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Neuroimage. 2018 May 15;172:118-129. doi: 10.1016/j.neuroimage.2017.12.027. Epub 2018 Jan 28.

Systemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk.

Author information

1
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA 90292, USA.
2
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
3
Departments of Neurology, Psychiatry, and Psychology, University of Pittsburgh, Pittsburgh, PA 15139, USA.
4
Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
5
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA 90292, USA; Depts. of Neurology, Psychiatry, Engineering, Radiology, & Ophthalmology, Keck/USC School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
6
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA 90292, USA. Electronic address: meredith.braskie@ini.usc.edu.

Abstract

Inflammatory processes may contribute to risk for Alzheimer's disease (AD) and age-related brain degeneration. Metabolic and genetic risk factors, and physical activity may, in turn, influence these inflammatory processes. Some of these risk factors are modifiable, and interact with each other. Understanding how these processes together relate to brain aging will help to inform future interventions to treat or prevent cognitive decline. We used brain magnetic resonance imaging (MRI) to scan 335 older adult humans (mean age 77.3 ± 3.4 years) who remained non-demented for the duration of the 9-year longitudinal study. We used structural equation modeling (SEM) in a subset of 226 adults to evaluate whether measures of baseline peripheral inflammation (serum C-reactive protein levels; CRP), mediated the baseline contributions of genetic and metabolic risk, and physical activity, to regional cortical thickness in AD-relevant brain regions at study year 9. We found that both baseline metabolic risk and AD risk variant apolipoprotein E ε4 (APOE4), modulated baseline serum CRP. Higher baseline CRP levels, in turn, predicted thinner regional cortex at year 9, and mediated an effect between higher metabolic risk and thinner cortex in those regions. A higher polygenic risk score composed of variants in immune-associated AD risk genes (other than APOE) was associated with thinner regional cortex. However, CRP levels did not mediate this effect, suggesting that other mechanisms may be responsible for the elevated AD risk. We found interactions between genetic and environmental factors and structural brain health. Our findings support the role of metabolic risk and peripheral inflammation in age-related brain decline.

KEYWORDS:

AD; Alzheimer's disease; Brain structure; Brain volume; C-reactive protein; CRP; Cholesterol; Cognitive aging; Cortical thickness; Gene; Genetic risk; Inflammation; Insulin; Metabolic risk; Neuroinflammation; Obesity; Physical activity; Polygenic risk score

PMID:
29357308
PMCID:
PMC5954991
[Available on 2019-05-15]
DOI:
10.1016/j.neuroimage.2017.12.027

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