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Impact of elevated body mass index (BMI) on cognitive functioning and inflammation in persons with post-COVID-19 condition: a secondary analysis

Published online by Cambridge University Press:  12 April 2024

Gia Han Le ,
Angela T.H. Kwan ,
Ziji Guo ,
Sabrina Wong ,
Sebastian Badulescu ,
Hartej Gill ,
Kayla M. Teopiz ,
Shakila Meshkat Open the ORCID record for Shakila Meshkat [Opens in a new window] ,
Felicia Ceban  and
Lee Phan
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Gia Han Le
Affiliation:
Institute of Medical Science, University of Toronto, Toronto, ON, Canada Brain and Cognition Discovery Foundation, Toronto, ON, Canada
Angela T.H. Kwan
Affiliation:
Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada
Ziji Guo
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada
Sabrina Wong
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, ON, Canada Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
Sebastian Badulescu
Affiliation:
Institute of Medical Science, University of Toronto, Toronto, ON, Canada Brain and Cognition Discovery Foundation, Toronto, ON, Canada
Hartej Gill
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, ON, Canada
Kayla M. Teopiz
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, ON, Canada
Shakila Meshkat
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, ON, Canada
Felicia Ceban
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, ON, Canada Michael G. DeGroote School of Medicine. McMaster University, Hamilton, ON, Canada
Lee Phan
Affiliation:
Institute of Medical Science, University of Toronto, Toronto, ON, Canada
Mehala Subramaniapillai
Affiliation:
Institute of Medical Science, University of Toronto, Toronto, ON, Canada
Joshua D. Di Vincenzo
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, ON, Canada
Joshua D. Rosenblat
Affiliation:
Institute of Medical Science, University of Toronto, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
Rodrigo B. Mansur
Affiliation:
Institute of Medical Science, University of Toronto, Toronto, ON, Canada Brain and Cognition Discovery Foundation, Toronto, ON, Canada
Giacomo d’Andrea
Affiliation:
Department of Neuroscience, Imaging and Clinical Sciences University “G d’Annunzio”, Chieti, Italy
Roger Ho
Affiliation:
Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, Singapore
Taeho Greg Rhee
Affiliation:
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA Department of Public Health Sciences, University of Connecticut School of Medicine, Farmington, CT, USA
Roger S. McIntyre*
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
*
Corresponding author: Roger S. McIntyre; Email: roger.mcintyre@bcdf.org
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Abstract

Background:

Individuals who have recovered from the acute stage of SARS-CoV-2 infection may be at risk of developing post-COVID-19 condition (PCC), characterised by a spectrum of persisting, non-specific, and functionally impairing symptoms across multiple organ systems. Obesity has been implicated as a risk factor for PCC, mediated by chronic systemic inflammation. The foregoing has also been separately reported to mediate cognitive dysfunction in PCC.

Methods:

This is a post-hoc analysis of a randomised, double-blinded, placebo-controlled clinical trial evaluating vortioxetine treatment for cognitive impairments in persons with PCC who received vortioxetine or placebo for eight weeks. This analysis comprises baseline data, examining the impact of BMI on cognitive functioning measured by the Digit Symbol Substitution Test (DSST) and Trails Making Tests (TMT)-A/B, as well as inflammation, via serum c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

Results:

Complete data from 70 participants were statistically analysed and adjusted for age and sex. BMI was negatively correlated with performance on the DSST (β = −0.003, p = 0.047), TMT-A (β = −0.006, p = 0.025), and TMT-B (β = −0.006, p = 0.002). BMI was positively correlated with serum CRP (unstandardized β = 0.193, standardized β = 0.612, p < 0.001) and ESR (β = 0.039, p < 0.001) levels.

Conclusion:

We observed a significant negative correlation between BMI and cognitive functioning, and a significant positive correlation between BMI and inflammation in persons with PCC, suggesting a bidirectional interplay between BMI, PCC, and cognitive function; individuals with an elevated BMI may be at a greater risk of developing PCC and/or presenting with greater cognitive deficits mediated by chronic systemic inflammation.

