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Association Between Earliest Amyloid Uptake and Functional Connectivity in Cognitively Unimpaired Elderly

Hahn, Andreas; Strandberg, Tor O LU ; Stomrud, Erik LU ; Nilsson, Markus LU ; van Westen, Danielle LU ; Palmqvist, Sebastian LU ; Ossenkoppele, Rik LU and Hansson, Oskar LU (2019) In Cerebral Cortex 29. p.2173-2182
Abstract

Alterations in cognitive performance have been noted in nondemented subjects with elevated accumulation of amyloid-β (Aβ) fibrils. However, it is not yet understood whether brain function is already influenced by Aβ deposition during the very earliest stages of the disease. We therefore investigated associations between [18F]Flutemetamol PET, resting-state functional connectivity, gray and white matter structure and cognitive performance in 133 cognitively normal elderly that exhibited normal global Aβ PET levels. [18F]Flutemetamol uptake in regions known to accumulate Aβ fibrils early in preclinical AD (i.e., mainly certain parts of the default-mode network) was positively associated with dynamic but not static functional connectivity... (More)

Alterations in cognitive performance have been noted in nondemented subjects with elevated accumulation of amyloid-β (Aβ) fibrils. However, it is not yet understood whether brain function is already influenced by Aβ deposition during the very earliest stages of the disease. We therefore investigated associations between [18F]Flutemetamol PET, resting-state functional connectivity, gray and white matter structure and cognitive performance in 133 cognitively normal elderly that exhibited normal global Aβ PET levels. [18F]Flutemetamol uptake in regions known to accumulate Aβ fibrils early in preclinical AD (i.e., mainly certain parts of the default-mode network) was positively associated with dynamic but not static functional connectivity (r = 0.77). Dynamic functional connectivity was further related to better cognitive performance (r = 0.21-0.72). No significant associations were found for Aβ uptake with gray matter volume or white matter diffusivity. The findings demonstrate that the earliest accumulation of Aβ fibrils is associated with increased functional connectivity, which occurs before any structural alterations. The enhanced functional connectivity may reflect a compensatory mechanism to maintain high cognitive performance in the presence of increasing amyloid accumulation during the earliest phases of AD.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cerebral Cortex
volume
29
pages
2173 - 2182
publisher
Oxford University Press
external identifiers
  • scopus:85063410612
ISSN
1460-2199
DOI
10.1093/cercor/bhz020
language
English
LU publication?
yes
id
5271539c-9004-4de3-8551-7ec613882b55
date added to LUP
2019-05-27 15:24:52
date last changed
2019-09-17 04:55:11
@article{5271539c-9004-4de3-8551-7ec613882b55,
  abstract     = {<p>Alterations in cognitive performance have been noted in nondemented subjects with elevated accumulation of amyloid-β (Aβ) fibrils. However, it is not yet understood whether brain function is already influenced by Aβ deposition during the very earliest stages of the disease. We therefore investigated associations between [18F]Flutemetamol PET, resting-state functional connectivity, gray and white matter structure and cognitive performance in 133 cognitively normal elderly that exhibited normal global Aβ PET levels. [18F]Flutemetamol uptake in regions known to accumulate Aβ fibrils early in preclinical AD (i.e., mainly certain parts of the default-mode network) was positively associated with dynamic but not static functional connectivity (r = 0.77). Dynamic functional connectivity was further related to better cognitive performance (r = 0.21-0.72). No significant associations were found for Aβ uptake with gray matter volume or white matter diffusivity. The findings demonstrate that the earliest accumulation of Aβ fibrils is associated with increased functional connectivity, which occurs before any structural alterations. The enhanced functional connectivity may reflect a compensatory mechanism to maintain high cognitive performance in the presence of increasing amyloid accumulation during the earliest phases of AD.</p>},
  author       = {Hahn, Andreas and Strandberg, Tor O and Stomrud, Erik and Nilsson, Markus and van Westen, Danielle and Palmqvist, Sebastian and Ossenkoppele, Rik and Hansson, Oskar},
  issn         = {1460-2199},
  language     = {eng},
  pages        = {2173--2182},
  publisher    = {Oxford University Press},
  series       = {Cerebral Cortex},
  title        = {Association Between Earliest Amyloid Uptake and Functional Connectivity in Cognitively Unimpaired Elderly},
  url          = {http://dx.doi.org/10.1093/cercor/bhz020},
  volume       = {29},
  year         = {2019},
}