Systemic inflammatory markers in relation to cognitive function and measures of brain atrophy: a Mendelian randomization study
Abstract Observational studies have implied associations between multiple cytokines and cognitive decline, anti-inflammatory drugs however did not yield any protective effects on cognitive decline. We aimed to assess the associations of systemic inflammation, as measured by multiple cytokine and gro...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Luo, Jiao [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2022 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s) 2022 |
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| Übergeordnetes Werk: |
Enthalten in: Age - New York, NY : Springer Science+Business Media, 1978, 44(2022), 4 vom: 11. Juni, Seite 2259-2270 |
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| Übergeordnetes Werk: |
volume:44 ; year:2022 ; number:4 ; day:11 ; month:06 ; pages:2259-2270 |
| Links: |
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| DOI / URN: |
10.1007/s11357-022-00602-7 |
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| Katalog-ID: |
SPR048482609 |
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| 520 | |a Abstract Observational studies have implied associations between multiple cytokines and cognitive decline, anti-inflammatory drugs however did not yield any protective effects on cognitive decline. We aimed to assess the associations of systemic inflammation, as measured by multiple cytokine and growth factor, with cognitive performance and brain atrophy using two-sample Mendelian randomization (MR). Independent genetic instruments (p < 5e − 8 and p < 5e − 6) for 41 systemic inflammatory markers were retrieved from a genome-wide association study conducted in 8293 Finnish participants. Summary statistics for gene-outcome associations were obtained for cognitive performance (N = 257,841) and for brain atrophy measures of cerebral cortical surface area and thickness (N = 51,665) and hippocampal volume (N = 33,536). To rule out the heterogeneity in the cognitive performance, we additionally included three domains: the fluid intelligence score (N = 108,818), prospective memory result (N = 111,099), and reaction time (N = 330,069). Main results were computed by inverse-variance weighting; sensitivity analyses taking pleiotropy and invalid instruments into account were performed by using weighted-median estimator, MR-Egger, and MR PRESSO. After correcting for multiple testing using false discovery rate, only genetically predicted (with p < 5e − 6 threshold) per-SD (standard deviation) higher IL-8 was associated with − 0.103 (− 0.155, − 0.051, padjusted = 0.004) $ mm^{3} $ smaller hippocampal volume and higher intelligence fluid score [β: 0.103 SD (95% CI: 0.042, 0.165), padjusted = 0.041]. Sensitivity analyses generally showed similar results, and no pleiotropic effect, heterogeneity, or possible reverse causation was detected. Our results suggested a possible causal association of high IL-8 levels with better cognitive performance but smaller hippocampal volume among the general healthy population, highlighting the complex role of inflammation in dementia-related phenotypes. Further research is needed to elucidate mechanisms underlying these associations. | ||
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10.1007/s11357-022-00602-7 doi (DE-627)SPR048482609 (SPR)s11357-022-00602-7-e DE-627 ger DE-627 rakwb eng Luo, Jiao verfasserin (orcid)0000-0001-8511-8945 aut Systemic inflammatory markers in relation to cognitive function and measures of brain atrophy: a Mendelian randomization study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Abstract Observational studies have implied associations between multiple cytokines and cognitive decline, anti-inflammatory drugs however did not yield any protective effects on cognitive decline. We aimed to assess the associations of systemic inflammation, as measured by multiple cytokine and growth factor, with cognitive performance and brain atrophy using two-sample Mendelian randomization (MR). Independent genetic instruments (p < 5e − 8 and p < 5e − 6) for 41 systemic inflammatory markers were retrieved from a genome-wide association study conducted in 8293 Finnish participants. Summary statistics for gene-outcome associations were obtained for cognitive performance (N = 257,841) and for brain atrophy