- Lindbergh, Cutter A;
- Casaletto, Kaitlin B;
- Staffaroni, Adam M;
- Elahi, Fanny;
- Walters, Samantha M;
- You, Michelle;
- Neuhaus, John;
- Contreras, Will Rivera;
- Wang, Paul;
- Karydas, Anna;
- Brown, Jesse;
- Wolf, Amy;
- Rosen, Howie;
- Cobigo, Yann;
- Kramer, Joel H
- Editor(s): Newman, Anne
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.