Oxidative stress (OS) and inflammation are processes known to be implicated in neurodegeneration. Moreover, risk factors for dementia (depression, obesity, sedentary lifestyle, diabetes, etc.) are associated with up-regulation of pro-inflammatory cytokines. OS has been found in animal models to contribute to cerebral amyloid angiopathy. However, investigations of the associations between OS, inflammation and MCI, typically in small clinical samples have produced mixed results.

Clarify associations, between OS, inflammation and MCI in a large cohort of community-living individuals.

Cognitively healthy individuals (n = 211, 44% female, 75.2 years) and with MCI (n = 23, 44% female, 75.2 years) from a population sample were included. MCI diagnosis was established based on a detailed neuropsychological assessment. Inflammatory (IL1b, IL4, IL6, IL8, IL10, TNF-a) and OS (total anti-oxidants, NO, neopterin) markers were assessed in plasma samples. Associations between biomarkers, MMSE, and MCI status were tested with multiple linear and logistic regression analyses.

Univariate analyses showed that log IL4 (estimate: −0.175, SE: 0.085, P = 0.041) and NO (estimate: 0.015, SE: 0.006, P = 0.017) were the only markers associated with MMSE scores. MCI status was predicted by log IL4 (estimate: 0.822, SE: 0.357, P = 0.021) and total anti-oxidants (estimate: −0.007, SE: 0.003, P = 0.014). Controlling for pro-inflammatory conditions (T2D, BMI, depression, hypertension) removed the associations with inflammation but not with OS.

These results indicate that increased systemic inflammation and increased OS were associated with lower MMSE scores and higher odds of having MCI. This confirms that systemic pro-inflammatory processes are associated with impaired cognition and should be specifically considered in treatment and risk-reduction interventions.

The authors have not supplied their declaration of competing interest.