Abstract
Peripheral inflammation has been implicated in cognitive dysfunction and dementia. While studies outline the relationship between elevated inflammation and individual gray or white matter alterations, less work has examined inflammation as related to connectivity between gray and white matter or variability in these associations by race. We examined the relationship between peripheral inflammation and tract-based structural connectomics in 74 non-demented participants (age = 69.19 ± 6.80 years; 53% female; 45% Black) who underwent fasting venipuncture and MRI. Serum was assayed for C-reactive protein, interleukin-6, and interleukin-1β. Graph theory analysis integrated T1-derived gray matter volumes and DTI-derived white matter tractography into connectivity matrices analyzed for local measures of nodal strength and efficiency in a priori regions of interest associated with cardiovascular disease risk factors and dementia. Linear regressions adjusting for relevant covariates showed associations between inflammatory markers and nodal strength in the isthmus, posterior and caudal anterior cingulate (p’s ≤ .042). Adding an inflammatory marker*race term showed race-modified associations between C-reactive protein and efficiency in the thalamus and amygdala, and nodal strength in the putamen (p’s ≤ .048), between interleukin-6 and efficiency in the pars triangularis and amygdala (p’s ≤ .024), and between interleukin-1β and nodal strength in the pars opercularis (p = .048). Higher levels of inflammation associated with lower efficiency and higher strength for White participants but higher efficiency and lower strength for Black participants. Results suggest inflammation is associated with tract-based structural connectomics in an older diverse cohort and that differential relationships may exist by race within prefrontal and limbic brain regions.
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The authors would like to thank the participants of this study and all prior research assistants for their help collecting data.
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Research was supported by the National Institute on Aging at the National Institutes of Health (K01 AG040192, R21 AG048176). Ms. Boots was further supported by F31 AG064829; Dr. Barnes was further supported by R01 AG056405.
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Author contributions included conception and study design (EAB, ML), data collection or acquisition (EAB, KJC, LTH, ML), statistical analysis (EAB, LZ, and ML), interpretation of results (EAB, LZ, LLB, LTH, ML), drafting the manuscript work or revising it critically for important intellectual content (all authors), and approval of final version to be published and agreement to be accountable for the integrity and accuracy of all aspects of the work (all authors).
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Boots, E.A., Zhan, L., Castellanos, K.J. et al. Inflammatory markers and tract-based structural connectomics in older adults with a preliminary exploration of associations by race. Brain Imaging and Behavior 16, 130–140 (2022). https://doi.org/10.1007/s11682-021-00483-y
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DOI: https://doi.org/10.1007/s11682-021-00483-y