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

TitleSystemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk.
Publication TypeJournal Article
Year of Publication2018
AuthorsCorlier, F, Hafzalla, G, Faskowitz, J, Kuller, LH, Becker, JT, Lopez, OL, Thompson, PM, Braskie, MN
JournalNeuroimage
Volume172
Pagination118-129
Date Published2018 May 15
ISSN1095-9572
Abstract<p>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.</p>
DOI10.1016/j.neuroimage.2017.12.027
Alternate JournalNeuroimage
PubMed ID29357308
Grant ListRF1 AG041915 / AG / NIA NIH HHS / United States
P50 AG005142 / AG / NIA NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
R01 AG040060 / AG / NIA NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
ePub date: 
18/01