Active Cigarette Smoking in Cognitively-Normal Elders and Probable Alzheimer’s Disease is Associated with Elevated Cerebrospinal Fluid Oxidative Stress Biomarkers

Abstract

Neurodegenerative diseases and chronic cigarette smoking are associated with increased cerebral oxidative stress (OxS). Elevated F₂-isoprostane levels in biological fluid is a recognized marker of OxS. This study assessed the association of active cigarette smoking with F₂-isoprostane in concentrations in cognitively-normal elders (CN), and those with mild cognitive impairment (MCI) and probable Alzheimer’s disease (AD). Smoking and non-smoking CN (n = 83), MCI (n = 164), and probable AD (n = 101) were compared on cerebrospinal fluid (CSF) iPF_2α-III and 8,12, iso-iPF_2α-VI F₂-isoprostane concentrations. Associations between F₂-isoprostane levels and hippocampal volumes were also evaluated. In CN and AD, smokers had higher iPF_2α-III concentration; overall, smoking AD showed the highest iPF_2α-III concentration across groups. Smoking and non-smoking MCI did not differ on iPF_2α-III concentration. No group differences were apparent on 8,12, iso-iPF_2α-VI concentration, but across AD, higher 8,12, iso-iPF_2α-VI level was related to smaller left and total hippocampal volumes. Results indicate that active cigarette smoking in CN and probable AD is associated with increased central nervous system OxS. Further investigation of factors mediating/moderating the absence of smoking effects on CSF F₂-isoprostane levels in MCI is warranted. In AD, increasing magnitude of OxS appeared to be related to smaller hippocampal volume. This study contributes additional novel information to the mounting body of evidence that cigarette smoking is associated with adverse effects on the human central nervous system across the lifespan.