Oxidative stress, inflammation and risk of neurodegeneration in a population sample

Background and purpose: Inflammation and oxidative stress (OS) have been clearly linked to neurodegeneration. However, studies investigating the associations between peripheral markers of inflammation and cognitive decline have produced mixed results. This is possibly due to the fact that markers are typically tested individually despite the fact that biologically they function interactively. Thus, the aim of this study was to investigate the association between a combination of OS/inflammation markers and outcomes including mild cognitive impairment (MCI) diagnosis, cognitive decline and hippocampal atrophy. Methods: Oxidative stress/inflammation status was assessed in 380 older community-living individuals. Thirteen blood markers were assayed. Principal component analysis (PCA) of all markers was conducted to identify the more salient inflammatory components. Associations between significant principal components, MCI diagnosis, previous change in Mini-Mental State Examination (MMSE) score and hippocampal atrophy were investigated through logistic and linear multiple regression. Results: Two factors (PC1 and PC2) reflecting predominantly broad pro-inflammatory activity and two factors (PC3 and PC4) reflecting predominantly OS activity were identified by PCA analysis. PC3 and PC4 were predictive of MCI. PC3 was also predictive of prior MMSE change. PC1, PC2 and PC3 were significantly associated with hippocampal atrophy. Conclusions: Combined analysis of complex and interacting biomarkers revealed a protective association between antioxidant activity and MCI that is consistent with lifestyle factors shown to reduce risk of cognitive decline. OS and broad systemic inflammation were also found to be associated with hippocampal atrophy further highlighting the benefits of the PCA methodology applied in this study.