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Background:  Mild cognitive impairment (MCI) is the prodromal phase of Alzheimer’s disease (AD) and has a high risk of progression to AD. Cigarette smoking is one of the important modifiable risk factors in AD progression. Cholinergic dysfunction, especially the nucleus basalis of Meynert (NBM), is the converging target connecting smoking and AD. However, how cigarette smoking affects NBM connectivity in MCI remains unclear.   Objective:  This study aimed to evaluate the interaction effects of condition (non-smoking vs. smoking) and diagnosis [cognitively normal (CN) vs. MCI] based on the resting-state functional connectivity (rsFC) of the NBM.   Methods:  After propensity score matching, we included 86 non-smoking CN, 44 smoking CN, 62 non-smoking MCI, and 32 smoking MCI. All subjects underwent structural and functional magnetic resonance imaging scans and neuropsychological tests. The seed-based rsFC of the NBM with the whole-brain voxel was calculated. Furthermore, the mixed effect analysis was performed to explore the interaction effects between condition and diagnosis on rsFC of the NBM.   Results:  The interaction effects of condition × diagnosis on rsFC of the NBM were observed in the bilateral prefrontal cortex (PFC), bilateral supplementary motor area (SMA), and right precuneus/middle occipital gyrus (MOG). Specifically, the smoking CN showed decreased rsFC between left NBM and PFC and increased rsFC between left NBM and SMA compared with non-smoking CN and smoking MCI. The smoking MCI showed reduced rsFC between right NBM and precuneus/MOG compared with non-smoking MCI. Additionally, rsFC between the NBM and SMA showed a significant negative correlation with Wechsler Memory Scale-Logical Memory (WMS-LM) immediate recall in smoking CN ( r  = −0.321,  p  = 0.041).   Conclusion:  Our findings indicate that chronic nicotine exposure through smoking may lead to functional connectivity disruption between the NBM and precuneus in MCI patients. The distinct alteration patterns on NBM connectivity in CN smokers and MCI smokers suggest that cigarette smoking has different influences on normal and impaired cognition.

Effects of Cigarette Smoking on Resting-State Functional Connectivity of the Nucleus Basalis of Meynert in Mild Cognitive Impairment