measures of cerebral cortical surface area and thickness (N = 51,665) and hippocampal volume (N = 33,536). To rule out the heterogeneity in the cognitive performance, we additionally included three domains: the fluid intelligence score (N = 108,818), prospective memory result (N = 111,099), and reaction time (N = 330,069). Main results were computed by inverse-variance weighting; sensitivity analyses taking pleiotropy and invalid instruments into account were performed by using weighted-median estimator, MR-Egger, and MR PRESSO. After correcting for multiple testing using false discovery rate, only genetically predicted (with p < 5e − 6 threshold) per-SD (standard deviation) higher IL-8 was associated with − 0.103 (− 0.155, − 0.051, padjusted = 0.004) $ mm^{3} $ smaller hippocampal volume and higher intelligence fluid score [β: 0.103 SD (95% CI: 0.042, 0.165), padjusted = 0.041]. Sensitivity analyses generally showed similar results, and no pleiotropic effect, heterogeneity, or possible reverse causation was detected. Our results suggested a possible causal association of high IL-8 levels with better cognitive performance but smaller hippocampal volume among the general healthy population, highlighting the complex role of inflammation in dementia-related phenotypes. Further research is needed to elucidate mechanisms underlying these associations. Inflammation (dpeaa)DE-He213 Cytokines (dpeaa)DE-He213 Cognitive function (dpeaa)DE-He213 Hippocampal volume (dpeaa)DE-He213 Cerebral cortex (dpeaa)DE-He213 le Cessie, Saskia aut Blauw, Gerard Jan aut Franceschi, Claudio aut Noordam, Raymond aut van Heemst, Diana aut Enthalten in Age New York, NY : Springer Science+Business Media, 1978 44(2022), 4 vom: 11. Juni, Seite 2259-2270 (DE-627)499546180 (DE-600)2201958-3 1574-4647 nnns volume:44 year:2022 number:4 day:11 month:06 pages:2259-2270 https://dx.doi.org/10.1007/s11357-022-00602-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_40 GBV_ILN_60 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_110 GBV_ILN_120 GBV_ILN_161 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 AR 44 2022 4 11 06 2259-2270 |
| spelling |
10.1007/s11357-022-00602-7 doi (DE-627)SPR048482609 (SPR)s11357-022-00602-7-e DE-627 ger DE-627 rakwb eng Luo, Jiao verfasserin (orcid)0000-0001-8511-8945 aut Systemic inflammatory markers in relation to cognitive function and measures of brain atrophy: a Mendelian randomization study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Abstract Observational studies have implied associations between multiple cytokines and cognitive decline, anti-inflammatory drugs however did not yield any protective effects on cognitive decline. We aimed to assess the associations of systemic inflammation, as measured by multiple cytokine and growth factor, with cognitive performance and brain atrophy using two-sample Mendelian randomization (MR). Independent genetic instruments (p < 5e − 8 and p < 5e − 6) for 41 systemic inflammatory markers were retrieved from a genome-wide association study conducted in 8293 Finnish participants. Summary statistics for gene-outcome associations were obtained for cognitive performance (N = 257,841) and for brain atrophy measures of cerebral cortical surface area and thickness (N = 51,665) and hippocampal volume (N = 33,536). To rule out the heterogeneity in the cognitive performance, we additionally included three domains: the fluid intelligence score (N = 108,818), prospective memory result (N = 111,099), and reaction time (N = 330,069). Main results were computed by inverse-variance weighting; sensitivity analyses taking pleiotropy and invalid instruments into account were performed by using weighted-median estimator, MR-Egger, and MR PRESSO. After correcting for multiple testing using false discovery rate, only genetically predicted (with p < 5e − 6 threshold) per-SD (standard deviation) higher IL-8 was associated with − 0.103 (− 0.155, − 0.051, padjusted = 0.004) $ mm^{3} $ smaller hippocampal volume and higher intelligence fluid score [β: 0.103 SD (95% CI: 0.042, 0.165), padjusted = 0.041]. Sensitivity analyses generally showed similar results, and no pleiotropic effect, heterogeneity, or possible reverse causation was detected. Our results suggested a possible causal association of high IL-8 levels with better cognitive performance but smaller hippocampal volume among the general healthy population, highlighting