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Tau pathology as determinant of changes in atrophy and cerebral blood flow : a multi-modal longitudinal imaging study

Visser, Denise ; Verfaillie, Sander C.J. ; Bosch, Iris ; Brouwer, Iman ; Tuncel, Hayel ; Coomans, Emma M. LU ; Rikken, Roos M. ; Mastenbroek, Sophie E. LU ; Golla, Sandeep S.V. and Barkhof, Frederik , et al. (2023) In European Journal of Nuclear Medicine and Molecular Imaging 50(8). p.2409-2419
Abstract

Purpose: Tau pathology is associated with concurrent atrophy and decreased cerebral blood flow (CBF) in Alzheimer’s disease (AD), but less is known about their temporal relationships. Our aim was therefore to investigate the association of concurrent and longitudinal tau PET with longitudinal changes in atrophy and relative CBF. Methods: We included 61 individuals from the Amsterdam Dementia Cohort (mean age 65.1 ± 7.5 years, 44% female, 57% amyloid-β positive [Aβ +], 26 cognitively impaired [CI]) who underwent dynamic [18F]flortaucipir PET and structural MRI at baseline and 25 ± 5 months follow-up. In addition, we included 86 individuals (68 CI) who only underwent baseline dynamic [18F]flortaucipir PET and MRI... (More)

Purpose: Tau pathology is associated with concurrent atrophy and decreased cerebral blood flow (CBF) in Alzheimer’s disease (AD), but less is known about their temporal relationships. Our aim was therefore to investigate the association of concurrent and longitudinal tau PET with longitudinal changes in atrophy and relative CBF. Methods: We included 61 individuals from the Amsterdam Dementia Cohort (mean age 65.1 ± 7.5 years, 44% female, 57% amyloid-β positive [Aβ +], 26 cognitively impaired [CI]) who underwent dynamic [18F]flortaucipir PET and structural MRI at baseline and 25 ± 5 months follow-up. In addition, we included 86 individuals (68 CI) who only underwent baseline dynamic [18F]flortaucipir PET and MRI scans to increase power in our statistical models. We obtained [18F]flortaucipir PET binding potential (BPND) and R1 values reflecting tau load and relative CBF, respectively, and computed cortical thickness from the structural MRI scans using FreeSurfer. We assessed the regional associations between i) baseline and ii) annual change in tau PET BPND in Braak I, III/IV, and V/VI regions and cortical thickness or R1 in cortical gray matter regions (spanning the whole brain) over time using linear mixed models with random intercepts adjusted for age, sex, time between baseline and follow-up assessments, and baseline BPND in case of analyses with annual change as determinant. All analyses were performed in Aβ− cognitively normal (CN) individuals and Aβ+ (CN and CI) individuals separately. Results: In Aβ+ individuals, greater baseline Braak III/IV and V/VI tau PET binding was associated with faster cortical thinning in primarily frontotemporal regions. Annual changes in tau PET were not associated with cortical thinning over time in either Aβ+ or Aβ− individuals. Baseline tau PET was not associated with longitudinal changes in relative CBF, but increases in Braak III/IV tau PET over time were associated with increases in parietal relative CBF over time in Aβ + individuals. Conclusion: We showed that higher tau load was related to accelerated cortical thinning, but not to decreases in relative CBF. Moreover, tau PET load at baseline was a stronger predictor of cortical thinning than change of tau PET signal.

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Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, Atrophy, Cerebral blood flow, Longitudinal, Tau PET
in
European Journal of Nuclear Medicine and Molecular Imaging
volume
50
issue
8
pages
2409 - 2419
publisher
Springer
external identifiers
  • scopus:85151135755
  • pmid:36976303
ISSN
1619-7070
DOI
10.1007/s00259-023-06196-2
language
English
LU publication?
yes
id
a2b91912-2132-4370-a293-cde50e159526
date added to LUP
2023-05-24 13:49:59
date last changed
2024-02-19 20:12:45
@article{a2b91912-2132-4370-a293-cde50e159526,
  abstract     = {{<p>Purpose: Tau pathology is associated with concurrent atrophy and decreased cerebral blood flow (CBF) in Alzheimer’s disease (AD), but less is known about their temporal relationships. Our aim was therefore to investigate the association of concurrent and longitudinal tau PET with longitudinal changes in atrophy and relative CBF. Methods: We included 61 individuals from the Amsterdam Dementia Cohort (mean age 65.1 ± 7.5 years, 44% female, 57% amyloid-β positive [Aβ +], 26 cognitively impaired [CI]) who underwent dynamic [<sup>18</sup>F]flortaucipir PET and structural MRI at baseline and 25 ± 5 months follow-up. In addition, we included 86 individuals (68 CI) who only underwent baseline dynamic [<sup>18</sup>F]flortaucipir PET and MRI scans to increase power in our statistical models. We obtained [<sup>18</sup>F]flortaucipir PET binding potential (BP<sub>ND</sub>) and R<sub>1</sub> values reflecting tau load and relative CBF, respectively, and computed cortical thickness from the structural MRI scans using FreeSurfer. We assessed the regional associations between i) baseline and ii) annual change in tau PET BP<sub>ND</sub> in Braak I, III/IV, and V/VI regions and cortical thickness or R<sub>1</sub> in cortical gray matter regions (spanning the whole brain) over time using linear mixed models with random intercepts adjusted for age, sex, time between baseline and follow-up assessments, and baseline BP<sub>ND</sub> in case of analyses with annual change as determinant. All analyses were performed in Aβ− cognitively normal (CN) individuals and Aβ+ (CN and CI) individuals separately. Results: In Aβ+ individuals, greater baseline Braak III/IV and V/VI tau PET binding was associated with faster cortical thinning in primarily frontotemporal regions. Annual changes in tau PET were not associated with cortical thinning over time in either Aβ+ or Aβ− individuals. Baseline tau PET was not associated with longitudinal changes in relative CBF, but increases in Braak III/IV tau PET over time were associated with increases in parietal relative CBF over time in Aβ + individuals. Conclusion: We showed that higher tau load was related to accelerated cortical thinning, but not to decreases in relative CBF. Moreover, tau PET load at baseline was a stronger predictor of cortical thinning than change of tau PET signal.</p>}},
  author       = {{Visser, Denise and Verfaillie, Sander C.J. and Bosch, Iris and Brouwer, Iman and Tuncel, Hayel and Coomans, Emma M. and Rikken, Roos M. and Mastenbroek, Sophie E. and Golla, Sandeep S.V. and Barkhof, Frederik and van de Giessen, Elsmarieke and van Berckel, Bart N.M. and van der Flier, Wiesje M. and Ossenkoppele, Rik}},
  issn         = {{1619-7070}},
  keywords     = {{Alzheimer’s disease; Atrophy; Cerebral blood flow; Longitudinal; Tau PET}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{2409--2419}},
  publisher    = {{Springer}},
  series       = {{European Journal of Nuclear Medicine and Molecular Imaging}},
  title        = {{Tau pathology as determinant of changes in atrophy and cerebral blood flow : a multi-modal longitudinal imaging study}},
  url          = {{http://dx.doi.org/10.1007/s00259-023-06196-2}},
  doi          = {{10.1007/s00259-023-06196-2}},
  volume       = {{50}},
  year         = {{2023}},
}