Catriona Syme1,2, Stephanie Pelletier1,2, Jean Shin1,2, Michal Abrahamowicz3, Gabriel Leonard4, Michel Perron5, Louis Richer6, Suzanne Veillette5, Daniel Gaudet7, Bruce Pike8, Lisa J Strug1,9, Yun Wang10, Hongbin Xu10, Graeme Taylor10, Steffany Bennett10, Tomas Paus11,12, Zdenka Pausova13,14. 1. The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. 2. Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, ON, Canada. 3. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada. 4. Montreal Neurological Institute, McGill University, Montreal, QC, Canada. 5. Department of Human Sciences, Université du Québec à Chicoutimi, Chicoutimi, QC, Canada. 6. Department of Health Sciences, Université du Québec à Chicoutimi, Chicoutimi, QC, Canada. 7. Community Genomic Centre, Université de Montréal, Chicoutimi, QC, Canada. 8. Department of Radiology and Clinical Neurosciences, University of Calgary, Calgary, AB, Canada. 9. Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. 10. Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON, Canada. 11. Bloorview Research Institute, Toronto, ON, Canada. 12. Departments of Psychology and Psychiatry, University of Toronto, Toronto, ON, Canada. 13. The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. zdenka.pausova@sickkids.ca. 14. Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, ON, Canada. zdenka.pausova@sickkids.ca.
Abstract
OBJECTIVE: Life-long maintenance of brain health is important for the prevention of cognitive impairment in older age. Low-grade peripheral inflammation associated with excess visceral fat (VF) may influence brain structure and function. Here we examined (i) if this type of inflammation is associated with altered white-matter (WM) microstructure and lower cognitive functioning in adolescents, and (ii) if recently identified circulating glycerophosphocholines (GPCs) can index this type of inflammation and associated variations in WM microstructure and cognitive functioning. SUBJECTS: We studied a community-based sample of 872 adolescents (12-18 years, 48% males) in whom we assessed VF and WM microstructure with magnetic resonance imaging, processing speed with cognitive testing, serum C-reactive protein (CRP, a common marker of peripheral inflammation) with a high-sensitivity assay, and serum levels of a panel of 64 GPCs with advanced mass spectrometry. RESULTS: VF was associated with CRP, and CRP in turn was associated with "altered" WM microstructure and lower processing speed (all p < 0.003). Further, "altered" WM microstructure was associated with lower processing speed (p < 0.0001). Of all 64 tested GPCs, 4 were associated with both VF and CRP (at Bonferroni corrected p < 0.0004). One of them, PC16:0/2:0, was also associated with WM microstructure (p < 0.0001) and processing speed (p = 0.0003), and mediated the directed associations between VF and both WM microstructure (p < 0.0001) and processing speed (p = 0.02). As a mediator, PC16:0/2:0 explained 21% of shared variance between VF and WM microstructure, and 22% of shared variance between VF and processing speed. Similar associations were observed in an auxiliary study of 80 middle-aged adults. CONCLUSIONS: Our results show that VF-related peripheral inflammation is associated with "altered" WM microstructure and lower cognitive functioning already in adolescents, and a specific circulating GPC may be a new molecule indexing this VF-related peripheral inflammation and its influences on brain structure and function.
OBJECTIVE: Life-long maintenance of brain health is important for the prevention of cognitive impairment in older age. Low-grade peripheral inflammation associated with excess visceral fat (VF) may influence brain structure and function. Here we examined (i) if this type of inflammation is associated with altered white-matter (WM) microstructure and lower cognitive functioning in adolescents, and (ii) if recently identified circulating glycerophosphocholines (GPCs) can index this type of inflammation and associated variations in WM microstructure and cognitive functioning. SUBJECTS: We studied a community-based sample of 872 adolescents (12-18 years, 48% males) in whom we assessed VF and WM microstructure with magnetic resonance imaging, processing speed with cognitive testing, serum C-reactive protein (CRP, a common marker of peripheral inflammation) with a high-sensitivity assay, and serum levels of a panel of 64 GPCs with advanced mass spectrometry. RESULTS: VF was associated with CRP, and CRP in turn was associated with "altered" WM microstructure and lower processing speed (all p < 0.003). Further, "altered" WM microstructure was associated with lower processing speed (p < 0.0001). Of all 64 tested GPCs, 4 were associated with both VF and CRP (at Bonferroni corrected p < 0.0004). One of them, PC16:0/2:0, was also associated with WM microstructure (p < 0.0001) and processing speed (p = 0.0003), and mediated the directed associations between VF and both WM microstructure (p < 0.0001) and processing speed (p = 0.02). As a mediator, PC16:0/2:0 explained 21% of shared variance between VF and WM microstructure, and 22% of shared variance between VF and processing speed. Similar associations were observed in an auxiliary study of 80 middle-aged adults. CONCLUSIONS: Our results show that VF-related peripheral inflammation is associated with "altered" WM microstructure and lower cognitive functioning already in adolescents, and a specific circulating GPC may be a new molecule indexing this VF-related peripheral inflammation and its influences on brain structure and function.
Authors: Sonia S Anand; Matthias G Friedrich; Douglas S Lee; Phillip Awadalla; J P Després; Dipika Desai; Russell J de Souza; Trevor Dummer; Grace Parraga; Eric Larose; Scott A Lear; Koon K Teo; Paul Poirier; Karleen M Schulze; Dorota Szczesniak; Jean-Claude Tardif; Jennifer Vena; Katarzyna Zatonska; Salim Yusuf; Eric E Smith Journal: JAMA Netw Open Date: 2022-02-01