Background Cigarette smoking has been linked with both increased and decreased risk for Alzheimer’s disease (AD). This is relevant for the US military because the prevalence of smoking in the military is approximately 11% higher than in civilians. Methods Systematic review of published studies on the association between smoking and increased risk for AD, and preclinical and human literature on the relationships between smoking, nicotine exposure and AD-related neuropathology. Original data from comparisons of smoking and never-smoking cognitively normal elders on in vivo amyloid imaging are also presented. Results Overall, the literature indicates that former/active smoking is related to a significantly increased risk for AD. Cigarette smoke/smoking is associated with AD neuropathology in preclinical models and humans. Smoking-related cerebral oxidative stress is a potential mechanism promoting AD pathophysiology and increased risk for AD. Conclusions A reduction in the incidence of smoking will likely reduce the future prevalence of AD.

BACKGROUND At least 60% of those treated for an alcohol use disorder will relapse. Empirical study of the integrity of the brain reward system (BRS) is critical to understanding the mechanisms of relapse as this collection of circuits is implicated in the development and maintenance of all forms of addictive disorders. This study compared thickness, surface area and volume in neocortical components of the BRS among non-smoking light drinking controls (Controls), individuals who remained abstinent and those who relapsed after treatment. METHODS Seventy-five treatment-seeking alcohol dependent individuals (abstinent for 7 ± 3 days) and 43 Controls completed 1.5T proton magnetic resonance imaging studies. Parcellated morphological data was obtained for following bilateral components of the BRS: rostral and caudal anterior cingulate cortex, insula, medial and lateral orbitofrontal cortex, rostral and caudal middle and superior frontal gyri, amygdala and hippocampus as well as for 26 other bilateral neocortical regions. Alcohol dependent participants were followed over 12-months after baseline study and were classified as Abstainers (no alcohol consumption; n=24) and Relapsers (any alcohol consumption; n=51) at follow-up. RESULTS Relapsers and Abstainers demonstrated lower cortical thickness in the vast majority of BRS regions as well as lower global thickness compared to Controls. Relapsers had lower total BRS surface area than both Controls and Abstainers, but Abstainers were not significantly different from Controls on any surface area measure. Relapsers demonstrated lower volumes than Controls in the majority of regions, while Abstainers showed lower volumes than Controls in the superior frontal gyrus, insula, amygdala and hippocampus, bilaterally. Relapsers exhibited smaller volumes than Abstainers in the right rostral middle and caudal middle frontal gyri and the lateral orbitofrontal cortex, bilaterally. In Relapsers, lower baseline volumes and surface areas in multiple regions were associated with a greater magnitude of post-treatment alcohol consumption. CONCLUSIONS Results suggest Relapsers demonstrated morphological abnormalities in regions involved in the “top down” regulation/modulation of internal drive states, emotions, reward processing and behavior, which may impart increased risk for the relapse/remit cycle that afflicts many with an AUD. Results also highlight the importance of examining both cortical thickness and surface area to better understand the nature of regional volume loss frequently observed in AUD. Results from this report are consistent with previous research implicating plastic neurobiological changes the brain reward system in the maintenance of addictive disorders.

Compared to the substantial volume of research on the general health consequences associated with chronic smoking, little research has been specifically devoted to the investigation of its effects on human neurobiology and neurocognition. This review summarizes the peer-reviewed literature on the neurocognitive and neurobiological implications of chronic cigarette smoking in cohorts that were not seeking treatment for substance use or psychiatric disorders. Studies that specifically assessed the neurocognitive or neurobiological (with emphasis on computed tomography and magnetic resonance-based neuroimaging studies) consequences of chronic smoking are highlighted. Chronic cigarette smoking appears to be associated with deficiencies in executive functions, cognitive flexibility, general intellectual abilities, learning and/or memory processing speed, and working memory. Chronic smoking is related to global brain atrophy and to structural and biochemical abnormalities in anterior frontal regions, subcortical nuclei and commissural white matter. Chronic smoking may also be associated with an increased risk for various forms of neurodegenerative diseases. The existing literature is limited by inconsistent accounting for potentially confounding biomedical and psychiatric conditions, focus on cross-sectional studies with middle aged and older adults and the absence of studies concurrently assessing neurocognitive, neurobiological and genetic factors in the same cohort. Consequently, the mechanisms promoting the neurocognitive and neurobiological abnormalities reported in chronic smokers are unclear. Longitudinal studies are needed to determine if the smoking-related neurobiological and neurocognitive abnormalities increase over time and/or show recovery with sustained smoking cessation.