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Obesity impairs cognitive function via metabolic syndrome and cerebrovascular disease: an SEM analysis in 15,000 adults from the UK Biobank

View ORCID ProfileFilip Morys, Mahsa Dadar, Alain Dagher
doi: https://doi.org/10.1101/2020.06.26.174086
Filip Morys
1Montreal Neurological Institute, McGill University, Montréal, Canada
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  • For correspondence: filip.morys@mail.mcgill.ca
Mahsa Dadar
1Montreal Neurological Institute, McGill University, Montréal, Canada
2Department of Radiology and Nuclear Medicine, Faculty of Medicine, Laval University, Québec, Canada
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Alain Dagher
1Montreal Neurological Institute, McGill University, Montréal, Canada
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Abstract

Chronic obesity is associated with several complications, including cognitive impairment and dementia. However, we have piecemeal knowledge of the mechanisms linking obesity to central nervous system damage. Adiposity leads to the metabolic syndrome, consisting of inflammation, hypertension, dyslipidemia and insulin resistance. In turn, these metabolic abnormalities cause cerebrovascular dysfunction, which may cause white and grey matter tissue loss and consequent cognitive impairment. While there have been several neuroimaging studies linking adiposity to changes in brain morphometry, a comprehensive investigation of the relationship has so far not been done. Here we use structural equation modelling applied to over 15,000 individuals from the UK Biobank to identify the causal chain that links adiposity to cognitive dysfunction. We found that body mass index and waist-to-hip ratio were positively related to higher plasma C-reactive protein, dyslipidemia, occurrence of hypertension and diabetes, all of which were in turn related to cerebrovascular disease as measured by volume of white matter hyperintensities on magnetic resonance imaging. White mater hyperintensities were associated with lower cortical thickness and volume and higher subcortical volumes, which were associated with cognitive deficits on tests of visuospatial memory, fluid intelligence, and working memory among others. In follow-up analyses we found that inflammation, hypertension and diabetes mediated 20% of the relationship between obesity and cerebrovascular disease and that cerebrovascular disease mediated a significant proportion of the relationship between obesity and cortical thickness and volume. We also showed that volume of white matter hyperintensities was related to decreased fractional anisotropy and increased mean diffusivity in the majority of white matter tracts, pointing to white matter dysconnectivity as a major cause of impaired cognition. Our results have clinical implications, supporting a role for the management of adiposity in the prevention of late-life dementia and cognitive decline.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Funding This work was supported by a Foundation Scheme award to AD from the Canadian Institutes of Health Research.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted June 28, 2020.
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Obesity impairs cognitive function via metabolic syndrome and cerebrovascular disease: an SEM analysis in 15,000 adults from the UK Biobank
Filip Morys, Mahsa Dadar, Alain Dagher
bioRxiv 2020.06.26.174086; doi: https://doi.org/10.1101/2020.06.26.174086
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Obesity impairs cognitive function via metabolic syndrome and cerebrovascular disease: an SEM analysis in 15,000 adults from the UK Biobank
Filip Morys, Mahsa Dadar, Alain Dagher
bioRxiv 2020.06.26.174086; doi: https://doi.org/10.1101/2020.06.26.174086

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