Preliminary evidence of cognitive and brain abnormalities in uncomplicated adolescent obesity

Po Lai Yau, Esther H Kang, David C Javier, Antonio Convit, Po Lai Yau, Esther H Kang, David C Javier, Antonio Convit

Abstract

Objective: To ascertain whether pediatric obesity without clinically significant insulin resistance (IR) impacts brain structure and function.

Methods: Thirty obese and 30 matched lean adolescents, all without clinically significant IR or a diagnosis of metabolic syndrome (MetS), received comprehensive endocrine, neuropsychological, and MRI evaluations.

Results: Relative to lean adolescents, obese non-IR adolescents had significantly lower academic achievement (i.e., arithmetic and spelling) and tended to score lower on working memory, attention, psychomotor efficiency, and mental flexibility. In line with our prior work on adolescent MetS, memory was unaffected in uncomplicated obesity. Reductions in the thickness of the orbitofrontal and anterior cingulate cortices as well as reductions of microstructural integrity in major white matter tracts without gross volume changes were also uncovered.

Conclusions: It was documented, for the first time, that adolescents with uncomplicated obesity already have subtle brain alterations and lower performance in selective cognitive domains. When interpreting these preliminary data in the context of our prior reports of similar, but more extensive brain findings in obese adolescents with MetS and T2DM, it was concluded that "uncomplicated" obesity may also result in subtle brain alterations, suggesting a possible dose effect with more severe metabolic dysregulation giving rise to greater abnormalities.

Conflict of interest statement

Conflict of Interest: The authors have indicated they have no potential conflicts of interest to disclose.

Copyright © 2014 The Obesity Society.

Figures

Figure 1
Figure 1
Six of the seven clusters demonstrating significant FA group differences are displayed in order of cluster size (VANCOVA analysis controlling for age; minimum cluster size of 100 voxels; P<0.005; clusters in blue represent FA reductions in obese adolescents whereas positive associations in yellow represent FA elevation). Each column shows three orthogonal orientations of the average normalized structural image illustrating a significant cluster with the axes passing through the centroid of the cluster. The largest cluster, found in the left temporal stem, was the only one that remained significant at a more conservative P-vlaue threshold of 0.001.

