Long-term effects of electronic cigarettes on brain health

ABSTRACT Electronic cigarettes (e-cigs) are being touted as safer alternatives to traditional cigarettes, which have well- known harmful effects on the brain due to combustion-related inflammation and oxidative stress. Some smokers report using e-cigs to help quit smoking and switch to exclusive e-cig use. However, nicotine itself, as well as the other components of e-cig vapor, produce inflammation and oxidative stress, albeit to a lesser extent than traditional cigarettes. The effects of long-term e-cig use on the brain are poorly understood. Smoking cessation is associated with improvements in brain structure and function that correlate with quit duration, suggesting a recovery from the harmful effects of smoking. But whether switching from cigarettes to e-cigs results in comparable brain health is unknown. Most research on the health effects of e-cigs has been on short-term effects and/or use in adolescents and young adults compared to healthy non-users. Adult smokers are now the target of e-cig marketing and are being encouraged to make the switch to e-cigs. Research on the long-term, relative safety of e-cigs in this population is desperately needed. Existing research indicates smoking negatively affects brain measures, including gray matter volume (GMV), white matter integrity (WMI), cerebral blood flow (CBF), and cognitive performance (CP). Evidence from ex-smokers indicates that quitting smoking leads to positive changes in brain measures. Smoking and e-cigs also negatively affect physiological measures, such as autonomic function and inflammation, which in turn affect the brain. The key problem is to what extent abstinence from cigarette smoke, compared to abstinence from chronic nicotine, affects brain and physiological health. An important biomarker of the heaviness and duration of cigarette smoke exposure is DNA methylation of the AHRR CpG site, which we have shown correlates with GMV, WMI, and CP among smokers and ex-smokers. We will investigate the relationship between the objective AHRR biomarker and brain/physiological measures among ex-smokers (Ex-Quit) and ex-smokers who switched to e-cigs (Ex-Ecig) (compared to smokers and never-smokers) to shed light on the relative harm of e-cigs. Smokers are increasingly relying on e-cigs to make a quit attempt; yet research on the long-term health effects of e-cigs (> 1 year of use) on adult ex-smokers is almost nonexistent. This study will expeditiously fill this critical gap in knowledge.