Published studies have long found a correlation between obesity in children and decreased executive function.
New research published in JAMA Pediatrics, based on data mined from a massive national research study, suggests that a change in brain structure – a thinner prefrontal cortex – may help explain that interrelationship.
“Our results show an important connection; that kids with higher BMI tend to have a thinner cerebral cortex, especially in the prefrontal area,” said Jennifer Laurent, an associate professor in the Department of Nursing at the University of Vermont and lead author of the study.
The findings are based on data retrieved from a National Institutes of Health-funded research project, the Adolescent Brain Cognitive Development study, or ABCD, which is following 10,000 teens over a 10 year period.
Every two years, study subjects are interviewed, take a battery of tests, give blood samples and undergo brain scans.
The study analyzed results from 3,190 nine- and 10-year-olds recruited at 21 ABCD sites in 2017.
The robust study confirmed the findings of its predecessors; that subjects with higher BMI tended to have lower working memory, as measured by a list sorting test.
But it added an important component to that insight—a physiological correlate in the brain that might help explain the connection.
“Our hypothesis going into the study was that the thickness of the cerebral cortex would ‘mediate’ – or serve as an explanatory link for – the relationship between BMI and executive function,” Laurent said.
The findings did confirm the relationship, according to the study’s senior author, Scott Mackey, an assistant professor of Psychiatry in the University of Vermont’s Larner College of Medicine.
“We found widespread thinning of cerebral cortex” among research subjects with higher BMI, Mackey said, but especially so in the prefontal area.
“That’s significant because we know that executive function, things like memory and the ability to plan, are controlled in that area of the brain,” he said.
More research is needed to determine the nature of the link between the three variables.
“It could be that a thinner prefrontal cortex is affecting decision-making in some children, and they make unhealthy dietary choices as a result, which could lead to obesity,” Laurent said.
Or the causal relationship could work in the opposite direction.
“We know from rodent models and adult studies that obesity can induce low grade inflammatory effects, which actually do alter cellular structure” and can lead to cardiovascular disease, Laurent said.
“With prolonged exposure to obesity, it is possible that children have chronic inflammation, and that may actually be affecting their brain in the long term,” she said.
If that were the case, there would be significant public health implications, Laurent said. “We would want to proactively encourage changes in kids’ diets and exercise levels at a young age with the understanding that it’s not only the heart that is being affected by obesity, it is perhaps also the brain.”
The decrease in working memory was a statistical observation, Laurent said, not a clinical one.
“We did not look at behavior. It’s very important that this work not further stigmatize people who are obese or overweight,” she said.
“What we’re saying is that, according to our measures, we are seeing something that bears watching. How and if it translates to behavior is for future research to determine.”
Data analysis for the study was done at the University of Vermont and Yale University. Richard Watts, director at the FAS Brain Imaging Center and research associate professor of radiology at Yale, was a co-author of the study.
Childhood obesity is an important public-health issue.1 The global prevalence of childhood overweight and obesity has increased substantially since the 1990s, and approximately 60 million children are expected to be obese in 2020.2
In the United States, approximately 17% of children and adolescents were obese and another 15% were overweight during 2009–2010.3 Young children with excess adiposity are more susceptible to becoming overweight or obese in later childhood,4 and at increased risk for adverse health consequences and obesity in adulthood.5
Obesity is associated with lower cognition in adults; these associations may be mediated by pro-inflammatory cytokines, leptin, and C-reactive protein.6,7 In addition, obesity-induced dysregulation of appetite hormones, such as ghrelin and glucagon-like peptide 1 (GLP-1), may have detrimental effects on cognition since these hormones act in multiple brain regions that are relevant to cognitive abilities.7–10 In rodents, both obesity and high fat diets can adversely affect hippocampal-dependent learning.11,12
The association between obesity and cognition in children is less well understood. Previous studies examining childhood weight status and cognition using cross-sectional designs were not able to specify the directionality of this relationship.13,14 Results from prospective studies are inconsistent, possibly due to discrepancies in age and weight distribution, assessment of weight status or cognitive abilities, and confounder adjustment.15–21
Furthermore, only two studies have examined the impact of early-life obesity on childhood cognition, however, both studies focused on early growth. Given that cognition develops rapidly in the first few years of life, it is important to investigate whether weight status in early life has an impact on cognitive function in children during this critical period of neurodevelopment.22
To address these gaps in the current literature, we investigated whether weight status in the first two years of life was associated with an array of cognitive abilities in school-age children using data from a prospective cohort study. Our analysis was guided by the hypothesis that adipose tissue produces adipocytokines or inflammatory molecules that may adversely affect children’s neurodevelopment.