References

    1. James PT. Obesity: the worldwide epidemic. Clin Dermatol. 2004;22:276–280.
    1. Wang Y, Beydoun MA. The obesity epidemic in the United States--gender, age, socioeconomic, racial/ethnic, and geographic characteristics: a systematic review and meta-regression analysis. Epidemiol Rev. 2007;29:6–28.
    1. Constantino MI, Molyneaux L, Limacher-Gisler F, Al-Saeed A, Luo C, Wu T, et al. Long-term complications and mortality in young-onset diabetes: type 2 diabetes is more hazardous and lethal than type 1 diabetes. Diabetes Care. 2013;36:3863–3869.
    1. Pannacciulli N, Del Parigi A, Chen K, Le DS, Reiman EM, Tataranni PA. Brain abnormalities in human obesity: a voxel-based morphometric study. Neuroimage. 2006;31:1419–1425.
    1. Gunstad J, Paul RH, Cohen RA, Tate DF, Spitznagel MB, Gordon E. Elevated body mass index is associated with executive dysfunction in otherwise healthy adults. Compr Psychiatry. 2007;48:57–61.
    1. Li X. A study of intelligence and personality in children with simple obesity. Int J Obes Relat Metab Disord. 1995;19:355–357.
    1. Falkner NH, Neumark-Sztainer D, Story M, Jeffery RW, Beuhring T, Resnick MD. Social, educational, and psychological correlates of weight status in adolescents. Obes Res. 2001;9:32–42.
    1. Lokken KL, Boeka AG, Austin HM, Gunstad J, Harmon CM. Evidence of executive dysfunction in extremely obese adolescents: a pilot study. Surg Obes Relat Dis. 2009;5:547–552.
    1. Cserjesi R, Luminet O, Poncelet AS, Lenard L. Altered executive function in obesity. Exploration of the role of affective states on cognitive abilities. Appetite. 2009;52:535–539.
    1. Gunstad J, Spitznagel MB, Paul RH, Cohen RA, Kohn M, Luyster FS, et al. Body mass index and neuropsychological function in healthy children and adolescents. Appetite. 2008;50:246–251.
    1. Moreno-Lopez L, Soriano-Mas C, Delgado-Rico E, Rio-Valle JS, Verdejo-Garcia A. Brain structural correlates of reward sensitivity and impulsivity in adolescents with normal and excess weight. PLoS One. 2012;7:e49185.
    1. Thamotharan S, Lange K, Zale EL, Huffhines L, Fields S. The role of impulsivity in pediatric obesity and weight status: a meta-analytic review. Clin Psychol Rev. 2013;33:253–262.
    1. Yau PL, Javier DC, Ryan CM, Tsui WH, Ardekani BA, Ten S, et al. Preliminary evidence for brain complications in obese adolescents with type 2 diabetes mellitus. Diabetologia. 2010;53:2298–2306.
    1. Bruehl H, Sweat V, Tirsi A, Shah B, Convit A. Obese Adolescents with type 2 diabetes mellitus have hippocampal and frontal lobe volume reductions. Neurosci Med. 2011;2:34–42.
    1. Yau PL, Castro MG, Tagani A, Tsui WH, Convit A. Obesity and metabolic syndrome and functional and structural brain impairments in adolescence. Pediatrics. 2012;130:e856–864.
    1. Maayan L, Hoogendoorn C, Sweat V, Convit A. Disinhibited eating in obese adolescents is associated with orbitofrontal volume reductions and executive dysfunction. Obesity (Silver Spring) 2011;19:1382–1387.
    1. Davids S, Lauffer H, Thoms K, Jagdhuhn M, Hirschfeld H, Domin M, et al. Increased dorsolateral prefrontal cortex activation in obese children during observation of food stimuli. Int J Obes. 2010;34:94–104.
    1. Centers for Disease Control and Prevention. BMI for children and teens. 2009 Retrieved August 10, 2009, from .
    1. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004;114(2 suppl 4th report):555–576.
    1. Turchiano M, Sweat V, Fierman A, Convit A. Obesity, metabolic syndrome, and insulin resistance in urban high school students of minority race/ethnicity. Arch Pediatr Adolesc Med. 2012:1–7.
    1. Lezak MD, Howieson DB, Loring DW. Neuropsychological Assessment. Oxford University Press; New York: 2004.
    1. Mindell JA, Owens JA. A clinical guide to pediatric sleep: Diagnosis and management of sleep problems. Lippincott Williams & Wilkins; Philadelphia: 2003.
    1. Macey PM, Kumar R, Woo MA, Valladares EM, Yan-Go FL, Harper RM. Brain structural changes in obstructive sleep apnea. Sleep. 2008;31:967–977.
    1. Gozal D, Kheirandish-Gozal L. Neurocognitive and behavioral morbidity in children with sleep disorders. Curr Opin Pulm Med. 2007;13:505–509.
    1. Beck A, Steer RA, Brown GK. Manual for Beck Depression Inventory-II. Psychological Corporation; San Antonio, TX: 1996.
    1. Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35:1381–1395.
    1. Convit A, de Leon MJ, Tarshish C, De Santi S, Tsui W, Rusinek H, et al. Specific hippocampal volume reductions in individuals at risk for Alzheimer’s disease. Neurobiol Aging. 1997;18:131–138.
    1. Convit A, Wolf OT, de Leon MJ, Patalinjug M, Kandil E, Cardebat D, et al. Volumetric analysis of the pre-frontal regions: findings in aging and schizophrenia. Psychiatry Res. 2001;107:61–73.
    1. Fischl B, Liu A, Dale AM. Automated manifold surgery: constructing geometrically accurate and topologically correct models of the human cerebral cortex. IEEE Trans Med Imaging. 2001;20:70–80.
    1. Fischl B, Sereno MI, Dale AM. Cortical surface-based analysis. II: Inflation, flattening, and a surface-based coordinate system. Neuroimage. 1999;9:195–207.
    1. Fischl B, Salat DH, van der Kouwe A, Makris N, Segonne F, Quinn BT, et al. Sequence-independent segmentation of magnetic resonance images. Neuroimage. 2004;23:S69–84.
    1. Ardekani BA, Guckemus S, Bachman A, Hoptman MJ, Wojtaszek M, Nierenberg J. Quantitative comparison of algorithms for inter-subject registration of 3D volumetric brain MRI scans. J Neurosci Methods. 2005;142:67–76.
    1. Yau PL, Javier D, Tsui W, Sweat V, Bruehl H, Borod JC, et al. Emotional and neutral declarative memory impairments and associated white matter microstructural abnormalities in adults with type 2 diabetes. Psychiatry Res. 2009;174:223–230.
    1. Maayan LHC, Sweat V, Convit A. Disinhibited eating in obese adolescents is associated with orbitofrontal volume reductions and executive dysfunction. Obesity. 2011 In Press.
    1. Widjaja E, Zarei Mahmoodabadi S, Go C, Raybaud C, Chuang S, Snead OC, et al. Reduced cortical thickness in children with new-onset seizures. AJNR Am J Neuroradiol. 2012;33:673–677.
    1. Nummenmaa L, Hirvonen J, Hannukainen JC, Immonen H, Lindroos MM, Salminen P, et al. Dorsal striatum and its limbic connectivity mediate abnormal anticipatory reward processing in obesity. PLoS One. 2012;7:e31089.
    1. Huang K, Zou CC, Yang XZ, Chen XQ, Liang L. Carotid intima-media thickness and serum endothelial marker levels in obese children with metabolic syndrome. Arch Pediatr Adolesc Med. 2010;164:846–851.
    1. Iannuzzi A, Licenziati MR, Acampora C, Renis M, Agrusta M, Romano L, et al. Carotid artery stiffness in obese children with the metabolic syndrome. Am J Cardiol. 2006;97:528–531.
    1. Montero D, Walther G, Perez-Martin A, Roche E, Vinet A. Endothelial dysfunction, inflammation, and oxidative stress in obese children and adolescents: markers and effect of lifestyle intervention. Obes Rev. 2012;13:441–455.
    1. Convit A. Links between cognitive impairment in insulin resistance: An explanatory model. Neurobiol Aging. 2005;26:31–35.

Source: PubMed

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