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Clinical Research

Evidence of association between obesity and lower cerebral myelin content in cognitively unimpaired adults

International Journal of Obesity volume 45, pages 850–859 (2021)Cite this article

Subjects

Abstract

Background

Myelin loss is a central feature of several neurodegenerative diseases, including Alzheimer’s disease (AD). In animal studies, a link has been established between obesity and impairment of oligodendrocyte maturation, the cells that produce and maintain myelin. Although clinical magnetic resonance imaging (MRI) studies have revealed microstructural alterations of cerebral white matter tissue in subjects with obesity, no specific myelin vs. obesity correlation studies have been performed in humans using a direct myelin content metric.

Objectives

To assess the association between obesity and myelin integrity in cerebral white matter using advanced MRI methodology for myelin content imaging.

Methods

Studies were performed in the clinical unit of the National Institute on Aging on a cohort of 119 cognitively unimpaired adults. Using advanced MRI methodology, we measured whole-brain myelin water fraction (MWF), a marker of myelin content. Automated brain mapping algorithms and statistical models were used to evaluate the relationships between MWF and obesity, measured using the body mass index (BMI) or waist circumference (WC), in various white matter brain regions.

Results

MWF was negatively associated with BMI or WC in all brain regions evaluated. These associations, adjusted for sex, ethnicity, and age, were statistically significant in most brain regions examined (p < 0.05), with higher BMI or WC corresponding to lower myelin content. Finally, in agreement with previous work, MWF exhibited a quadratic, inverted U-shaped, association with age; this is attributed to the process of myelination from youth through middle age, followed by demyelination afterward.

Conclusions

These findings suggest that obesity was significantly associated with white matter integrity, and in particular myelin content. We expect that this work will lay the foundation for further investigations to clarify the nature of myelin damage in neurodegeneration, including AD, and the effect of lifestyle factors such as diet and physical activity on myelination.

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Fig. 1: Visualization of the white matter ROIs investigated.
Fig. 2: Regression results for the relationship between MWF and BMI adjusted for age, age2, sex, and ethnicity (N = 119).
Fig. 3: Regression results for the relationship between MWF and WC adjusted for age, age2, sex, and ethnicity (N = 119).

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References

  1. Mazon JN, de Mello AH, Ferreira GK, Rezin GT. The impact of obesity on neurodegenerative diseases. Life Sci. 2017;182:22–8.

    Article  CAS  PubMed  Google Scholar 

  2. Stillman CM, Weinstein AM, Marsland AL, Gianaros PJ, Erickson KI. Body-brain connections: the effects of obesity and behavioral interventions on neurocognitive aging. Front Aging Neurosci. 2017;9:115.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Jagust W, Harvey D, Mungas D, Haan M. Central obesity and the aging brain. Arch Neurol. 2005;62:1545–8.

    Article  PubMed  Google Scholar 

  4. Uranga RM, Keller JN. The complex interactions between obesity, metabolism and the brain. Front Neurosc. 2019;13:513.

    Article  Google Scholar 

  5. Bhat ZF, Morton JD, Mason S, Bekhit AEA, Bhat HF. Obesity and neurological disorders: dietary perspective of a global menace. Crit Rev Food Sci Nutr. 2019;59:1294–310.

    Article  PubMed  Google Scholar 

  6. Alford S, Patel D, Perakakis N, Mantzoros CS. Obesity as a risk factor for Alzheimer’s disease: weighing the evidence. Obes Rev. 2018;19:269–80.

    Article  CAS  PubMed  Google Scholar 

  7. Chen H, Zhang SM, Schwarzschild MA, Hernan MA, Willett WC, Ascherio A. Obesity and the risk of Parkinson’s disease. Am J Epidemiol. 2004;159:547–55.

    Article  PubMed  Google Scholar 

  8. Ashrafian H, Harling L, Darzi A, Athanasiou T. Neurodegenerative disease and obesity: what is the role of weight loss and bariatric interventions? Metab Brain Dis. 2013;28:341–53.