the complex role of inflammation in dementia-related phenotypes. Further research is needed to elucidate mechanisms underlying these associations. Inflammation (dpeaa)DE-He213 Cytokines (dpeaa)DE-He213 Cognitive function (dpeaa)DE-He213 Hippocampal volume (dpeaa)DE-He213 Cerebral cortex (dpeaa)DE-He213 le Cessie, Saskia aut Blauw, Gerard Jan aut Franceschi, Claudio aut Noordam, Raymond aut van Heemst, Diana aut Enthalten in Age New York, NY : Springer Science+Business Media, 1978 44(2022), 4 vom: 11. Juni, Seite 2259-2270 (DE-627)499546180 (DE-600)2201958-3 1574-4647 nnns volume:44 year:2022 number:4 day:11 month:06 pages:2259-2270 https://dx.doi.org/10.1007/s11357-022-00602-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_40 GBV_ILN_60 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_110 GBV_ILN_120 GBV_ILN_161 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 AR 44 2022 4 11 06 2259-2270 |
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10.1007/s11357-022-00602-7 doi (DE-627)SPR048482609 (SPR)s11357-022-00602-7-e DE-627 ger DE-627 rakwb eng Luo, Jiao verfasserin (orcid)0000-0001-8511-8945 aut Systemic inflammatory markers in relation to cognitive function and measures of brain atrophy: a Mendelian randomization study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Abstract Observational studies have implied associations between multiple cytokines and cognitive decline, anti-inflammatory drugs however did not yield any protective effects on cognitive decline. We aimed to assess the associations of systemic inflammation, as measured by multiple cytokine and growth factor, with cognitive performance and brain atrophy using two-sample Mendelian randomization (MR). Independent genetic instruments (p < 5e − 8 and p < 5e − 6) for 41 systemic inflammatory markers were retrieved from a genome-wide association study conducted in 8293 Finnish participants. Summary statistics for gene-outcome associations were obtained for cognitive performance (N = 257,841) and for brain atrophy measures of cerebral cortical surface area and thickness (N = 51,665) and hippocampal volume (N = 33,536). To rule out the heterogeneity in the cognitive performance, we additionally included three domains: the fluid intelligence score (N = 108,818), prospective memory result (N = 111,099), and reaction time (N = 330,069). Main results were computed by inverse-variance weighting; sensitivity analyses taking pleiotropy and invalid instruments into account were performed by using weighted-median estimator, MR-Egger, and MR PRESSO. After correcting for multiple testing using false discovery rate, only genetically predicted (with p < 5e − 6 threshold) per-SD (standard deviation) higher IL-8 was associated with − 0.103 (− 0.155, − 0.051, padjusted = 0.004) $ mm^{3} $ smaller hippocampal volume and higher intelligence fluid score [β: 0.103 SD (95% CI: 0.042, 0.165), padjusted = 0.041]. Sensitivity analyses generally showed similar results, and no pleiotropic effect, heterogeneity, or possible reverse causation was detected. Our results suggested a possible causal association of high IL-8 levels with better cognitive performance but smaller hippocampal volume among the general healthy population, highlighting the complex role of inflammation in dementia-related phenotypes. Further research is needed to elucidate mechanisms underlying these associations. Inflammation (dpeaa)DE-He213 Cytokines (dpeaa)DE-He213 Cognitive function (dpeaa)DE-He213 Hippocampal volume (dpeaa)DE-He213 Cerebral cortex (dpeaa)DE-He213 le Cessie, Saskia aut Blauw, Gerard Jan aut Franceschi, Claudio aut Noordam, Raymond aut van Heemst, Diana aut Enthalten in Age New York, NY : Springer Science+Business Media, 1978 44(2022), 4 vom: 11. Juni, Seite 2259-2270 (DE-627)499546180 (DE-600)2201958-3 1574-4647 nnns volume:44 year:2022 number:4 day:11 month:06 pages:2259-2270 https://dx.doi.org/10.1007/s11357-022-00602-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_40 GBV_ILN_60 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_110 GBV_ILN_120 GBV_ILN_161 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 AR 44 2022 4 11 06 2259-2270 |
| allfieldsGer |
