In vivo chronic cigarette smoke exposure is also associated with decreased enzyme-based free radical scavenger (e.g., superoxide dismutase, catalase, glutathione reductase) and non-enzyme-based radical scavenger (e.g., glutathione and vitamins A, C and E) concentrations in rat brains [132,133]. This may render brain tissue more vulnerable to oxidative damage by radical species generated by cellular metabolism or other exogenous sources. The brain, in general, is exceedingly susceptible to oxidative damage because of high levels of unsaturated fatty acids in the composition of cell membranes and myelin. Additionally, chronic cigarette smoking is related to nocturnal hypoxia [7] as well as chronic obstructive pulmonary disease and other conditions that may impair lung function [8]. Decreased lung function is associated with poorer neurocognition and increased subcortical atrophy in older adults [134]. Chronic smoking increases the risk for atherosclerosis [9], as well as abnormalities in vascular endothelial morphology and function [135–138], which may alter cerebral perfusion. Additionally, nicotine administered through means other than cigarette smoke may alter or impair vasomotor reactivity of cerebral arterioles through upregulation of Ca2+ channels and/or modulation of nitric oxide [136].
