Smoking alters effective connectivity of resting-state brain networks in mild cognitive impairment

BackgroundSmoking, a modifiable risk factor for Alzheimer's disease (AD), is associated with impaired functional connectivity in resting-state networks (RSNs). This study investigates how smoking affects brain effective connectivity (EC).ObjectiveInvestigate smoking-associated EC alterations.MethodsWe identified 129 cognitively unimpaired (CU: 85 non-smokers, 44 smokers) and 84 mild cognitive impairment (MCI: 55 non-smokers, 29 smokers) participants. Granger causality analysis was used to calculate the directed interactions of information flows based on the seed areas of the default mode network, executive control network, and salience network. Mixed-effect analyses were performed to explore the interactive effects of smoking × cognitive status. Linear mixed-effects models evaluated correlations between EC values and longitudinal cognitive decline.ResultsMixed-effect analyses revealed significant interactive EC differences among 4 groups: (1) Smoking MCI individuals showed reduced EC from the left putamen to the frontoinsular cortex (FIC) compared to the smoking CU and non-smoking MCI group; (2) Non-smoking MCI subjects had lower EC from the dorsolateral prefrontal cortex (DLPFC) to the right inferior occipital gyrus (IOG) than non-smoking CU; (3) Smoking CU subjects exhibited increased EC from the DLPFC to the left middle cingulate cortex compared to the with the non-smoking CU and smoking MCI individuals. Additionally, EC_{Posterior cingulate cortex-to-IOG} and EC_{Putamen-to-FIC} significantly predicted MMSE and ADNI_EF scores over time, respectively.ConclusionsSmoking distinctly impacts EC within RSNs and overall brain function in both MCI and CU individuals, potentially reducing functional compensation in MCI. These results support smoking cessation as part of AD management strategies.