Brain morphology links systemic inflammation to cognitive function in midlife adults
Open accessAbstract
Background Inflammation is linked to cognitive decline in midlife, but the neural basis for this link is unclear. One possibility is that inflammation associates with adverse changes in brain morphology, which accelerates cognitive aging and later dementia risk. Clear evidence is lacking, however, regarding whether inflammation relates to cognition in midlife via changes in brain morphology. Accordingly, the current study examines whether associations of inflammation with cognitive function are mediated by variation in cortical gray matter volume among midlife adults. Methods Plasma levels of interleukin (IL)-6 and C-reactive protein (CRP), relatively stable markers of peripheral systemic inflammation, were assessed in 408 community volunteers aged 30-54 years. All participants underwent structural neuroimaging to assess global and regional brain morphology and completed neuropsychological tests sensitive to early changes in cognitive function. Measurements of brain morphology (regional tissue volumes and cortical thickness and surface area) were derived using Freesurfer. Results Higher peripheral inflammation was associated with poorer spatial reasoning, short term memory, verbal proficiency, learning and memory, and executive function, as well as lower cortical gray and white matter volumes, hippocampal volume and cortical surface area. Mediation models with age, sex and intracranial volume as covariates showed cortical gray matter volume to partially mediate the association of inflammation with cognitive performance. Exploratory analyses of body mass suggested that adiposity may be a source of the inflammation linking brain morphology to cognition. Conclusions Inflammation and adiposity might relate to cognitive decline via influences on brain morphology.
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Correlational research links mildly elevated inflammatory markers to cognitive function measured both by self-report and objectively.
“In some ways, this is puzzling given that inflammatory processes have been shown to regulate learning and memory (e.g., Yirmiya and Goshen, 2011) and that correlational studies have identified associations between mild elevations in inflammatory markers and both self-reported (Davis et al., 2018; Kuhlman et al., 2018) and objective (Marsland et al., 2015) measures of cognitive function.”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Marsland et al., 2015
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Clinical Phenotype of Depression Affects Interleukin-6 Synthesis
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- Authors
- Marsland, A. L., Gianaros, P. J., Kuan, D. C.-H., Sheu, L. K., Krajina, K., & Manuck, S. B.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Marsland, Anna L.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 48
- Pages
- 195-204
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC4508197
- OpenAlex
- W1993608602
- Cited by
- 321
- References
- 107
- Citations by year
- 2026: 33 · 2025: 39 · 2024: 27 · 2023: 35 · 2022: 31 · 2021: 39 · 2020: 31 · 2019: 26 · 2018: 25 · 2017: 18 · 2016: 11 · 2015: 5 · 2014: 1
- FWCI
- 15.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000005)
- National Heart, Lung, and Blood Institute (R01HL089850, P01HL040962)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- systemic inflammation, cognitive function, brain structure, cortical gray matter volume, interleukin-6, C-reactive protein, middle-aged adults, mediation, hippocampal volume, cortical surface area, adiposity, cognitive aging, dementia risk, executive function, memory
- MeSH terms
- Adult, Brain, C-Reactive Protein, Cognition, Female, Humans, Inflammation, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Organ Size, Interleukin-6, Executive Function, Neuroimaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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