Cognitive Decline Is Associated with Systemic Oxidative Stress: The EVA Study

Abstract

OBJECTIVE: To determine whether systemic oxidative stress status is associated with cognitive decline. DESIGN: A longitudinal population-based study. SETTING: A cohort study of older subjects in Nantes, France. PARTICIPANTS: A total of 1166 high cognitive functioning subjects aged 60 to 70 in the Etude du Vieillissement Arteriel (EVA) cohort with a 4 year follow-up. MEASUREMENTS: Subjects completed a baseline interview and a global cognitive test (Mini-Mental Status Examination (MMSE)). Blood samples were obtained at baseline to determine plasma levels of selenium, carotenoids, thiobarbituric acid reactant substances (TBARS), an indicator of lipoperoxidation, and red blood cell vitamin E. Risk of cognitive decline, defined as a loss of 3 points in MMSE score between baseline and the 4 year follow-up, was assessed by oxidative stress level. RESULTS: Subjects with the highest levels of TBARS show an increased risk of cognitive decline (adjusted odds ratio (OR) = 2.25; confidence interval (CI) 95% = 1.26-4.02). This result is reinforced in the lower antioxidant status subgroup. Subjects with low levels of selenium have an increased risk of cognitive decline (OR = 1.58; CI 95% = 1.08-2.31) after adjustment for various confounding factors. CONCLUSIONS: These results suggest that increased levels of oxidative stress and/or antioxidant deficiencies may pose risk factors for cognitive decline. The direct implication of oxidative stress in vascular and neurodegenerative mechanisms that lead to cognitive impairment should be further explored.