Keywords

Post-COVID conditioncognitioninflammationobesitylong COVID
Type
Original Article
Information
Acta Neuropsychiatrica , First View , pp. 1 - 7
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Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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References

Almeria, M, Cejudo, JC, Sotoca, J, et al. (2020) Cognitive profile following covid-19 infection: clinical predictors leading to neuropsychological impairment. Brain, Behavior, and Immunity – Health 9, 100163. DOI: 10.1016/j.bbih.2020.100163.CrossRefGoogle ScholarPubMed
Bonsaksen, T, Leung, J, Price, D, et al. (2022) Self-reported long COVID in the general population: sociodemographic and health correlates in a cross-national sample. Life 12(6), 901. DOI: 10.3390/life12060901.CrossRefGoogle Scholar
Bora, E, McIntyre, RS and Ozerdem, A (2019) Neurocognitive and neuroimaging correlates of obesity and components of metabolic syndrome in bipolar disorder: a systematic review. Psychological Medicine 49(5), 738–749. DOI: 10.1017/S0033291718003008.CrossRefGoogle ScholarPubMed
Bradley, JR (2008) TNF-mediated inflammatory disease. Journal of Pathology 214(2), 149–160. DOI: 10.1002/path.2287.CrossRefGoogle ScholarPubMed
Ceban, F, Ling, S, Lui, LMW, et al. (2022) Fatigue and cognitive impairment in post-COVID-19 syndrome: a systematic review and meta-analysis. Brain Behavior and Immunity 101, 93–135. DOI: 10.1016/j.bbi.2021.12.020.CrossRefGoogle ScholarPubMed
Centers for Disease Control and Prevention (n.d.) Defining adult overweight & obesity [Internet]. https://www.cdc.gov/obesity/basics/adult-defining.html [cited 2023 April 1].Google Scholar
Cogstate (n.d.) Digital cognitive assessment [Internet]. https://www.cogstate.com/clinical-trials/digital-cognitive-assessment/?cn-reloaded=1 [cited 2023 April 1].Google Scholar
Dalkner, N, Reininghaus, E, Schwalsberger, K, et al. (2020) C-reactive protein as a possible predictor of trail-making performance in individuals with psychiatric disorders. Nutrients 12(10), 3019. DOI: 10.3390/nu12103019.CrossRefGoogle ScholarPubMed
Damiano, RF, CCdA, Rocca, Serafim, AdP, et al. (2023) Cogntiive impairment in long-COVID and its association with persistent dysregulation in inflammatory markers. Frontiers in Immunology 14, 1174020. DOI: 10.3389/fimmu.2023.1174020.CrossRefGoogle Scholar
de Wit, L, Have, MT, Cuijpers, P, et al. (2022) Body Mass Index and risk for onset of mood and anxiety disorders in the general population: results from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2). BMC Psychiatry 22(1), 522. DOI: 10.1186/s12888-022-04077-w.CrossRefGoogle ScholarPubMed
Elias, MF, Elias, PK, Sullivan, LM, et al. (2005) Obesity, diabetes and cognitive deficit: The Framingham Heart Study. Neurobiology of Aging 26(1), 11–16. DOI: 10.1016/j.neurobiolaging.2005.08.019.CrossRefGoogle ScholarPubMed
Ellulu, MS, Patimah, I, Khaza’ai, H, et al. (2017) Obesity and inflammation: the linking mechanism and the complications. Archives of Medical Science 13(4), 851–863. DOI: 10.5114/aoms.2016.58928.CrossRefGoogle ScholarPubMed
Foulkes, A, Selvaggi, C, Shinnick, D, et al. (2022) Understanding the link between obesity and severe COVID-19 outcomes: Causal mediation by systemic inflammatory response. The Journal of Clinical Endocrinology & Metabolism 107(2), e698–707. DOI: 10.1210/clinem/dgab629.CrossRefGoogle ScholarPubMed
Frere, JJ, Serafini, RA, Pryce, KD, et al. (2022) SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after recover. Science Translational Medicine 14(664), eabq3059. DOI: 10.1126/scitranslmed.abq3059.CrossRefGoogle Scholar
