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Associations between quantitative [18F]flortaucipir tau PET and atrophy across the Alzheimer's disease spectrum

Timmers, Tessa; Ossenkoppele, Rik LU ; Wolters, Emma E.; Verfaillie, Sander C.J.; Visser, Denise; Golla, Sandeep S.V.; Barkhof, Frederik; Scheltens, Philip; Boellaard, Ronald and Van Der Flier, Wiesje M., et al. (2019) In Alzheimer's Research and Therapy 11(1).
Abstract

Background: Neuropathological studies have linked tau aggregates to neuronal loss. To describe the spatial distribution of neurofibrillary tangle pathology in post-mortem tissue, Braak staging has been used. The aim of this study was to examine in vivo associations between tau pathology, quantified with [18F]flortaucipir PET in regions corresponding to Braak stages, and atrophy across the Alzheimer's disease (AD) spectrum. Methods: We included 100 subjects, including 58 amyloid-β positive patients with mild cognitive impairment (MCI, n = 6) or AD dementia (n = 52) and 42 controls with subjective cognitive decline (36% amyloid-β positive). All subjects underwent a dynamic [18F]flortaucipir PET to generate... (More)

Background: Neuropathological studies have linked tau aggregates to neuronal loss. To describe the spatial distribution of neurofibrillary tangle pathology in post-mortem tissue, Braak staging has been used. The aim of this study was to examine in vivo associations between tau pathology, quantified with [18F]flortaucipir PET in regions corresponding to Braak stages, and atrophy across the Alzheimer's disease (AD) spectrum. Methods: We included 100 subjects, including 58 amyloid-β positive patients with mild cognitive impairment (MCI, n = 6) or AD dementia (n = 52) and 42 controls with subjective cognitive decline (36% amyloid-β positive). All subjects underwent a dynamic [18F]flortaucipir PET to generate non-displaceable binding potential (BPND) maps. We extracted average [18F]flortaucipir BPND entorhinal, Braak III-IV (limbic) and Braak V-VI (neocortical) regions of interest (ROIs). T1-weighted MRI was used to assess gray matter (GM) volumes. We performed linear regression analyses using [18F]flortaucipir BPND ROIs as independent and GM density (ROI or voxelwise) as dependent variable. Results: In MCI/AD subjects (age [mean ± SD] 65 ± 8 years, MMSE 23 ± 4), [18F]flortaucipir BPND was higher than in controls (age 65 ± 8, MMSE 29 ± 1) across all ROIs (entorhinal 0.06 ± 0.21 vs 0.46 ± 0.25 p < 0.001, Braak III-IV 0.11 ± 0.10 vs 0.46 ± 0.26, p < 0.001, Braak V-VI 0.07 ± 0.07 vs 0.38 ± 0.29, p < 0.001). In MCI/AD, greater [18F]flortaucipir BPND in entorhinal cortex was associated with lower GM density in medial temporal lobe (β - 0.40, p < 0.001). Greater [18F]flortaucipir BPND in ROI Braak III-IV and Braak V-VI was associated with smaller GM density in lateral and inferior temporal, parietal, occipital, and frontal lobes (range standardized βs - 0.30 to - 0.55, p < 0.01), but not in medial temporal lobe (β - 0.22, p 0.07). [18F]Flortaucipir BPND in ROI Braak I-II was not associated with GM density loss anywhere. When quantifying [18F]flortaucipir BPND across brain lobes, we observed both local and distant associations with GM atrophy. In controls, there were no significant associations between [18F]flortaucipir BPND and GM density (standardized βs ranging from - 0.24 to 0.02, all p > 0.05). Conclusions: In MCI/AD patients, [18F]flortaucipir binding in entorhinal, limbic, and neocortical regions was associated with cortical atrophy.

