Structural brain changes and all-cause mortality in the elderly population-the mediating role of inflammation.

Abstract

While MRI brain changes have been relatedto mortality during ageing, the role of inflammation in this relationship remains poorly understood. Hence, this study aimed to investigate the impact of MRI changes on all-cause mortality and the mediating role of cytokines. All-cause mortality was evaluated in 268 community dwelling elderly (age 65-83years) in the MEMO study (Memory and Morbidity in Augsburg elderly). MRI markers of brain atrophy and cerebral small vessel disease (SVD), C-reactive protein(CRP) and a panel of cytokines in serum were assessed. Cox proportional hazard models were used to estimate the association of MRI changes with survival over 9years. Regression models were used to assess the hypothesis that inflammation is mediating the relationship between MRI-brain changes and mortality. In total, 77 (29%) deaths occurred during a mean follow up of 9years. After adjusting for confounders, the degree of global cortical atrophy and the level of the cytokines CRP, TNF-α and IL-8 were of higher significance in study participants who had died at follow-up in comparison to survivors. In Cox proportional hazard models, higher degrees of global cortical atrophy (HR 1.56, p=0.003) and regional atrophy of the temporal lobe (HR 1.38, p=0.011) were associated with a significantly increased risk of mortality. Mediation analyses revealed a partial mediation by IL-6 and IL-8 of the effects of global cortical atrophy on mortality. Global cortical brain atrophy is a significant indicator of survival in the elderly. Our study supports a possible role for inflammation in the atrophy pathogenesis. If replicated in other samples, IL-6 and IL-8 level assessment may improve risk prognosis for mortality.