10.1007/s11357-022-00602-7 doi (DE-627)SPR048482609 (SPR)s11357-022-00602-7-e DE-627 ger DE-627 rakwb eng Luo, Jiao verfasserin (orcid)0000-0001-8511-8945 aut Systemic inflammatory markers in relation to cognitive function and measures of brain atrophy: a Mendelian randomization study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Abstract Observational studies have implied associations between multiple cytokines and cognitive decline, anti-inflammatory drugs however did not yield any protective effects on cognitive decline. We aimed to assess the associations of systemic inflammation, as measured by multiple cytokine and growth factor, with cognitive performance and brain atrophy using two-sample Mendelian randomization (MR). Independent genetic instruments (p < 5e − 8 and p < 5e − 6) for 41 systemic inflammatory markers were retrieved from a genome-wide association study conducted in 8293 Finnish participants. Summary statistics for gene-outcome associations were obtained for cognitive performance (N = 257,841) and for brain atrophy measures of cerebral cortical surface area and thickness (N = 51,665) and hippocampal volume (N = 33,536). To rule out the heterogeneity in the cognitive performance, we additionally included three domains: the fluid intelligence score (N = 108,818), prospective memory result (N = 111,099), and reaction time (N = 330,069). Main results were computed by inverse-variance weighting; sensitivity analyses taking pleiotropy and invalid instruments into account were performed by using weighted-median estimator, MR-Egger, and MR PRESSO. After correcting for multiple testing using false discovery rate, only genetically predicted (with p < 5e − 6 threshold) per-SD (standard deviation) higher IL-8 was associated with − 0.103 (− 0.155, − 0.051, padjusted = 0.004) $ mm^{3} $ smaller hippocampal volume and higher intelligence fluid score [β: 0.103 SD (95% CI: 0.042, 0.165), padjusted = 0.041]. Sensitivity analyses generally showed similar results, and no pleiotropic effect, heterogeneity, or possible reverse causation was detected. Our results suggested a possible causal association of high IL-8 levels with better cognitive performance but smaller hippocampal volume among the general healthy population, highlighting the complex role of inflammation in dementia-related phenotypes. Further research is needed to elucidate mechanisms underlying these associations. Inflammation (dpeaa)DE-He213 Cytokines (dpeaa)DE-He213 Cognitive function (dpeaa)DE-He213 Hippocampal volume (dpeaa)DE-He213 Cerebral cortex (dpeaa)DE-He213 le Cessie, Saskia aut Blauw, Gerard Jan aut Franceschi, Claudio aut Noordam, Raymond aut van Heemst, Diana aut Enthalten in Age New York, NY : Springer Science+Business Media, 1978 44(2022), 4 vom: 11. Juni, Seite 2259-2270 (DE-627)499546180 (DE-600)2201958-3 1574-4647 nnns volume:44 year:2022 number:4 day:11 month:06 pages:2259-2270 https://dx.doi.org/10.1007/s11357-022-00602-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_40 GBV_ILN_60 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_110 GBV_ILN_120 GBV_ILN_161 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 AR 44 2022 4 11 06 2259-2270 |
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10.1007/s11357-022-00602-7 doi (DE-627)SPR048482609 (SPR)s11357-022-00602-7-e DE-627 ger DE-627 rakwb eng Luo, Jiao verfasserin (orcid)0000-0001-8511-8945 aut Systemic inflammatory markers in relation to cognitive function and measures of brain atrophy: a Mendelian randomization study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Abstract Observational studies have implied associations between multiple cytokines and cognitive decline, anti-inflammatory drugs however did not yield any protective effects on cognitive decline. We aimed to assess the associations of systemic inflammation, as measured by multiple cytokine and growth factor, with cognitive performance and brain atrophy using two-sample Mendelian randomization (MR). Independent genetic instruments (p < 5e − 8 and p < 5e − 6) for 41 systemic inflammatory markers were retrieved from a genome-wide association study conducted in 8293 Finnish participants. Summary statistics for gene-outcome associations were obtained for cognitive performance (N = 257,841) and for brain atrophy measures of cerebral cortical surface area and thickness (N = 51,665) and hippocampal volume (N = 33,536). To rule out the heterogeneity in the cognitive performance, we additionally included three domains: the fluid intelligence score (N = 108,818), prospective memory result (N = 111,099), and reaction time (N = 330,069). Main results were computed