    Article  PubMed  Google Scholar 

  9. Graham LC, Grabowska WA, Chun Y, Risacher SL, Philip VM, Saykin AJ, et al. Exercise prevents obesity-induced cognitive decline and white matter damage in mice. Neurobiol Aging. 2019;80:154–72.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Erickson KI, Weinstein AM, Lopez OL. Physical activity, brain plasticity, and Alzheimer’s disease. Arch Med Res. 2012;43:615–21.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kullmann S, Callaghan MF, Heni M, Weiskopf N, Scheffler K, Häring H-U, et al. Specific white matter tissue microstructure changes associated with obesity. NeuroImage. 2016;125:36–44.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Mueller K, Anwander A, Möller HE, Horstmann A, Lepsien J, Busse F, et al. Sex-dependent influences of obesity on cerebral white matter investigated by diffusion-tensor imaging. PLoS ONE. 2011;6:e18544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Schall M, Iordanishvili E, Mauler J, Oros-Peusquens AM, Shah NJ. Increasing body mass index in an elderly cohort: effects on the quantitative MR parameters of the brain. J Magn Reson Imaging. 2020;51:514–23.

    Article  PubMed  Google Scholar 

  14. Birdsill AC, Oleson S, Kaur S, Pasha E, Ireton A, Tanaka H, et al. Abdominal obesity and white matter microstructure in midlife. Hum Brain Mapp. 2017;38:3337–44.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Xu J, Li Y, Lin H, Sinha R, Potenza MN. Body mass index correlates negatively with white matter integrity in the fornix and corpus callosum: a diffusion tensor imaging study. Human Brain Mapp. 2013;34:1044–52.

    Article  Google Scholar 

  16. Raji CA, Ho AJ, Parikshak NN, Becker JT, Lopez OL, Kuller LH, et al. Brain structure and obesity. Human Brain Mapp. 2010;31:353–64.

    Google Scholar 

  17. Gazdzinski S, Kornak J, Weiner MW, Meyerhoff DJ. Body mass index and magnetic resonance markers of brain integrity in adults. Ann Neurol. 2008;63:652–7.

    Article  PubMed  PubMed Central  Google Scholar 

  18. MacKay AL, Laule C. Magnetic resonance of myelin water: an in vivo marker for myelin. Brain Plast. 2016;2:71–91.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Bouhrara M, Spencer RG. Incorporation of nonzero echo times in the SPGR and bSSFP signal models used in mcDESPOT. Magn Reson Med. 2015;74:1227–35.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Bouhrara M, Spencer RG. Improved determination of the myelin water fraction in human brain using magnetic resonance imaging through Bayesian analysis of mcDESPOT. NeuroImage. 2016;127:456–71.

    Article  PubMed  Google Scholar 

  21. Bouhrara M, Spencer RG. Rapid simultaneous high-resolution mapping of myelin water fraction and relaxation times in human brain using BMC-mcDESPOT. NeuroImage. 2017;147:800–11.

    Article  CAS  PubMed  Google Scholar 

  22. Bouhrara M, Reiter DA, Celik H, Fishbein KW, Kijowski R, Spencer RG. Analysis of mcDESPOT- and CPMG-derived parameter estimates for two-component nonexchanging systems. Magn Reson Med. 2016;75:2406–20.

    Article  CAS  PubMed  Google Scholar 

  23. Bouhrara M, Reiter D, Bergeron C, Zukley L, Ferrucci L, Resnick S, et al. Evidence of demyelination in mild cognitive impairment and dementia using a direct and specific magnetic resonance imaging measure of myelin content. Alzheimers Dement. 2018;14:998–1004.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Bouhrara M, Cortina LE, Rejimon AC, Khattar N, Bergeron C, Bergeron J, et al. Quantitative age-dependent differences in human brainstem myelination assessed using high-resolution magnetic resonance mapping. NeuroImage. 2020;206:116307.

    Article  PubMed  Google Scholar 

  25. Bouhrara M, Rejimon AC, Cortina LE, Khattar N, Bergeron CM, Ferrucci L, et al. Adult brain aging investigated using BMC-mcDESPOT based myelin water fraction imaging. Neurobiol Aging. 2020;85:131–9.

    Article  PubMed  Google Scholar 

  26. Qian W, Khattar N, Cortina LE, Spencer RG, Bouhrara M. Nonlinear associations of neurite density and myelin content with age revealed using multicomponent diffusion and relaxometry magnetic resonance imaging. NeuroImage. 2020;223:117369.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bouhrara M, Alisch J, Nikkita N, Kim R, Rejimon A, Cortina L, et al. Association of cerebral blood flow with myelin content in cognitively unimpaired adults. BMJ Neurol Open. 2020;2:e000053.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Dean DC III, Sojkova J, Hurley S, Kecskemeti S, Okonkwo O, Bendlin BB, et al. Alterations of myelin content in parkinson’s disease: a cross-sectional neuroimaging study. PLoS ONE. 2016;11:e0163774.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Bartzokis G. Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer’s disease. Neurobiol Aging. 2004;25:5–18.

