Genetic Predisposition for Inflammation Exacerbates Effects of Striatal Iron Content on Cognitive Switching Ability in Healthy Aging

dc.contributor.ORCID0000-0001-5373-9026 (Kennedy, KM)
dc.contributor.authorDaugherty, Ana M.
dc.contributor.authorHoagey, David A.
dc.contributor.authorKennedy, Kristen M.
dc.contributor.authorRodrigue, Karen M.
dc.contributor.utdAuthorHoagey, David A.
dc.contributor.utdAuthorKennedy, Kristen M.
dc.contributor.utdAuthorRodrigue, Karen M.
dc.date.accessioned2020-09-22T19:48:08Z
dc.date.available2020-09-22T19:48:08Z
dc.date.issued2018-10-25
dc.description.abstractNon-heme iron homeostasis interacts with inflammation bidirectionally, and both contribute to age-related decline in brain structure and function via oxidative stress. Thus, individuals with genetic predisposition for inflammation may be at greater risk for brain iron accumulation during aging and more vulnerable to cognitive decline. We examine this hypothesis in a lifespan sample of healthy adults (N = 183, age 20 - 94 years) who underwent R2*-weighted magnetic resonance imaging to estimate regional iron content and genotyping of interleukin-1beta (IL-1β), a pro-inflammatory cytokine for which the T allelle of the single nucleotide polymorphism increases risk for chronic neuroinflammation. Older age was associated with greater striatal iron content that in turn accounted for poorer cognitive switching performance. Heterozygote IL-1β T-carriers demonstrated poorer switching performance in relation to striatal iron content as compared to IL-1β C/C counterparts, despite the two groups being of similar age. With increasing genetic inflammation risk, homozygote IL-1β T/T carriers had lesser age-related variance in striatal iron content as compared to the other groups but showed a similar association of greater striatal iron content predicting poorer cognitive switching. Non-heme iron and inflammation, although necessary for normal neuronal function, both promote oxidative stress that when accumulated in excess, drives a complex mechanism of neural and cognitive decline in aging.
dc.description.departmentSchool of Behavioral and Brain Sciences
dc.description.departmentCenter for Vital Longevity
dc.description.sponsorshipNational Institutes of Health: R00 AG-03618, R00 AG-03648 and R01 AG-056535; Alzheimer's Association grant NIRG-397220
dc.identifier.bibliographicCitationDaugherty, Ana M., David A. Hoagey, Kristen M. Kennedy, and Karen M. Rodrigue. 2019. "Genetic predisposition for inflammation exacerbates effects of striatal iron content on cognitive switching ability in healthy aging." Neuroimage 185: 471-478, doi: 10.1016/j.neuroimage.2018.10.064
dc.identifier.issn1053-8119
dc.identifier.urihttps://dx.doi.org/10.1016/j.neuroimage.2018.10.064
dc.identifier.urihttps://hdl.handle.net/10735.1/8916
dc.identifier.volume185
dc.language.isoen
dc.publisherAcademic Press Inc Elsevier Science
dc.rightsCC BY-NC-ND 4.0 (Attribution-NonCommercial-NoDerivatives)
dc.rights©2018 The Authors
dc.source.journalNeuroimage
dc.subjectAging
dc.subjectIron
dc.subjectInflammation
dc.subjectStructural equation modeling
dc.subjectAlzheimer's disease
dc.subjectOlder people
dc.subjectInterleukin-1
dc.subjectCytokines
dc.subjectNeurosciences
dc.subjectNeurology
dc.subject.meshAlzheimer Disease
dc.titleGenetic Predisposition for Inflammation Exacerbates Effects of Striatal Iron Content on Cognitive Switching Ability in Healthy Aging
dc.type.genrearticle

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