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Tau pathology and relative cerebral blood flow are independently associated with cognition in Alzheimer’s disease

Visser, Denise ; Wolters, Emma E. ; Verfaillie, Sander C.J. ; Coomans, Emma M. ; Timmers, Tessa ; Tuncel, Hayel ; Reimand, Juhan ; Boellaard, Ronald ; Windhorst, Albert D. and Scheltens, Philip , et al. (2020) In European Journal of Nuclear Medicine and Molecular Imaging 47(13). p.3165-3175
Abstract

Purpose: We aimed to investigate associations between tau pathology and relative cerebral blood flow (rCBF), and their relationship with cognition in Alzheimer’s disease (AD), by using a single dynamic [18F]flortaucipir positron emission tomography (PET) scan. Methods: Seventy-one subjects with AD (66 ± 8 years, mini-mental state examination (MMSE) 23 ± 4) underwent a dynamic 130-min [18F]flortaucipir PET scan. Cognitive assessment consisted of composite scores of four cognitive domains. For tau pathology and rCBF, receptor parametric mapping (cerebellar gray matter reference region) was used to create uncorrected and partial volume-corrected parametric images of non-displaceable binding potential (BPND)... (More)

Purpose: We aimed to investigate associations between tau pathology and relative cerebral blood flow (rCBF), and their relationship with cognition in Alzheimer’s disease (AD), by using a single dynamic [18F]flortaucipir positron emission tomography (PET) scan. Methods: Seventy-one subjects with AD (66 ± 8 years, mini-mental state examination (MMSE) 23 ± 4) underwent a dynamic 130-min [18F]flortaucipir PET scan. Cognitive assessment consisted of composite scores of four cognitive domains. For tau pathology and rCBF, receptor parametric mapping (cerebellar gray matter reference region) was used to create uncorrected and partial volume-corrected parametric images of non-displaceable binding potential (BPND) and R1, respectively. (Voxel-wise) linear regressions were used to investigate associations between BPND and/or R1 and cognition. Results: Higher [18F]flortaucipir BPND was associated with lower R1 in the lateral temporal, parietal and occipital regions. Higher medial temporal BPND was associated with worse memory, and higher lateral temporal BPND with worse executive functioning and language. Higher parietal BPND was associated with worse executive functioning, language and attention, and higher occipital BPND with lower cognitive scores across all domains. Higher frontal BPND was associated with worse executive function and attention. For [18F]flortaucipir R1, lower values in the lateral temporal and parietal ROIs were associated with worse executive functioning, language and attention, and lower occipital R1 with lower language and attention scores. When [18F]flortaucipir BPND and R1 were modelled simultaneously, associations between lower R1 in the lateral temporal ROI and worse attention remained, as well as for lower parietal R1 and worse executive functioning and attention. Conclusion: Tau pathology was associated with locally reduced rCBF. Tau pathology and low rCBF were both independently associated with worse cognitive performance. For tau pathology, these associations spanned widespread neocortex, while for rCBF, independent associations were restricted to lateral temporal and parietal regions and the executive functioning and attention domains. These findings indicate that each biomarker may independently contribute to cognitive impairment in AD.

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Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, Cognition, Relative cerebral blood flow, Tau, [F]flortaucipir PET
in
European Journal of Nuclear Medicine and Molecular Imaging
volume
47
issue
13
pages
11 pages
publisher
Springer
external identifiers
  • scopus:85085514459
  • pmid:32462397
ISSN
1619-7070
DOI
10.1007/s00259-020-04831-w
language
English
LU publication?
yes
id
8351465a-068a-4757-843a-072381739126
date added to LUP
2020-06-16 12:37:45
date last changed
2021-01-26 03:44:58
@article{8351465a-068a-4757-843a-072381739126,
  abstract     = {<p>Purpose: We aimed to investigate associations between tau pathology and relative cerebral blood flow (rCBF), and their relationship with cognition in Alzheimer’s disease (AD), by using a single dynamic [<sup>18</sup>F]flortaucipir positron emission tomography (PET) scan. Methods: Seventy-one subjects with AD (66 ± 8 years, mini-mental state examination (MMSE) 23 ± 4) underwent a dynamic 130-min [<sup>18</sup>F]flortaucipir PET scan. Cognitive assessment consisted of composite scores of four cognitive domains. For tau pathology and rCBF, receptor parametric mapping (cerebellar gray matter reference region) was used to create uncorrected and partial volume-corrected parametric images of non-displaceable binding potential (BP<sub>ND</sub>) and R<sub>1</sub>, respectively. (Voxel-wise) linear regressions were used to investigate associations between BP<sub>ND</sub> and/or R<sub>1</sub> and cognition<sub>.</sub> Results: Higher [<sup>18</sup>F]flortaucipir BP<sub>ND</sub> was associated with lower R<sub>1</sub> in the lateral temporal, parietal and occipital regions. Higher medial temporal BP<sub>ND</sub> was associated with worse memory, and higher lateral temporal BP<sub>ND</sub> with worse executive functioning and language. Higher parietal BP<sub>ND</sub> was associated with worse executive functioning, language and attention, and higher occipital BP<sub>ND</sub> with lower cognitive scores across all domains. Higher frontal BP<sub>ND</sub> was associated with worse executive function and attention. For [<sup>18</sup>F]flortaucipir R<sub>1</sub>, lower values in the lateral temporal and parietal ROIs were associated with worse executive functioning, language and attention, and lower occipital R<sub>1</sub> with lower language and attention scores. When [<sup>18</sup>F]flortaucipir BP<sub>ND</sub> and R<sub>1</sub> were modelled simultaneously, associations between lower R<sub>1</sub> in the lateral temporal ROI and worse attention remained, as well as for lower parietal R<sub>1</sub> and worse executive functioning and attention. Conclusion: Tau pathology was associated with locally reduced rCBF. Tau pathology and low rCBF were both independently associated with worse cognitive performance. For tau pathology, these associations spanned widespread neocortex, while for rCBF, independent associations were restricted to lateral temporal and parietal regions and the executive functioning and attention domains. These findings indicate that each biomarker may independently contribute to cognitive impairment in AD.</p>},
  author       = {Visser, Denise and Wolters, Emma E. and Verfaillie, Sander C.J. and Coomans, Emma M. and Timmers, Tessa and Tuncel, Hayel and Reimand, Juhan and Boellaard, Ronald and Windhorst, Albert D. and Scheltens, Philip and van der Flier, Wiesje M. and Ossenkoppele, Rik and van Berckel, Bart N.M.},
  issn         = {1619-7070},
  language     = {eng},
  number       = {13},
  pages        = {3165--3175},
  publisher    = {Springer},
  series       = {European Journal of Nuclear Medicine and Molecular Imaging},
  title        = {Tau pathology and relative cerebral blood flow are independently associated with cognition in Alzheimer’s disease},
  url          = {http://dx.doi.org/10.1007/s00259-020-04831-w},
  doi          = {10.1007/s00259-020-04831-w},
  volume       = {47},
  year         = {2020},
}