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Investigating Associations Between Inflammatory Biomarkers, Gray Matter, Neurofilament Light and Cognitive Performance in Healthy Older Adults
Background: Exploring biological variables that may serve as indicators of the development and progression of cognitive decline is currently a high-priority research area. Recent studies have demonstrated that during normal aging, individuals experience increased inflammation throughout the brain an...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446648/ https://www.ncbi.nlm.nih.gov/pubmed/34539381 http://dx.doi.org/10.3389/fnagi.2021.719553 |
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author | Karoly, Hollis C. Skrzynski, Carillon J. Moe, Erin Bryan, Angela D. Hutchison, Kent E. |
author_facet | Karoly, Hollis C. Skrzynski, Carillon J. Moe, Erin Bryan, Angela D. Hutchison, Kent E. |
author_sort | Karoly, Hollis C. |
collection | PubMed |
description | Background: Exploring biological variables that may serve as indicators of the development and progression of cognitive decline is currently a high-priority research area. Recent studies have demonstrated that during normal aging, individuals experience increased inflammation throughout the brain and body, which may be linked to cognitive impairment and reduced gray matter volume in the brain. Neurofilament light polypeptide (NfL), which is released into the circulation following neuronal damage, has been proposed as a biomarker for neurodegenerative diseases, and may also have utility in the context of normal aging. The present study tested associations between age, peripheral levels of the pro-inflammatory cytokine IL-6, peripheral NfL, brain volume, and cognitive performance in a sample of healthy adults over 60 years old. Methods: Of the 273 individuals who participated in this study, 173 had useable neuroimaging data, a subset of whom had useable blood data (used for quantifying IL-6 and NfL) and completed a cognitive task. Gray matter (GM) thickness values were extracted from brain areas of interest using Freesurfer. Regression models were used to test relationships between IL-6, NfL, GM, and cognitive performance. To test putative functional relationships between these variables, exploratory path analytic models were estimated, in which the relationship between age, IL-6, and working memory performance were linked via four different operationalizations of brain health: (1) a latent GM variable composed of several regions linked to cognitive impairment, (2) NfL alone, (3) NfL combined with the GM latent variable, and (4) the hippocampus alone. Results: Regression models showed that IL-6 and NfL were significantly negatively associated with GM volume and that GM was positively associated with cognitive performance. The path analytic models indicated that age and cognitive performance are linked by GM in the hippocampus as well as several other regions previously associated with cognitive impairment, but not by NfL alone. Peripheral IL-6 was not associated with age in any of the path models. Conclusions: Results suggest that among healthy older adults, there are several GM regions that link age and cognitive performance. Notably, NfL alone is not a sufficient marker of brain changes associated with aging, inflammation, and cognitive performance. |
format | Online Article Text |
id | pubmed-8446648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84466482021-09-18 Investigating Associations Between Inflammatory Biomarkers, Gray Matter, Neurofilament Light and Cognitive Performance in Healthy Older Adults Karoly, Hollis C. Skrzynski, Carillon J. Moe, Erin Bryan, Angela D. Hutchison, Kent E. Front Aging Neurosci Neuroscience Background: Exploring biological variables that may serve as indicators of the development and progression of cognitive decline is currently a high-priority research area. Recent studies have demonstrated that during normal aging, individuals experience increased inflammation throughout the brain and body, which may be linked to cognitive impairment and reduced gray matter volume in the brain. Neurofilament light polypeptide (NfL), which is released into the circulation following neuronal damage, has been proposed as a biomarker for neurodegenerative diseases, and may also have utility in the context of normal aging. The present study tested associations between age, peripheral levels of the pro-inflammatory cytokine IL-6, peripheral NfL, brain volume, and cognitive performance in a sample of healthy adults over 60 years old. Methods: Of the 273 individuals who participated in this study, 173 had useable neuroimaging data, a subset of whom had useable blood data (used for quantifying IL-6 and NfL) and completed a cognitive task. Gray matter (GM) thickness values were extracted from brain areas of interest using Freesurfer. Regression models were used to test relationships between IL-6, NfL, GM, and cognitive performance. To test putative functional relationships between these variables, exploratory path analytic models were estimated, in which the relationship between age, IL-6, and working memory performance were linked via four different operationalizations of brain health: (1) a latent GM variable composed of several regions linked to cognitive impairment, (2) NfL alone, (3) NfL combined with the GM latent variable, and (4) the hippocampus alone. Results: Regression models showed that IL-6 and NfL were significantly negatively associated with GM volume and that GM was positively associated with cognitive performance. The path analytic models indicated that age and cognitive performance are linked by GM in the hippocampus as well as several other regions previously associated with cognitive impairment, but not by NfL alone. Peripheral IL-6 was not associated with age in any of the path models. Conclusions: Results suggest that among healthy older adults, there are several GM regions that link age and cognitive performance. Notably, NfL alone is not a sufficient marker of brain changes associated with aging, inflammation, and cognitive performance. Frontiers Media S.A. 2021-09-03 /pmc/articles/PMC8446648/ /pubmed/34539381 http://dx.doi.org/10.3389/fnagi.2021.719553 Text en Copyright © 2021 Karoly, Skrzynski, Moe, Bryan and Hutchison. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Karoly, Hollis C. Skrzynski, Carillon J. Moe, Erin Bryan, Angela D. Hutchison, Kent E. Investigating Associations Between Inflammatory Biomarkers, Gray Matter, Neurofilament Light and Cognitive Performance in Healthy Older Adults |
title | Investigating Associations Between Inflammatory Biomarkers, Gray Matter, Neurofilament Light and Cognitive Performance in Healthy Older Adults |
title_full | Investigating Associations Between Inflammatory Biomarkers, Gray Matter, Neurofilament Light and Cognitive Performance in Healthy Older Adults |
title_fullStr | Investigating Associations Between Inflammatory Biomarkers, Gray Matter, Neurofilament Light and Cognitive Performance in Healthy Older Adults |
title_full_unstemmed | Investigating Associations Between Inflammatory Biomarkers, Gray Matter, Neurofilament Light and Cognitive Performance in Healthy Older Adults |
title_short | Investigating Associations Between Inflammatory Biomarkers, Gray Matter, Neurofilament Light and Cognitive Performance in Healthy Older Adults |
title_sort | investigating associations between inflammatory biomarkers, gray matter, neurofilament light and cognitive performance in healthy older adults |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446648/ https://www.ncbi.nlm.nih.gov/pubmed/34539381 http://dx.doi.org/10.3389/fnagi.2021.719553 |
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