by inverse-variance weighting; sensitivity analyses taking pleiotropy and invalid instruments into account were performed by using weighted-median estimator, MR-Egger, and MR PRESSO. After correcting for multiple testing using false discovery rate, only genetically predicted (with p < 5e − 6 threshold) per-SD (standard deviation) higher IL-8 was associated with − 0.103 (− 0.155, − 0.051, padjusted = 0.004) $ mm^{3} $ smaller hippocampal volume and higher intelligence fluid score [β: 0.103 SD (95% CI: 0.042, 0.165), padjusted = 0.041]. Sensitivity analyses generally showed similar results, and no pleiotropic effect, heterogeneity, or possible reverse causation was detected. Our results suggested a possible causal association of high IL-8 levels with better cognitive performance but smaller hippocampal volume among the general healthy population, highlighting the complex role of inflammation in dementia-related phenotypes. Further research is needed to elucidate mechanisms underlying these associations. Inflammation (dpeaa)DE-He213 Cytokines (dpeaa)DE-He213 Cognitive function (dpeaa)DE-He213 Hippocampal volume (dpeaa)DE-He213 Cerebral cortex (dpeaa)DE-He213 le Cessie, Saskia aut Blauw, Gerard Jan aut Franceschi, Claudio aut Noordam, Raymond aut van Heemst, Diana aut Enthalten in Age New York, NY : Springer Science+Business Media, 1978 44(2022), 4 vom: 11. Juni, Seite 2259-2270 (DE-627)499546180 (DE-600)2201958-3 1574-4647 nnns volume:44 year:2022 number:4 day:11 month:06 pages:2259-2270 https://dx.doi.org/10.1007/s11357-022-00602-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_40 GBV_ILN_60 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_110 GBV_ILN_120 GBV_ILN_161 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 AR 44 2022 4 11 06 2259-2270 |
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Luo, Jiao |
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systemic inflammatory markers in relation to cognitive function and measures of brain atrophy: a mendelian randomization study |
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Systemic inflammatory markers in relation to cognitive function and measures of brain atrophy: a Mendelian randomization study |
| abstract |
Abstract Observational studies have implied associations between multiple cytokines and cognitive decline, anti-inflammatory drugs however did not yield any protective effects on cognitive decline. We aimed to assess the associations of systemic inflammation, as measured by multiple cytokine and growth factor, with cognitive performance and brain atrophy using two-sample Mendelian randomization (MR). Independent genetic instruments (p < 5e − 8 and p < 5e − 6) for 41 systemic inflammatory markers were retrieved from a genome-wide association study conducted in 8293 Finnish participants. Summary statistics for gene-outcome associations were obtained for cognitive performance (N = 257,841) and for brain atrophy measures of cerebral cortical surface area and thickness (N = 51,665) and hippocampal volume (N = 33,536). To rule out the heterogeneity in the cognitive performance, we additionally included three domains: the fluid intelligence score (N = 108,818), prospective memory result (N = 111,099), and reaction time (N = 330,069). Main results were computed by inverse-variance weighting; sensitivity analyses taking pleiotropy and invalid instruments into account were performed by using weighted-median estimator, MR-Egger, and MR PRESSO. After correcting for multiple testing using false discovery rate, only genetically predicted (with p < 5e − 6 threshold) per-SD (standard deviation) higher IL-8 was associated with − 0.103 (− 0.155, − 0.051, padjusted = 0.004) $ mm^{3} $ smaller hippocampal volume and higher intelligence fluid score [β: 0.103 SD (95% CI: 0.042, 0.165), padjusted = 0.041]. Sensitivity analyses generally showed similar results, and no pleiotropic effect, heterogeneity, or possible reverse causation was detected. Our results suggested a possible causal association of high IL-8 levels with better cognitive performance but smaller hippocampal volume among the general healthy population, highlighting the complex role of inflammation in dementia-related phenotypes. Further research is needed to elucidate mechanisms underlying these associations. © The Author(s) 2022 |
| abstractGer |
