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The effect of amyloid deposition on longitudinal resting-state functional connectivity in cognitively normal older adults

BACKGROUND: Pathological processes contributing to Alzheimer’s disease begin decades prior to the onset of clinical symptoms. There is significant variation in cognitive changes in the presence of pathology, functional connectivity may be a marker of compensation to amyloid; however, this is not wel...

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Autores principales: Lin, Chemin, Ly, Maria, Karim, Helmet T., Wei, Wenjing, Snitz, Beth E., Klunk, William E., Aizenstein, Howard J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945413/
https://www.ncbi.nlm.nih.gov/pubmed/31907079
http://dx.doi.org/10.1186/s13195-019-0573-1
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author Lin, Chemin
Ly, Maria
Karim, Helmet T.
Wei, Wenjing
Snitz, Beth E.
Klunk, William E.
Aizenstein, Howard J.
author_facet Lin, Chemin
Ly, Maria
Karim, Helmet T.
Wei, Wenjing
Snitz, Beth E.
Klunk, William E.
Aizenstein, Howard J.
author_sort Lin, Chemin
collection PubMed
description BACKGROUND: Pathological processes contributing to Alzheimer’s disease begin decades prior to the onset of clinical symptoms. There is significant variation in cognitive changes in the presence of pathology, functional connectivity may be a marker of compensation to amyloid; however, this is not well understood. METHODS: We recruited 64 cognitively normal older adults who underwent neuropsychological testing and biannual magnetic resonance imaging (MRI), amyloid imaging with Pittsburgh compound B (PiB)-PET, and glucose metabolism (FDG)-PET imaging for up to 6 years. Resting-state MRI was used to estimate connectivity of seven canonical neural networks using template-based rotation. Using voxel-wise paired t-tests, we identified neural networks that displayed significant changes in connectivity across time. We investigated associations among amyloid and longitudinal changes in connectivity and cognitive function by domains. RESULTS: Left middle frontal gyrus connectivity within the memory encoding network increased over time, but the rate of change was lower with greater amyloid. This was no longer significant in an analysis where we limited the sample to only those with two time points. We found limited decline in cognitive domains overall. Greater functional connectivity was associated with better attention/processing speed and executive function (independent of time) in those with lower amyloid but was associated with worse function with greater amyloid. CONCLUSIONS: Increased functional connectivity serves to preserve cognitive function in normal aging and may fail in the presence of pathology consistent with compensatory models. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13195-019-0573-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-69454132020-01-09 The effect of amyloid deposition on longitudinal resting-state functional connectivity in cognitively normal older adults Lin, Chemin Ly, Maria Karim, Helmet T. Wei, Wenjing Snitz, Beth E. Klunk, William E. Aizenstein, Howard J. Alzheimers Res Ther Research BACKGROUND: Pathological processes contributing to Alzheimer’s disease begin decades prior to the onset of clinical symptoms. There is significant variation in cognitive changes in the presence of pathology, functional connectivity may be a marker of compensation to amyloid; however, this is not well understood. METHODS: We recruited 64 cognitively normal older adults who underwent neuropsychological testing and biannual magnetic resonance imaging (MRI), amyloid imaging with Pittsburgh compound B (PiB)-PET, and glucose metabolism (FDG)-PET imaging for up to 6 years. Resting-state MRI was used to estimate connectivity of seven canonical neural networks using template-based rotation. Using voxel-wise paired t-tests, we identified neural networks that displayed significant changes in connectivity across time. We investigated associations among amyloid and longitudinal changes in connectivity and cognitive function by domains. RESULTS: Left middle frontal gyrus connectivity within the memory encoding network increased over time, but the rate of change was lower with greater amyloid. This was no longer significant in an analysis where we limited the sample to only those with two time points. We found limited decline in cognitive domains overall. Greater functional connectivity was associated with better attention/processing speed and executive function (independent of time) in those with lower amyloid but was associated with worse function with greater amyloid. CONCLUSIONS: Increased functional connectivity serves to preserve cognitive function in normal aging and may fail in the presence of pathology consistent with compensatory models. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13195-019-0573-1) contains supplementary material, which is available to authorized users. BioMed Central 2020-01-06 /pmc/articles/PMC6945413/ /pubmed/31907079 http://dx.doi.org/10.1186/s13195-019-0573-1 Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Lin, Chemin
Ly, Maria
Karim, Helmet T.
Wei, Wenjing
Snitz, Beth E.
Klunk, William E.
Aizenstein, Howard J.
The effect of amyloid deposition on longitudinal resting-state functional connectivity in cognitively normal older adults
title The effect of amyloid deposition on longitudinal resting-state functional connectivity in cognitively normal older adults
title_full The effect of amyloid deposition on longitudinal resting-state functional connectivity in cognitively normal older adults
title_fullStr The effect of amyloid deposition on longitudinal resting-state functional connectivity in cognitively normal older adults
title_full_unstemmed The effect of amyloid deposition on longitudinal resting-state functional connectivity in cognitively normal older adults
title_short The effect of amyloid deposition on longitudinal resting-state functional connectivity in cognitively normal older adults
title_sort effect of amyloid deposition on longitudinal resting-state functional connectivity in cognitively normal older adults
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945413/
https://www.ncbi.nlm.nih.gov/pubmed/31907079
http://dx.doi.org/10.1186/s13195-019-0573-1
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