Association of peripheral inflammatory markers with connectivity in large-scale functional brain networks of non-demented older adults.
Alzheimer’s disease
Default mode network
Dorsal attention network
Functional connectivity
Inflammation
Interleukin 6
Resting-state functional magnetic resonance imaging
Tumor necrosis factor
Journal
Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
03
09
2019
revised:
13
12
2019
accepted:
06
01
2020
pubmed:
15
1
2020
medline:
28
4
2021
entrez:
15
1
2020
Statut:
ppublish
Résumé
Systemic inflammation has emerged as a risk factor for cognitive decline and Alzheimer's disease, but inflammation's effect on distributed brain networks is unclear. We examined the relationship between peripheral inflammatory markers and subsequent functional connectivity within five large-scale cognitive networks and evaluated the modifying role of cortical amyloid and APOE ε4 status. Blood levels of soluble tumor necrosis factor-alpha receptor-1 and interleukin 6 were assessed in 176 participants (at baseline mean age: 65 (SD 9) years; 63% women; 85% cognitively normal, 15% mild cognitive impairment (MCI)) and were combined to derive an Inflammatory Index. Approximately six years later, participants underwent resting-state functional magnetic resonance imaging to quantify functional connectivity; a subset of 137 participants also underwent Using linear regression models adjusted for demographic characteristics and cardiovascular risk factors, a higher Inflammatory Index was associated with lower connectivity within the Default Mode (β = -0.013; 95% CI: -0.023, -0.003) and the Dorsal Attention Networks (β = -0.017; 95% CI: -0.028, -0.006). The strength of these associations did not vary by amyloid status (positive/negative). However, there was a significant interaction between Inflammatory Index and APOE ε4 status, whereby ε4-positive participants with a higher Inflammatory Index demonstrated lower connectivity. Inflammatory Index was unrelated to connectivity within other large-scale cognitive networks (Control, Limbic, and Salience/Ventral Attention networks). Peripheral pro-inflammatory signaling in older adults without dementia, especially among APOE ε4-positive individuals, is associated with altered connectivity within two large-scale cognitive networks.
Sections du résumé
BACKGROUND
Systemic inflammation has emerged as a risk factor for cognitive decline and Alzheimer's disease, but inflammation's effect on distributed brain networks is unclear. We examined the relationship between peripheral inflammatory markers and subsequent functional connectivity within five large-scale cognitive networks and evaluated the modifying role of cortical amyloid and APOE ε4 status.
METHODS
Blood levels of soluble tumor necrosis factor-alpha receptor-1 and interleukin 6 were assessed in 176 participants (at baseline mean age: 65 (SD 9) years; 63% women; 85% cognitively normal, 15% mild cognitive impairment (MCI)) and were combined to derive an Inflammatory Index. Approximately six years later, participants underwent resting-state functional magnetic resonance imaging to quantify functional connectivity; a subset of 137 participants also underwent
RESULTS
Using linear regression models adjusted for demographic characteristics and cardiovascular risk factors, a higher Inflammatory Index was associated with lower connectivity within the Default Mode (β = -0.013; 95% CI: -0.023, -0.003) and the Dorsal Attention Networks (β = -0.017; 95% CI: -0.028, -0.006). The strength of these associations did not vary by amyloid status (positive/negative). However, there was a significant interaction between Inflammatory Index and APOE ε4 status, whereby ε4-positive participants with a higher Inflammatory Index demonstrated lower connectivity. Inflammatory Index was unrelated to connectivity within other large-scale cognitive networks (Control, Limbic, and Salience/Ventral Attention networks).
CONCLUSION
Peripheral pro-inflammatory signaling in older adults without dementia, especially among APOE ε4-positive individuals, is associated with altered connectivity within two large-scale cognitive networks.
Identifiants
pubmed: 31935468
pii: S0889-1591(19)31061-X
doi: 10.1016/j.bbi.2020.01.006
pmc: PMC7316598
mid: NIHMS1552811
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
388-396Subventions
Organisme : NIA NIH HHS
ID : T32 AG027668
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005146
Pays : United States
Organisme : NIA NIH HHS
ID : K01 AG050699
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB015909
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066507
Pays : United States
Organisme : NIA NIH HHS
ID : K23 AG064122
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG021334
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG033655
Pays : United States
Organisme : NIH HHS
ID : S10 OD021648
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG050560
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.