Longitudinal Assessments of Neurocognitive Performance and Brain Structure Associated With Initiation of Tobacco Use in Children, 2016 to 2021

Abstract

Importance: The landscape of tobacco use is changing. However, information about the association between early-age tobacco use and cognitive performances is limited, especially for emerging tobacco products such as electronic cigarettes (e-cigarettes).

Objective: To assess the association between early-age initiation of tobacco use and cognitive performances measured by the National Institutes of Health (NIH) Toolbox Cognitive Battery and to examine whether initiation is associated with differences in brain morphometry.

Design, setting, and participants: This observational cohort study examined the longitudinal associations of initiation of tobacco use with neurocognition using multivariate linear mixed models. Children aged 9 to 10 years from 21 US sites were enrolled in wave 1 (October 1, 2016, to October 31, 2018 [n = 11 729]) and the 2-year follow-up (August 1, 2018, to January 31, 2021 [n = 10 081]) of the Adolescent Brain Cognitive Development (ABCD) Study.

Exposures: Ever use (vs none) of any tobacco products at wave 1, including e-cigarettes, cigarettes, cigars, smokeless tobacco, hookah, pipes, and nicotine replacement.

Main outcomes and measures: Neurocognition measured by the NIH Toolbox Cognition Battery and morphometric measures of brain structure and region of interest analysis for the cortex from structural magnetic resonance imaging.

Results: Among 11 729 participants at wave 1 (mean [SE] age, 9.9 [0.6] years; 47.9% girls and 52.1% boys; 20.3% Hispanic; 14.9% non-Hispanic Black; and 52.1% non-Hispanic White), 116 children reported ever use of tobacco products. Controlling for confounders, tobacco ever users vs nonusers exhibited lower scores in the Picture Vocabulary Tests at wave 1 (b [SE] = -2.9 [0.6]; P < .001) and 2-year follow-up (b [SE] = -3.0 [0.7]; P < .001). The crystalized cognition composite score was lower among tobacco ever users than nonusers both at wave 1 (b [SE] = -2.4 [0.5]; P < .001) and 2-year follow-up (b [SE] = -2.7 [0.8]; P = .005). In structural magnetic resonance imaging, the whole-brain measures in cortical area and volume were significantly lower among tobacco users than nonusers, including cortical area (b [SE] = -5014.8 [1739.8] mm2; P = .004) at wave 1 and cortical volume at wave 1 (b [SE] = -174 621.0 [5857.7] mm3; P = .003) and follow-up (b [SE] = -21 790.8 [7043.9] mm3; P = .002). Further region of interest analysis revealed smaller cortical area and volume in multiple regions across frontal, parietal, and temporal lobes at both waves.

Conclusions and relevance: In this cohort study, initiating tobacco use in late childhood was associated with inferior cognitive performance and reduced brain structure with sustained effects at 2-year follow-up. These findings suggest that youths vulnerable to e-cigarettes and tobacco products should be treated as a priority population in tobacco prevention.

Figure 1.. Flowchart of Analytical Sample Inclusion and Exclusion From the Adolescent Brain Cognitive Development (ABCD) Study

The selection procedure was based on the protocols in previous studies and the ABCD Study magnetic resonance imaging quality control guideline.^, NIH indicates National Institutes of Health.

Figure 2.. Differential Brain Structures Associated With Initiation of Tobacco Use in Childhood

Cortical surface measurements include 15 clusters at baseline and 10 clusters at 2-year follow-up. Cortical volume measurements include 17 clusters at baseline and 2-year follow-up. Brain structures significantly associated with early initiation of tobacco use (false discovery rate <0.05) are labeled by T values of cortical area and volume between ever tobacco users and nonusers, adjusted by age, sex, race and ethnicity, pubertal stage, substance ever use, parental monitoring, school environment, handedness, imaging device manufacturer, and study site. cACG indicates caudal anterior cingulate gyrus; cMFG, caudal middle frontal gyrus; FG, fusiform gyrus; iCG, isthmus cingulate; Ins, insula; lOFG, lateral orbitofrontal gyrus; mOFG, medial orbitofrontal gyrus; MTG, middle temporal gyrus; IPL, inferior parietal lobule; PCG, paracentral gyrus; PhG, parahippocampal gyrus; pOrIFG, pars orbitalis; PostCG, postcentral gyrus; PreCG, precentral gyrus; PreCu, precuneus; rACG, rostral anterior cingulate gyrus; rMFG, rostral middle frontal gyrus; SFG, superior frontal gyrus; SMG, supramarginal gyrus; STG, superior temporal gyrus; and STS, banks of superior temporal sulcus.