He, D, Yuan, M, Dang, W, et al. (2023) Long term neuropsychiatric consequences in COVID-19 survivors: cognitive impairment and inflammatory underpinnings fifteen months after discharge. Asian Journal of Psychiatry 80, 103409. DOI: 10.1016/j.ajp.2022.103409.CrossRefGoogle ScholarPubMed
International Council For Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). Integrated addendum to ICH E6(R1)(2016). Guideline for good clinical practice. https://database.ich.org/ (accessed 9.25.23).Google Scholar
Jaeger, J (2018) Digit symbol substitution test: the case for sensitivity over specificity in neuropsychological testing. Journal of Clinical Psychopharmacology 28(5), 513–519. DOI: 10.1097/JCP.0000000000000941.CrossRefGoogle Scholar
Jang, D, Lee, AH, Shin, HY, et al. (2021) The role of tumor necrosis factor alpha (TNF-ɑ) in autoimmune disease and current TNF-ɑ inhibitors in therapeutics. International Journal of Molecular Sciences 22(5), 2719. DOI: 10.3390/ijms22052719.CrossRefGoogle ScholarPubMed
Khanmohammadi, S and Rezaei, N (2021) Role of Toll-like receptors in the pathogenesis of COVID-19. Journal of Medical Virology 93(5), 2735–2739. DOI: 10.1002/jmv.26826.CrossRefGoogle ScholarPubMed
Kim, S, Kim, Y and Park, SM (2016) Body mass index and decline of cognitive function. PLoS One 11(2), e0148908. DOI: 10.1371/journal.pone.0148908.CrossRefGoogle ScholarPubMed
Klein, R, Soung, A, Sissoko, C, et al. (2021) COVID-19 induces neuroinflammation and loss of hippocampal neurogenesis. Res Sq. rs.3.rs-1031824 [Preprint]. DOI: 10.21203/rs.3.rs-1031824/v1.Google ScholarPubMed
Lechner-Scott, J, Levy, M, Hawkes, C, et al. (2021) Long covid or post covid-19 syndrome. Multiple Sclerosis and Related Disorders 55, 103268. DOI: 10.1016/j.msard.2021.103268.CrossRefGoogle ScholarPubMed
Longo, M, Zatterale, F, Naderi, J, Parrillo, L, Formisano, P, Raciti, GA, Beguinot, F and Miele, C (2019) Adipose tissue dysfunction as determinant of obesity-associated metabolic complications. International Journal of Molecular Sciences 20(9), 2358. DOI: 10.3390/ijms20092358.CrossRefGoogle ScholarPubMed
McIntyre, RS, Mansur, RB, Lee, Y, et al. (2017) Adverse effects of obesity on cognitive functions in individuals at ultra high risk for bipolar disorder: results from the global mood and brain science initiative. Bipolar Disorders 19(2), 128–134. DOI: 10.1111/bdi.12491.CrossRefGoogle ScholarPubMed
McIntyre, RS, Phan, L, Kwan, ATH, et al. (2023) Vortioxetine for the treatment of post-COVID-19 condition: a randomized controlled trial. Brain 147(3), 849–857. DOI: 10.1093/brain/awad377.CrossRefGoogle Scholar
McNeill, JN, Lau, ES, Paniagua, SM, et al. (2021) The role of obesity in inflammatory markers in COVID-19 patients. Obesity Research & Clinical Practice 15(1), 96–99. DOI: 10.1016/j.orcp.2020.12.004.CrossRefGoogle ScholarPubMed
Michaud, TL, Siahpush, M, Farazi, PA, et al. (2018) The association between body mass index, and cognitive, functional, and behavioral declines for incident dementia. Journal of Alzheimers Disease 66(4), 1507–1517. DOI: 10.3233/JAD-180278.CrossRefGoogle ScholarPubMed
Miller, AA and Spencer, SJ (2014) Obesity and neuroinflammation: a pathway to cognitive impairment. Brain, Behavior, and Immunity 42, 10–21. DOI: 10.1016/j.bbi.2014.04.001.CrossRefGoogle ScholarPubMed
Misiak, B, Leszek, J and Kiejna, A (2012) Metabolic syndrome, mild cognitive impairment and Alzheimer’s disease--the emerging role of systemic low-grade inflammation and adiposity. Brain Research Bulletin 89(3-4), 144–149. DOI: 10.1016/j.brainresbull.2012.08.003.CrossRefGoogle ScholarPubMed
