40% amyloid-positive)). Dynamic 130 min [18F]flortaucipir PET scans were acquired to generate binding potential (BPND) images using receptor parametric mapping and standardized uptake values ratios of 80–100 min (SUVr80-100min) post injection. We obtained regional BPND and SUVr from entorhinal, limbic, and neocortical regions-of-interest (ROIs), closely aligning to the neuropathological tau staging schemes. Cognition was assessed using MMSE and composite scores of four cognitive domains, and atrophy was measured using gray matter volume covering the major brain lobes. First, we used linear regressions to investigate associations between CSF p-tau (independent variable) and tau PET (dependent variable). Second, we used linear regressions to investigate associations between CSF p-tau, tau PET (separate independent variables, model 1), and cognition (dependent variable). We then assessed the independent effects of CSF p-tau and tau PET on cognition by simultaneously adding the other tau biomarker as a predictor (model 2). Finally, we performed the same procedure for model 1 and 2, but replaced cognition with atrophy. Models were adjusted for age, sex, time lag between assessments, education (cognition only), and total intracranial volume (atrophy only). Results: Higher [18F]flortaucipir BPND was associated with higher CSF p-tau (range of standardized betas (sβ) across ROIs, 0.43–0.46; all p < 0.01). [18F]flortaucipir BPND was more strongly associated with cognition and atrophy than CSF p-tau. When [18F]flortaucipir BPND and CSF p-tau were entered simultaneously, [18F]flortaucipir BPND (range sβ = − 0.20 to – 0.57, all p < 0.05) was strongly associated with multiple cognitive domains and atrophy regions. SUVr showed comparable results to BPND. Conclusion: Regional [18F]flortaucipir BPND correlated stronger with cognition and neurodegeneration than CSF p-tau, suggesting that tau PET more accurately reflects disease severity in AD.

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Contribution to journal
publication status
published
subject
keywords
Atrophy, Cognition, CSF, PET, Tau, [F]flortaucipir
in
European Journal of Nuclear Medicine and Molecular Imaging
volume
47
issue
12
pages
13 pages
publisher
Springer
external identifiers
  • scopus:85083778058
  • pmid:32291510
ISSN
1619-7070
DOI
10.1007/s00259-020-04758-2
language
English
LU publication?
yes
id
0d4976e5-184b-4235-9082-44d4c796567e
date added to LUP
2020-05-28 17:24:42
date last changed
2021-01-17 06:21:59
@article{0d4976e5-184b-4235-9082-44d4c796567e,
  abstract     = {<p>Purpose: In vivo Alzheimer’s disease (AD) biomarkers for tau pathology are cerebrospinal fluid (CSF) phosphorylated tau (p-tau) and [<sup>18</sup>F]flortaucipir positron emission tomography (PET). Our aim was to assess associations between CSF p-tau with [<sup>18</sup>F]flortaucipir PET and the associations of both tau biomarkers with cognition and atrophy. Methods: We included 78 amyloid positive cognitively impaired patients (clinical diagnoses mild cognitive impairment (MCI, n = 8) and AD dementia (n = 45) and 25 cognitively normal subjects with subjective cognitive decline (SCD) (40% amyloid-positive)). Dynamic 130 min [<sup>18</sup>F]flortaucipir PET scans were acquired to generate binding potential (BP<sub>ND</sub>) images using receptor parametric mapping and standardized uptake values ratios of 80–100 min (SUVr<sub>80-100min</sub>) post injection. We obtained regional BP<sub>ND</sub> and SUVr from entorhinal, limbic, and neocortical regions-of-interest (ROIs), closely aligning to the neuropathological tau staging schemes. Cognition was assessed using MMSE and composite scores of four cognitive domains, and atrophy was measured using gray matter volume covering the major brain lobes. First, we used linear regressions to investigate associations between CSF p-tau (independent variable) and tau PET (dependent variable). Second, we used linear regressions to investigate associations between CSF p-tau, tau PET (separate independent variables, model 1), and cognition (dependent variable). We then assessed the independent effects of CSF p-tau and tau PET on cognition by simultaneously adding the other tau biomarker as a predictor (model 2). Finally, we performed the same procedure for model 1 and 2, but replaced cognition with atrophy. Models were adjusted for age, sex, time lag between assessments, education (cognition only), and total intracranial volume (atrophy only). Results: Higher [<sup>18</sup>F]flortaucipir BP<sub>ND</sub> was associated with higher CSF p-tau (range of standardized betas (sβ) across ROIs, 0.43–0.46; all p &lt; 0.01). [<sup>18</sup>F]flortaucipir BP<sub>ND</sub> was more strongly associated with cognition and atrophy than CSF p-tau. When [<sup>18</sup>F]flortaucipir BP<sub>ND</sub> and CSF p-tau were entered simultaneously, [<sup>18</sup>F]flortaucipir BP<sub>ND</sub> (range sβ = − 0.20 to – 0.57, all p &lt; 0.05) was strongly associated with multiple cognitive domains and atrophy regions. SUVr showed comparable results to BP<sub>ND</sub>. Conclusion: Regional [<sup>18</sup>F]flortaucipir BP<sub>ND</sub> correlated stronger with cognition and neurodegeneration than CSF p-tau, suggesting that tau PET more accurately reflects disease severity in AD.</p>},
  author       = {Wolters, Emma E. and Ossenkoppele, Rik and Verfaillie, Sander C.J. and Coomans, Emma M. and Timmers, Tessa and Visser, Denise and Tuncel, Hayel and Golla, Sandeep S.V. and Windhorst, Albert D. and Boellaard, Ronald and van der Flier, Wiesje M. and Teunissen, Charlotte E. and Scheltens, Philip and van Berckel, Bart N.M.},
  issn         = {1619-7070},
  language     = {eng},
  number       = {12},
  pages        = {2866--2878},
  publisher    = {Springer},
  series       = {European Journal of Nuclear Medicine and Molecular Imaging},
  title        = {Regional [<sup>18</sup>F]flortaucipir PET is more closely associated with disease severity than CSF p-tau in Alzheimer’s disease},
  url          = {http://dx.doi.org/10.1007/s00259-020-04758-2},
  doi          = {10.1007/s00259-020-04758-2},
  volume       = {47},
  year         = {2020},
}