02476nas a2200229   4500008004100000022001400041245012700055210006900182260001600251300001200267490000800279520175100287100002002038700002102058700002202079700002102101700002102122700002002143700002202163700002502185856003602210       2018                        eng d  a1095-957200aSystemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk.0 aSystemic inflammation as a predictor of brain aging Contribution  c2018 May 15  a118-1290 v1723 a<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>1 aCorlier, Fabian1 aHafzalla, George1 aFaskowitz, Joshua1 aKuller, Lewis, H1 aBecker, James, T1 aLopez, Oscar, L1 aThompson, Paul, M1 aBraskie, Meredith, N  uhttps://chs-nhlbi.org/node/7676