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keywords
Alzheimer's disease, Atrophy, MCI (mild cognitive impairment), MRI, PET, Tau
in
Alzheimer's Research and Therapy
volume
11
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85068547893
ISSN
1758-9193
DOI
10.1186/s13195-019-0510-3
language
English
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yes
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6c38dabe-01a6-4df2-9a2d-3efa483e8fba
date added to LUP
2019-07-16 13:06:16
date last changed
2019-08-14 04:41:47
@article{6c38dabe-01a6-4df2-9a2d-3efa483e8fba,
  abstract     = {<p>Background: Neuropathological studies have linked tau aggregates to neuronal loss. To describe the spatial distribution of neurofibrillary tangle pathology in post-mortem tissue, Braak staging has been used. The aim of this study was to examine in vivo associations between tau pathology, quantified with [<sup>18</sup>F]flortaucipir PET in regions corresponding to Braak stages, and atrophy across the Alzheimer's disease (AD) spectrum. Methods: We included 100 subjects, including 58 amyloid-β positive patients with mild cognitive impairment (MCI, n = 6) or AD dementia (n = 52) and 42 controls with subjective cognitive decline (36% amyloid-β positive). All subjects underwent a dynamic [<sup>18</sup>F]flortaucipir PET to generate non-displaceable binding potential (BP<sub>ND</sub>) maps. We extracted average [<sup>18</sup>F]flortaucipir BP<sub>ND</sub> entorhinal, Braak III-IV (limbic) and Braak V-VI (neocortical) regions of interest (ROIs). T1-weighted MRI was used to assess gray matter (GM) volumes. We performed linear regression analyses using [<sup>18</sup>F]flortaucipir BP<sub>ND</sub> ROIs as independent and GM density (ROI or voxelwise) as dependent variable. Results: In MCI/AD subjects (age [mean ± SD] 65 ± 8 years, MMSE 23 ± 4), [<sup>18</sup>F]flortaucipir BP<sub>ND</sub> was higher than in controls (age 65 ± 8, MMSE 29 ± 1) across all ROIs (entorhinal 0.06 ± 0.21 vs 0.46 ± 0.25 p &lt; 0.001, Braak III-IV 0.11 ± 0.10 vs 0.46 ± 0.26, p &lt; 0.001, Braak V-VI 0.07 ± 0.07 vs 0.38 ± 0.29, p &lt; 0.001). In MCI/AD, greater [<sup>18</sup>F]flortaucipir BP<sub>ND</sub> in entorhinal cortex was associated with lower GM density in medial temporal lobe (β - 0.40, p &lt; 0.001). Greater [<sup>18</sup>F]flortaucipir BP<sub>ND</sub> in ROI Braak III-IV and Braak V-VI was associated with smaller GM density in lateral and inferior temporal, parietal, occipital, and frontal lobes (range standardized βs - 0.30 to - 0.55, p &lt; 0.01), but not in medial temporal lobe (β - 0.22, p 0.07). [<sup>18</sup>F]Flortaucipir BP<sub>ND</sub> in ROI Braak I-II was not associated with GM density loss anywhere. When quantifying [<sup>18</sup>F]flortaucipir BP<sub>ND</sub> across brain lobes, we observed both local and distant associations with GM atrophy. In controls, there were no significant associations between [<sup>18</sup>F]flortaucipir BP<sub>ND</sub> and GM density (standardized βs ranging from - 0.24 to 0.02, all p &gt; 0.05). Conclusions: In MCI/AD patients, [<sup>18</sup>F]flortaucipir binding in entorhinal, limbic, and neocortical regions was associated with cortical atrophy.</p>},
  articleno    = {60},
  author       = {Timmers, Tessa and Ossenkoppele, Rik and Wolters, Emma E. and Verfaillie, Sander C.J. and Visser, Denise and Golla, Sandeep S.V. and Barkhof, Frederik and Scheltens, Philip and Boellaard, Ronald and Van Der Flier, Wiesje M. and Van Berckel, Bart N.M.},
  issn         = {1758-9193},
  keyword      = {Alzheimer's disease,Atrophy,MCI (mild cognitive impairment),MRI,PET,Tau},
  language     = {eng},
  month        = {07},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Alzheimer's Research and Therapy},
  title        = {Associations between quantitative [<sup>18</sup>F]flortaucipir tau PET and atrophy across the Alzheimer's disease spectrum},
  url          = {http://dx.doi.org/10.1186/s13195-019-0510-3},
  volume       = {11},
  year         = {2019},
}