Discussion
In the present study, we investigated the associations between early-life weight status and children’s cognitive abilities in a longitudinal cohort of children from Cincinnati, Ohio. Our findings suggest that early-life WHZ may be inversely associated with FSIQ, PRI, and WMI scores after adjusting for potential confounders. Early-life WHZ was also suggestively associated with higher RT T-scores on the K-CPT/CPT-II. Other measures of cognitive abilities were not associated with early-life WHZ.
Prospective studies examining the association between weight status and cognitive abilities in children have yielded inconsistent results.15–21 Two studies have examined the impact of early-life weight status on cognitive abilities; however, both studies focused on change in BMI or weight over the first few years of life.15,16
In a study of Finnish children, both small and large body size were associated with decreased visual-motor integration at age 56 months.15 This inverted U-shape relationship is similar to the pattern we observed when examining WHZ and children’s PSI, a measure of visual perception and organization, as well as motor skills. In a large population-based study of British children, rapid weight gain between birth and age 25 months (defined as an increase of >0.67 in the SD score of weight) was not associated with cognitive abilities at ages 49 months or 8 years, measured using the WPPSI and WISC-III, respectively.16 Unlike our study, this British study focused on weight gain in the first two years of life, without accounting for children’s height and obesity status.
This could result in misclassification of early life adiposity because children with constant overweight/obesity during the first two years may not be considered as having rapid growth, in contrast, lean children who grew, but did not become overweight or obese were still classified as having rapid growth.
Other prospective studies have examined the impact of obesity in childhood on global measures of cognition, with varied results.17–21 Consistent with one of our findings, two studies reported that obesity at ages 3–5 years was associated with lower cognitive abilities in boys only at ages 5 or 8–12 years.17,18
In contrast, two studies reported that children who were underweight had lower cognitive abilities.19,20 Very few children were underweight in our study, and thus we were not able to precisely examine this association. Finally, a study of Dutch children did not observe associations between BMI at age 4 years and cognitive abilities at age 7 years assessed using the Kaufman Assessment Battery for Children.21
However, this study had a small number of children with overweight (N=18), limiting their statistical power. In sum, discrepancies in the findings above may be explained by differences in the age of exposure and outcome measurements, measures of weight status, weight status distribution of the study population, different lengths of follow-up, measures of cognitive abilities, and adjustment for confounding factors,.15–21
Executive function is a set of self-regulatory cognitive processes that aid in managing thoughts, emotions, and goal-directed behaviors. It includes domains like inhibitory control, working memory, reward sensitivity, and attention.14
Executive function is associated with academic success in children and is critical for physical health and success throughout life.35 Previous studies reported a consistent inverse association between obesity and executive function in children; however, most studies were cross-sectional in design and thus, the directionality of the association cannot be determined.14
Some speculate that children with lower executive function have lower self-regulation of caloric intake and physical activity, which ultimately leads to overweight or obesity, whereas others argue that obesity may decrease executive function through the action of adipocytokines or inflammatory molecules.7,14,36 Moreover, some have proposed a bidirectional relation where low executive function promotes excess adiposity and excess adiposity exacerbates executive function decrements.36
Our results suggest that non-lean children had higher RT T-scores (indicating lower speed of processing and responding) compared to lean children. Some cross-sectional studies included in a systematic review by Reinert et al. reported shorter reaction time and more commission errors among children with higher BMI.14
While the reasons for the inconsistency with our own results is unclear, it is possible that the shorter reaction time in those studies may reflect high impulsivity, which may have led to over-consumption of food and higher BMI. Given the cross-sectional nature of prior studies, it is not possible to delineate the temporal relation between BMI and these executive functions.
In contrast, the longitudinal design of our study ensured that we could determine the directionality of the relationship (from adiposity to executive function) and ensure that it was not influenced by bidirectionality, since weight status was measured years prior to executive function assessment and at an age when eating behavior was more affected by parental influence than children’s self-regulation.37 A population-based study in Germany investigated the 1-year longitudinal associations and found that BMI was not associated with executive function.38
However, the 1-year follow-up time might be too short to allow overweight-associated pathophysiological processes to affect executive function, and they did not adjust for mothers’ BMI in the analysis. The CPT tests utilized in our study assess only the attention and inhibitory control aspects of executive functioning, therefore, additional longitudinal studies with repeated and comprehensive measures of executive function are needed.
