Influence of Lifestyle Modifications on Age-Related Free Radical Injury to Brain

Importance  The Healthy Brain Initiative 2013-2018 seeks to optimize brain health as we age. Free radical injury is an important effector of molecular and cellular stress in the aging brain that derives from multiple sources.

Objective  To identify potentially modifiable risk factors associated with increased markers of brain oxidative stress.

Design, Setting, and Participants  This cross-sectional, academic multicenter study consisted of 320 research volunteers (172 women) aged 21 to 100 years who were medically healthy and cognitively normal.

Main Outcomes and Measures  Free radical injury to the brain was assessed using cerebrospinal fluid (CSF) F2-isoprostane (F2-IsoP) concentrations correlated with age, sex, race, cigarette smoking, body mass index, inheritance of the ε4 allele of the apolipoprotein E gene (APOE), and CSF biomarkers of Alzheimer disease.

Results  The concentration of CSF F2-IsoP increased with age by approximately 3 pg/mL (approximately 10%) from age 45 to 71 years in medically healthy, cognitively normal adults (P < .001). The CSF F2-IsoP concentration increased by approximately more than 10% for every 5-U increase in body mass index (P < .001). Current smoking had an approximately 3-fold greater effect on CSF F2-IsoPs compared with age (P < .001). Women had greater mean CSF F2-IsoP concentrations than men at all ages after adjusting for other factors (P = .02). Neither the concentration of CSF Alzheimer disease biomarkers nor inheritance of the APOE ε4 allele was associated with the CSF F2-IsoP concentration in this group of medically healthy, cognitively normal adults (P > .05). The association between CSF F2-IsoP concentrations and race was not significant after controlling for the effect of current smoking status (P = .45).

Conclusions and Relevance  Our results are consistent with an age-related increase in free radical injury in the human brain and uniquely suggest that this form of injury may be greater in women than in men. Our results also highlighted 2 lifestyle modifications (ie, body mass index and smoking) that would have an even greater effect on suppressing free radical injury to the brain than would suppressing the processes of aging. These results inform efforts to achieve success in the Healthy Brain Initiative 2013-2018.

JAMA Neurology 2014