    Article  CAS  PubMed  Google Scholar 

  30. Bartzokis G. Alzheimer’s disease as homeostatic responses to age-related myelin breakdown. Neurobiol Aging. 2011;32:1341–71.

    Article  CAS  PubMed  Google Scholar 

  31. Huang H-T, Tsai S-F, Wu H-T, Huang H-Y, Hsieh H-H, Kuo Y-M, et al. Chronic exposure to high fat diet triggers myelin disruption and interleukin-33 upregulation in hypothalamus. BMC Neurosci. 2019;20:33.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Xiao G, Burguet J, Kawaguchi R, Havton LA, Hinman JD. Obesity restricts oligodendrocyte maturation and impedes repair after white matter stroke. bioRxiv. 2018:283184. https://www.biorxiv.org/content/10.1101/283184v2.

  33. Janssen I, Katzmarzyk PT, Ross R. Body mass index, waist circumference, and health risk: evidence in support of current National Institutes of Health guidelines. Arch Intern Med. 2002;162:2074–9.

    Article  PubMed  Google Scholar 

  34. Deoni SC. Correction of main and transmit magnetic field (B0 and B1) inhomogeneity effects in multicomponent-driven equilibrium single-pulse observation of T1 and T2. Magn Reson Med. 2011;65:1021–35.

    Article  PubMed  Google Scholar 

  35. Jenkinson M, Beckmann CF, Behrens TE, Woolrich MW, Smith SM. FSL. NeuroImage. 2012;62:782–90.

    Article  PubMed  Google Scholar 

  36. Arshad M, Stanley JA, Raz N. Adult age differences in subcortical myelin content are consistent with protracted myelination and unrelated to diffusion tensor imaging indices. NeuroImage. 2016;143:26–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Paternoster R, Brame R, Mazerolle P, Piquero A. Using the correct statistical test for the equality of regression coefficients. Criminology. 1998;36:859–66.

    Article  Google Scholar 

  38. Rocca MA, Preziosa P, Mesaros S, Pagani E, Dackovic J, Stosic-Opincal T, et al. Clinically isolated syndrome suggestive of multiple sclerosis: dynamic patterns of gray and white matter changes-A 2-year MR imaging study. Radiology. 2016;278:841–53.

    Article  PubMed  Google Scholar 

  39. Sabin ND, Cheung YT, Reddick WE, Bhojwani D, Liu W, Glass JO, et al. The impact of persistent leukoencephalopathy on brain white matter microstructure in long-term survivors of acute lymphoblastic leukemia treated with chemotherapy only. Am J Neuroradiol. 2018;39:1919–25.

    Article  CAS  PubMed  Google Scholar 

  40. Karababa IF, Bayazıt H, Kılıçaslan N, Celik M, Cece H, Karakas E, et al. Microstructural changes of anterior corona radiata in bipolar depression. Psychiatry Investig. 2015;12:367–71.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Sanjuan PM, Thoma R, Claus ED, Mays N, Caprihan A. Reduced white matter integrity in the cingulum and anterior corona radiata in posttraumatic stress disorder in male combat veterans: a diffusion tensor imaging study. Psychiatry Res. 2013;214:260–8.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Raji CA, Ho AJ, Parikshak NN, Becker JT, Lopez OL, Kuller LH, et al. Brain structure and obesity. Hum Brain Mapp. 2010;31:353–64.

    PubMed  Google Scholar 

  43. Kullmann S, Schweizer F, Veit R, Fritsche A, Preissl H. Compromised white matter integrity in obesity. Obes Rev. 2015;16:273–81.

    Article  CAS  PubMed  Google Scholar 

  44. Spangaro M, Mazza E, Poletti S, Cavallaro R, Benedetti F. Obesity influences white matter integrity in schizophrenia. Psychoneuroendocrinology. 2018;97:135–42.

    Article  PubMed  Google Scholar 

  45. Alarcon G, Ray S, Nagel BJ. Lower working memory performance in overweight and obese adolescents is mediated by white matter microstructure. J Int Neuropsychol Soc. 2016;22:281–92.

