Neuroinflammation-associated thalamocortical functional connectivity and cognition in older adults.

Authors

Jeffrey Browndyke, Tyler Reekes, Mary C Wright, Melody R Smith, Michael Devinney, Piper Boykin, Vinith R Upadhya, Daphne Zhu, Katherine T Martucci, Leslie M Shaw, Teresa Waligorska, Charlotte Herber, Connie Tian Yu, Henrik Zetterberg, Kaj Blennow, Janet L Huebner, Harvey J Cohen, Heather Whitson, Joseph P Mathew, Miles Berger, INTUIT & MADCO-PC Trial Investigators

Published in

Journal of neuroinflammation. Volume 23. Issue 1. Aug 01, 2026. Epub Aug 01, 2026.

Abstract

Neuroinflammation has detrimental neurocognitive effects in patients with systemic and neuropsychiatric diseases. Yet, outside of these conditions, it is unclear to what extent neuroinflammation modulates brain network-level function in older adults in the general population and, what, if any cognitive performance issues arise as a result. To evaluate these questions, we compared cerebrospinal fluid (CSF) inflammatory cytokine levels, resting-state functional magnetic resonance imaging, and cognitive performance data in 96 community-dwelling older adults (age ≥ 60 yrs). Principal component analysis yielded three components, accounting for > 50% of the variance in CSF cytokine levels; of which, the first principal component (PC1) accounted for 32% of the overall variance. A multivariate pattern analysis regression model, adjusted for age, sex and in-scanner movement, revealed cytokine PC1 values were inversely associated with functional connectivity between the mediodorsal thalamus and multiple cortical regions associated with the frontoparietal, default mode and dorsal attention functional brain networks (p-FWE = 0.037). For the majority of these cortical regions, functional connectivity with the mediodorsal thalamus was not associated with cognitive performance. In a robust multivariable model, narrative memory performances were positively associated with thalamocortical connectivity to a posterior parietal hub region of the frontoparietal and dorsal attention networks [beta = 0.25 (95% CI; 0.01, 0.49); p = 0.040], but this association did not survive correction for the number of evaluated cognitive domains (Bonferroni-adjusted p < 0.01). Study results reveal that neuroinflammatory CSF cytokine levels were inversely associated with functional connectivity between the mediodorsal thalamus and cortical regions largely involved in frontoparietal, dorsal attention and default mode networks, but the functional consequences of this relationship remain to be determined and will require further investigation to determine if reduced corticothalamic functional connectivity may help account, in part, for common illness-related cognitive complaints.

PMID:
42732056
Bibliographic data and abstract were imported from PubMed on 13 Sep 2026.

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