Peaker, A and Steward, LE (1989) Rey’s auditory verbal learning test – a review. Developments in Clinical and Experimental Neuropsychology, 219–236. DOI: 10.1007/978-1-4757-9996-5_18.CrossRefGoogle Scholar
Popko, K, Gorska, E, Stelmaszczyk-Emmel, A, et al. (2010) Proinflammatory cytokiens IL-6 and TNF-a and the development of inflammation in obese subjects. European Journal of Medical Research 15(S2), 120. DOI: 10.1186/2047-783X-15-S2-120.CrossRefGoogle Scholar
Port, JR, Adney, DR, Schwarz, B, et al. (2021) High-fat high-sugar diet-induced changes in the lipid metabolism are associated with mildly increased COVID-19 severity and delayed recovery in the Syrian hamster. Viruses 13(12), 2506. DOI: 10.3390/v13122506.CrossRefGoogle ScholarPubMed
Quinn, KL, Katz, GM, Bobos, P, et al. (2022) Understanding the post covid-19 condition (long covid) in adults and the expected burden for Ontario. Ontario COVID-19 Science Advisory Table. DOI: 10.47326/ocsat.2022.03.65.1.0.Google Scholar
Samara, A, Murphy, T, Strain, J, et al. (2019) Neuroinflammation and white matter alterations in obesity assessed by diffusion basis spectrum imaging. Frontiers in Human Neuroscience 13, 464. DOI: 10.3389/fnhum.2019.00464.CrossRefGoogle ScholarPubMed
Song, W, Hui, CK, Hull, JH, et al. (2021) Confronting covid-19-associated cough and the post-covid syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses. The Lancet Respiratory Medicine. 9(5), 533–544. DOI: 10.1016/s2213-2600(21)00125-9.CrossRefGoogle ScholarPubMed
Soriano, JB, Murthy, S, Marshall, JC, et al. (2022) A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infectious Diseases 22(4), e102–e107. DOI: 10.1016/S1473-3099(21)00703-9.CrossRefGoogle ScholarPubMed
Subramanian, A, Nirantharakumar, K, Hughes, S, et al. (2022) Symptoms and risk factors for long covid in non-hospitalized adults. Nature Medicine 28(8), 1706–1714. DOI: 10.1038/s41591-022-01909-w.CrossRefGoogle ScholarPubMed
Sudre, CH, Murray, B, Varsavsky, T, et al. (2021) Attributes and predictors of long COVID. Nature Medicine 27(4), 626–631. DOI: 10.1038/s41591-021-01292-y.CrossRefGoogle ScholarPubMed
Theoharides, TC, Steward, JM, Hatziagelaki, E, et al. (2015) Brain “fog”, inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin. Frontiers in Neuroscience 9, 225. DOI: 10.3389/fnins.2015.00225.CrossRefGoogle ScholarPubMed
Thiara, G, Cigliobianco, M, Muravsky, A, et al. (2017) Evidence for neurocognitive improvement after bariatric surgery: a systematic review. Psychosomatics 58(3), 217–227. DOI: 10.1016/j.psym.2017.02.004.CrossRefGoogle ScholarPubMed
Tombaugh, TM (2004) Trail making test A and B: normative data stratified by age and education. Archives of Clinical Neuropsychology 19(2), 203–214. DOI: 10.1016/S0887-6177(03)00039-8.CrossRefGoogle Scholar
Vgontzas, AN, Bixler, EO and Chrousos, GP (2006) Obesity-related sleepiness and fatigue: the role of the stress system and cytokines. Annals of the New York Academy of Sciences 1083(1), 329–344. DOI: 10.1196/annals.1367.023.CrossRefGoogle ScholarPubMed
Vimercati, L, de Maria, L, Quarato, M, et al. (2021) Association between long COVID and overweight/obesity. Journal of Clinical Medicine 10(18), 4143. DOI: 10.3390/jcm10184143.CrossRefGoogle ScholarPubMed
WMA – The World Medical Association (2008) Declaration of Helsinki. https://www.wma.net/what-we-do/medical-ethics/declaration-of-helsinki/doh-oct2008/ (accessed 25 September 2023).Google Scholar
WHO (n.d.) World Health Organization – WHO Coronavirus (COVID-19) dashboard [Internet]. [cited 2023 April 1]. https://covid19.who.int/ Google Scholar
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