Systemic Tumor Necrosis Factor-Alpha Trajectories Relate to Brain Health in Typically Aging Older Adults.
Aged
Aging
/ physiology
Biomarkers
/ blood
Cognition
/ physiology
Executive Function
/ physiology
Female
Follow-Up Studies
Gray Matter
/ diagnostic imaging
Humans
Magnetic Resonance Imaging
Male
Memory, Episodic
Neuropsychological Tests
Tumor Necrosis Factor-alpha
/ blood
White Matter
/ diagnostic imaging
Brain aging
Cognition
Gray matter volume
Inflammation
Neuroimaging
Journal
The journals of gerontology. Series A, Biological sciences and medical sciences
ISSN: 1758-535X
Titre abrégé: J Gerontol A Biol Sci Med Sci
Pays: United States
ID NLM: 9502837
Informations de publication
Date de publication:
13 07 2020
13 07 2020
Historique:
received:
12
03
2019
pubmed:
25
9
2019
medline:
11
2
2021
entrez:
25
9
2019
Statut:
ppublish
Résumé
Central nervous system levels of tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine, regulate the neuroinflammatory response and may play a role in age-related neurodegenerative diseases. The longitudinal relation between peripheral levels of TNF-α and typical brain aging is understudied. We hypothesized that within-person increases in systemic TNF-α would track with poorer brain health outcomes in functionally normal adults. Plasma-based TNF-α concentrations (pg/mL; fasting morning draws) and magnetic resonance imaging were acquired in 424 functionally intact adults (mean age = 71) followed annually for up to 8.4 years (mean follow-up = 2.2 years). Brain outcomes included total gray matter volume and white matter hyperintensities. Cognitive outcomes included composites of memory, executive functioning, and processing speed, as well as Mini-Mental State Examination total scores. Longitudinal mixed-effects models were used, controlling for age, sex, education, and total intracranial volume, as appropriate. TNF-α concentrations significantly increased over time (p < .001). Linear increases in within-person TNF-α were longitudinally associated with declines in gray matter volume (p < .001) and increases in white matter hyperintensities (p = .003). Exploratory analyses suggested that the relation between TNF-α and gray matter volume was curvilinear (TNF-α 2p = .002), such that initial increases in inflammation were associated with more precipitous atrophy. There was a negative linear relationship of within-person changes in TNF-α to Mini-Mental State Examination scores over time (p = .036) but not the cognitive composites (all ps >.05). Systemic inflammation, as indexed by plasma TNF-α, holds potential as a biomarker for age-related declines in brain health.
Sections du résumé
BACKGROUND
Central nervous system levels of tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine, regulate the neuroinflammatory response and may play a role in age-related neurodegenerative diseases. The longitudinal relation between peripheral levels of TNF-α and typical brain aging is understudied. We hypothesized that within-person increases in systemic TNF-α would track with poorer brain health outcomes in functionally normal adults.
METHODS
Plasma-based TNF-α concentrations (pg/mL; fasting morning draws) and magnetic resonance imaging were acquired in 424 functionally intact adults (mean age = 71) followed annually for up to 8.4 years (mean follow-up = 2.2 years). Brain outcomes included total gray matter volume and white matter hyperintensities. Cognitive outcomes included composites of memory, executive functioning, and processing speed, as well as Mini-Mental State Examination total scores. Longitudinal mixed-effects models were used, controlling for age, sex, education, and total intracranial volume, as appropriate.
RESULTS
TNF-α concentrations significantly increased over time (p < .001). Linear increases in within-person TNF-α were longitudinally associated with declines in gray matter volume (p < .001) and increases in white matter hyperintensities (p = .003). Exploratory analyses suggested that the relation between TNF-α and gray matter volume was curvilinear (TNF-α 2p = .002), such that initial increases in inflammation were associated with more precipitous atrophy. There was a negative linear relationship of within-person changes in TNF-α to Mini-Mental State Examination scores over time (p = .036) but not the cognitive composites (all ps >.05).
CONCLUSION
Systemic inflammation, as indexed by plasma TNF-α, holds potential as a biomarker for age-related declines in brain health.
Identifiants
pubmed: 31549145
pii: 5573004
doi: 10.1093/gerona/glz209
pmc: PMC7457183
doi:
Substances chimiques
Biomarkers
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1558-1565Subventions
Organisme : NIA NIH HHS
ID : K24 AG045333
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG048234
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG023501
Pays : United States
Organisme : NIA NIH HHS
ID : K01 AG055698
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG032289
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG023481
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062422
Pays : United States
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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