Beyond the Percentile: CDC-referenced BMI-for-Age and Brain Structure Across Childhood and Adolescence
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Importance
Pediatric obesity affects 1 in 5 US children and has been linked to brain structural differences. Most evidence is cross-sectional and models body mass index (BMI) linearly, with metrics that compress severe obesity.
Objective
To examine associations between brain structure and BMI-for-age across the weight spectrum and Centers for Disease Control and Prevention (CDC) weight status categories, distinguishing between- and within-person associations, and their age and sex moderation.
Design, Setting, and Participants
Longitudinal cohort study of youth aged 8–10 years at baseline in the US community-based Adolescent Brain Cognitive Development Study (4 waves, 2016–2025; ages 8–18 years).
Exposures
Extended CDC BMI-for-age z-score, grouped by wave-mean z-score: underweight (<5th percentile, n=297), healthy weight (5th–<85th, n=7,452), overweight (85th–<95th, n=1,919), and obesity (≥95th, n=1,842).
Main Outcomes and Measures
Cortical thickness (12 regions) and subcortical volume (7 regions) from T1-weighted magnetic resonance imaging (MRI), defined a priori.
Results
Among 11,510 participants contributing 32,212 observations (mean [SD] age, 12.6 [2.5] years; 52.2% male), higher between-person BMI-for-age z was associated with lower frontal and temporal thickness (6 regions) and larger subcortical volume (5 regions; all q < .001), but associations were nonlinear (17 of 19 regions). Youth with obesity had lower thickness than healthy weight youth in 8 frontal and temporal regions (largest, −0.21 SD; q < .001), with dorsal frontal differences decreasing across adolescence; underweight youth had smaller subcortical volumes. Higher BMI-for-age z was associated with larger subcortical volume (all 7 regions) within the healthy weight category and lower cortical thickness (11 of 12 regions; fusiform: β = −0.27; q < .001) within the obesity category, steeper than in healthy weight youth in 10 regions, but not in overweight or underweight youth. Within-person associations did not reproduce the obesity associations, reversed from negative at age 10 to positive at age 16, and were more negative in female than male participants.
Conclusions and Relevance
Youth with obesity had lower cortical thickness than healthy weight peers, but associations between brain structure and BMI-for-age differed between CDC weight status groups, suggesting a complex relationship between adiposity and brain structure.
Key Points
Question
How is BMI-for-age associated with brain structure across the weight spectrum, within CDC weight status categories, and within individuals over time in youth?
Findings
In this cohort study of 11,510 youth aged 8–18 years, those with obesity had lower frontal and temporal cortical thickness than healthy weight youth. Within categories, higher BMI-for-age was associated with lower thickness in obesity but larger subcortical volumes in healthy weight youth; within individuals over time, the obesity association was not reproduced.
Meaning
BMI–brain associations differ between CDC weight status categories and may be obscured by assuming a single linear association.
