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Spatial patterns of tau deposition are associated with amyloid, ApoE, sex, and cognitive decline in older adults

Pereira, Joana B. LU ; Harrison, Theresa M. ; La Joie, Renaud ; Baker, Suzanne L. and Jagust, William J. (2020) In European Journal of Nuclear Medicine and Molecular Imaging
Abstract

Purpose: The abnormal deposition of tau begins before the onset of clinical symptoms and seems to target specific brain networks. The aim of this study is to identify the spatial patterns of tau deposition in cognitively normal older adults and assess whether they are related to amyloid-β (Aβ), APOE, sex, and longitudinal cognitive decline. Methods: We included 114 older adults with cross-sectional flortaucipir (FTP) and Pittsburgh Compound-B PET in addition to longitudinal cognitive testing. A voxel-wise independent component analysis was applied to FTP images to identify the spatial patterns of tau deposition. We then assessed whether tau within these patterns differed by Aβ status, APOE genotype, and sex. Linear mixed effects models... (More)

Purpose: The abnormal deposition of tau begins before the onset of clinical symptoms and seems to target specific brain networks. The aim of this study is to identify the spatial patterns of tau deposition in cognitively normal older adults and assess whether they are related to amyloid-β (Aβ), APOE, sex, and longitudinal cognitive decline. Methods: We included 114 older adults with cross-sectional flortaucipir (FTP) and Pittsburgh Compound-B PET in addition to longitudinal cognitive testing. A voxel-wise independent component analysis was applied to FTP images to identify the spatial patterns of tau deposition. We then assessed whether tau within these patterns differed by Aβ status, APOE genotype, and sex. Linear mixed effects models were built to test whether tau in each component predicted cognitive decline. Finally, we ordered the spatial components based on the frequency of high tau deposition to model tau spread. Results: We found 10 biologically plausible tau patterns in the whole sample. There was greater tau in medial temporal, occipital, and orbitofrontal components in Aβ-positive compared with Aβ-negative individuals; in the parahippocampal component in ε3ε3 compared with ε2ε3 carriers; and in temporo-parietal and anterior frontal components in women compared with men. Higher tau in temporal and frontal components predicted longitudinal cognitive decline in memory and executive functions, respectively. Tau deposition was most frequently observed in medial temporal and ventral cortical areas, followed by lateral and primary areas. Conclusions: These findings suggest that the spatial patterns of tau in asymptomatic individuals are clinically meaningful and are associated with Aβ, APOE ε2ε3, sex and cognitive decline. These patterns could be used to predict the regional spread of tau and perform in vivo tau staging in older adults.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amyloid, APOE, Cognitive decline, Flortaucipir PET, Older adults, Sex
in
European Journal of Nuclear Medicine and Molecular Imaging
publisher
Springer
external identifiers
  • scopus:85077525153
  • pmid:31915896
ISSN
1619-7070
DOI
10.1007/s00259-019-04669-x
language
English
LU publication?
yes
id
fe9591e3-7e8c-49e5-85ba-c12f0e0ed8ce
date added to LUP
2020-01-30 15:35:23
date last changed
2024-07-11 11:44:20
@article{fe9591e3-7e8c-49e5-85ba-c12f0e0ed8ce,
  abstract     = {{<p>Purpose: The abnormal deposition of tau begins before the onset of clinical symptoms and seems to target specific brain networks. The aim of this study is to identify the spatial patterns of tau deposition in cognitively normal older adults and assess whether they are related to amyloid-β (Aβ), APOE, sex, and longitudinal cognitive decline. Methods: We included 114 older adults with cross-sectional flortaucipir (FTP) and Pittsburgh Compound-B PET in addition to longitudinal cognitive testing. A voxel-wise independent component analysis was applied to FTP images to identify the spatial patterns of tau deposition. We then assessed whether tau within these patterns differed by Aβ status, APOE genotype, and sex. Linear mixed effects models were built to test whether tau in each component predicted cognitive decline. Finally, we ordered the spatial components based on the frequency of high tau deposition to model tau spread. Results: We found 10 biologically plausible tau patterns in the whole sample. There was greater tau in medial temporal, occipital, and orbitofrontal components in Aβ-positive compared with Aβ-negative individuals; in the parahippocampal component in ε3ε3 compared with ε2ε3 carriers; and in temporo-parietal and anterior frontal components in women compared with men. Higher tau in temporal and frontal components predicted longitudinal cognitive decline in memory and executive functions, respectively. Tau deposition was most frequently observed in medial temporal and ventral cortical areas, followed by lateral and primary areas. Conclusions: These findings suggest that the spatial patterns of tau in asymptomatic individuals are clinically meaningful and are associated with Aβ, APOE ε2ε3, sex and cognitive decline. These patterns could be used to predict the regional spread of tau and perform in vivo tau staging in older adults.</p>}},
  author       = {{Pereira, Joana B. and Harrison, Theresa M. and La Joie, Renaud and Baker, Suzanne L. and Jagust, William J.}},
  issn         = {{1619-7070}},
  keywords     = {{Amyloid; APOE; Cognitive decline; Flortaucipir PET; Older adults; Sex}},
  language     = {{eng}},
  month        = {{01}},
  publisher    = {{Springer}},
  series       = {{European Journal of Nuclear Medicine and Molecular Imaging}},
  title        = {{Spatial patterns of tau deposition are associated with amyloid, ApoE, sex, and cognitive decline in older adults}},
  url          = {{http://dx.doi.org/10.1007/s00259-019-04669-x}},
  doi          = {{10.1007/s00259-019-04669-x}},
  year         = {{2020}},
}