    Article  PubMed  Google Scholar 

  46. Olivo G, Latini F, Wiemerslage L, Larsson E-M, Schiöth HB. Disruption of accumbens and thalamic white matter connectivity revealed by diffusion tensor tractography in young men with genetic risk for obesity. Front Hum Neurosci. 2018;12:75.

  47. Stricker NH, Schweinsburg BC, Delano-Wood L, Wierenga CE, Bangen KJ, Haaland KY, et al. Decreased white matter integrity in late-myelinating fiber pathways in Alzheimer’s disease supports retrogenesis. NeuroImage. 2009;45:10–6.

    Article  CAS  PubMed  Google Scholar 

  48. Brickman AM, Meier IB, Korgaonkar MS, Provenzano FA, Grieve SM, Siedlecki KL, et al. Testing the white matter retrogenesis hypothesis of cognitive aging. Neurobiol Aging. 2012;33:1699–715.

    Article  PubMed  Google Scholar 

  49. Raz N. Aging of the brain and its impact on cognitive performance: integration of structural and functional findings. The handbook of aging and cognition. 2nd ed. Mahwah, NJ: Lawrence Erlbaum Associates Publishers; 2000. p. 1–90.

    Google Scholar 

  50. Bender AR, Völkle MC, Raz N. Differential aging of cerebral white matter in middle-aged and older adults: a seven-year follow-up. NeuroImage. 2016;125:74–83.

    Article  PubMed  Google Scholar 

  51. Repple J, Opel N, Meinert S, Redlich R, Hahn T, Winter NR, et al. Elevated body-mass index is associated with reduced white matter integrity in two large independent cohorts. Psychoneuroendocrinology. 2018;91:179–85.

    Article  Google Scholar 

  52. Karlsson HK, Tuulari JJ, Hirvonen J, Lepomaki V, Parkkola R, Hiltunen J, et al. Obesity is associated with white matter atrophy: a combined diffusion tensor imaging and voxel-based morphometric study. Obesity. 2013;21:2530–7.

    Article  PubMed  Google Scholar 

  53. Dekkers IA, Jansen PR, Lamb HJ. Obesity, brain volume, and white matter microstructure at MRI: a cross-sectional UK Biobank Study. Radiology. 2019;291:763–71.

    Article  PubMed  Google Scholar 

  54. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. 2013;309:71–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Winter JE, MacInnis RJ, Wattanapenpaiboon N, Nowson CA. BMI and all-cause mortality in older adults: a meta-analysis. Am J Clin Nutr. 2014;99:875–90.

    Article  CAS  PubMed  Google Scholar 

  56. Staiano AE, Reeder BA, Elliott S, Joffres MR, Pahwa P, Kirkland SA, et al. Body mass index versus waist circumference as predictors of mortality in Canadian adults. Int J Obes. 2012;36:1450–4.

    Article  CAS  Google Scholar 

  57. Janssen I, Katzmarzyk PT, Ross R. Waist circumference and not body mass index explains obesity-related health risk. Am J Clin Nutr. 2004;79:379–84.

    Article  CAS  PubMed  Google Scholar 

  58. Kuk JL, Katzmarzyk PT, Nichaman MZ, Church TS, Blair SN, Ross R. Visceral fat is an independent predictor of all-cause mortality in men. Obesity. 2006;14:336–41.

    Article  PubMed  Google Scholar 

  59. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004;4:579–91.

    Article  CAS  PubMed  Google Scholar 

  60. Bartzokis G, Lu PH, Tingus K, Mendez MF, Richard A, Peters DG, et al. Lifespan trajectory of myelin integrity and maximum motor speed. Neurobiol Aging. 2010;31:1554–62.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the Intramural Research Program of the National Institute on Aging of the National Institutes of Health. We gratefully acknowledge Christopher M. Bergeron, Denise Melvin, and Linda Zukley for their assistance with data acquisition, participant recruitment, and logistics.

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Author notes

  1. These authors contributed equally: Mustapha Bouhrara, Nikkita Khattar

Authors and Affiliations

  1. Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA

    Mustapha Bouhrara, Nikkita Khattar & Richard G. Spencer

  2. Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA

    Palchamy Elango & Luigi Ferrucci

  3. Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA

    Susan M. Resnick

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Correspondence to Mustapha Bouhrara.

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Bouhrara, M., Khattar, N., Elango, P. et al. Evidence of association between obesity and lower cerebral myelin content in cognitively unimpaired adults. Int J Obes 45, 850–859 (2021). https://doi.org/10.1038/s41366-021-00749-x

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