In our study, weight status in general was not associated with visual-spatial abilities measured by VMWM, except that weight-for-height may be inversely associated with distance in the VMWM hidden platform trials among boys (Table S3–S4).
We found that early-life WHZ was inversely associated with performance on Block Design test, a PRI subtest that also measures visuospatial organization. Consistent with our findings, BMI was inversely associated with block design test performance among school-age US children and adolescents in a cross-sectional study.13 Some other studies examined the relationship between obesity and visual-spatial abilities in children. In a UK cohort study, obesity at age 3 was associated with worse visuospatial skills at age 5 in boys.18
A randomized controlled trial conducted among school-age Danish children found that visuospatial construction skills were improved after obesity intervention among children with overweight or obesity, indicating that obesity may play a detrimental role in visual-spatial abilities.39
The underlying mechanisms for these sex-specific effects are unclear. Sex hormones or psychosocial factors may partly explain the differences. Given the sparsity of the current literature, additional prospective studies are needed to confirm these findings and examine whether the associations differ by sex.
There are several biological mechanisms by which early life adiposity could affect neurodevelopment. Adipose tissue produces pro-inflammatory cytokines that activate inflammatory pathways in children and adults.7 Systematic inflammation may affect multiple brain regions relevant to cognitive abilities, and was shown to adversely affect spatial learning and memory in rodents.7
In addition, the dysregulation of appetite-regulating hormones among children with excess adiposity may adversely affect cognition.7 Ghrelin, a hunger hormone, can cross the blood-brain-barrier and activate hippocampal regions to improve memory in rodents.9 GLP-1, which promotes satiety, also acts on multiple brain regions that are involved in cognitive abilities, such as the hypothalamus and the prefrontal cortex.8 In rodents deficiencies in ghrelin and GLP-1 caused deficits in learning and memory.7,10
Our study had some limitations. This study had limited statistical power to detect small effects and precisely estimate associations, especially for children who were overweight/obese, because of our modest sample size.
Thus, we were not able to examine children with obesity and overweight separately. However, by using different categories of weight status, we were able to examine the group of children who were at the high-end of normal WHZ range (>1SD) compared to lean children (≤1SD), which brings attention to this group of children who are at risk of being overweight or obese later in childhood and adolescence.40 Furthermore, while WHZ at age 2 years was used in most children as an exposure, WHZ at age 1 year was used in some children when 2-year data were not available. However, 2-year WHZ was highly correlated with 1-year, 3-year, and 4-year WHZ in this study, which reduced the possibility of exposure misclassification.
The correlation pattern (and the one observed for repeated BMI z-scores, Table S7) indicates that 2-year WHZ tends to predict weight status in childhood, which is consistent with previous findings.4 Another limitation is that we did not use direct measurement of adiposity, such as dual energy X-ray absorptiometry, which can provide a more accurate assessment of body composition.41
However, given that young children may not be cooperative for this measurement, WHZ is a more practical measurement of excess weight in early childhood and is endorsed by WHO to assess body composition for children under 5 years. Finally, we made several comparisons and it is possible that some of our results may be chance findings. However, adjusting for multiple comparisons may undeservedly reduce statistical power42, and the general pattern of our results suggests an inverse association between early life adiposity and cognitive abilities.
Our study had several strengths. Our prospective data enabled us to investigate whether weight status in the critical period of brain development – the first two years of life – impacts cognitive abilities in childhood.
Compared to prior cross-sectional studies examining the association between childhood weight status and cognition, the prospective design helped us determine the directionality of the association. Furthermore, we repeatedly administered valid and reliable neuropsychological tests to assess an array of cognitive abilities.
In addition, weight and length/height were measured by trained study staff, rather than self-reported by parents, which provided more accurate measurements and reduced potential exposure misclassification. Finally, we collected detailed information on covariates in this study, which enabled us to adjust for multiple potential confounding factors including sociodemographic factors, perinatal factors, and maternal IQ.
Conclusion
Excess early-life weight-for-height may be inversely associated with full-scale IQ, perceptual reasoning scores, and working memory scores (boys only), and suggestively associated with longer reaction time among school-aged children. Future prospective cohort studies should confirm these findings and investigate if early-life weight-for-height is associated with school performance, attention-deficit/hyperactivity disorder diagnosis, learning disabilities, or special education service use.
More information: Jennifer S. Laurent et al, Associations Among Body Mass Index, Cortical Thickness, and Executive Function in Children, JAMA Pediatrics (2019). DOI: 10.1001/jamapediatrics.2019.4708
