Interaction of Cigarette Smoking History With APOE Genotype and Age on Amyloid Level, Glucose Metabolism, and Neurocognition in Cognitively Normal Elders.

INTRODUCTION: Chronic cigarette smoking is associated with increased risk for Alzheimer's disease (AD). The goal of this study was to determine if smoking history moderated the associations of age and APOE genotype (the most robust risk factors for AD) on brain amyloid deposition, glucose metabolism, and neurocognition in cognitively-normal elders.
METHODS: Participants (n = 264) were grouped according to their APOE ε4 carrier status (ε4 carrier: APOE4+; non-ε4 carrier: APOE4-) and smoking status (smokers: at least 1 year of smoking during lifetime; never-smokers: no history of smoking). Approximately 89% of the smoking sample was former-smokers. We specifically tested for interactions of smoking status with APOE ε4 carrier status and age on measures of cortical amyloid deposition, glucose metabolism, and neurocognition.
RESULTS: (1) smoking status interacted with APOE ε4 carrier status, where smoker APOE4+ showed lower glucose metabolism and poorer auditory-verbal learning and memory than never-smoking APOE4-, never-smoking APOE4+, and smoking APOE4-; (2) smoking status interacted with age on measures of semantic fluency, processing speed/set-shifting and global neurocognition; smokers, irrespective of APOE ε4 carrier status, demonstrated poorer performance with increasing age than never-smokers; and (3) smoking APOE4+ and never-smoking APOE4+ showed greater cortical amyloid deposition than never-smoking APOE4- and smoking APOE4-.
CONCLUSIONS: The findings indicate consideration of smoking history is essential to both better understand the factors associated with neurobiological and neurocognitive abnormalities in elders, and the risk for development of AD-related neuropathology.