Abstract Observational studies have implied associations between multiple cytokines and cognitive decline, anti-inflammatory drugs however did not yield any protective effects on cognitive decline. We aimed to assess the associations of systemic inflammation, as measured by multiple cytokine and growth factor, with cognitive performance and brain atrophy using two-sample Mendelian randomization (MR). Independent genetic instruments (p < 5e − 8 and p < 5e − 6) for 41 systemic inflammatory markers were retrieved from a genome-wide association study conducted in 8293 Finnish participants. Summary statistics for gene-outcome associations were obtained for cognitive performance (N = 257,841) and for brain atrophy measures of cerebral cortical surface area and thickness (N = 51,665) and hippocampal volume (N = 33,536). To rule out the heterogeneity in the cognitive performance, we additionally included three domains: the fluid intelligence score (N = 108,818), prospective memory result (N = 111,099), and reaction time (N = 330,069). Main results were computed by inverse-variance weighting; sensitivity analyses taking pleiotropy and invalid instruments into account were performed by using weighted-median estimator, MR-Egger, and MR PRESSO. After correcting for multiple testing using false discovery rate, only genetically predicted (with p < 5e − 6 threshold) per-SD (standard deviation) higher IL-8 was associated with − 0.103 (− 0.155, − 0.051, padjusted = 0.004) $ mm^{3} $ smaller hippocampal volume and higher intelligence fluid score [β: 0.103 SD (95% CI: 0.042, 0.165), padjusted = 0.041]. Sensitivity analyses generally showed similar results, and no pleiotropic effect, heterogeneity, or possible reverse causation was detected. Our results suggested a possible causal association of high IL-8 levels with better cognitive performance but smaller hippocampal volume among the general healthy population, highlighting the complex role of inflammation in dementia-related phenotypes. Further research is needed to elucidate mechanisms underlying these associations. © The Author(s) 2022 |
| abstract_unstemmed |
Abstract Observational studies have implied associations between multiple cytokines and cognitive decline, anti-inflammatory drugs however did not yield any protective effects on cognitive decline. We aimed to assess the associations of systemic inflammation, as measured by multiple cytokine and growth factor, with cognitive performance and brain atrophy using two-sample Mendelian randomization (MR). Independent genetic instruments (p < 5e − 8 and p < 5e − 6) for 41 systemic inflammatory markers were retrieved from a genome-wide association study conducted in 8293 Finnish participants. Summary statistics for gene-outcome associations were obtained for cognitive performance (N = 257,841) and for brain atrophy measures of cerebral cortical surface area and thickness (N = 51,665) and hippocampal volume (N = 33,536). To rule out the heterogeneity in the cognitive performance, we additionally included three domains: the fluid intelligence score (N = 108,818), prospective memory result (N = 111,099), and reaction time (N = 330,069). Main results were computed by inverse-variance weighting; sensitivity analyses taking pleiotropy and invalid instruments into account were performed by using weighted-median estimator, MR-Egger, and MR PRESSO. After correcting for multiple testing using false discovery rate, only genetically predicted (with p < 5e − 6 threshold) per-SD (standard deviation) higher IL-8 was associated with − 0.103 (− 0.155, − 0.051, padjusted = 0.004) $ mm^{3} $ smaller hippocampal volume and higher intelligence fluid score [β: 0.103 SD (95% CI: 0.042, 0.165), padjusted = 0.041]. Sensitivity analyses generally showed similar results, and no pleiotropic effect, heterogeneity, or possible reverse causation was detected. Our results suggested a possible causal association of high IL-8 levels with better cognitive performance but smaller hippocampal volume among the general healthy population, highlighting the complex role of inflammation in dementia-related phenotypes. Further research is needed to elucidate mechanisms underlying these associations. © The Author(s) 2022 |
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Systemic inflammatory markers in relation to cognitive function and measures of brain atrophy: a Mendelian randomization study |
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le Cessie, Saskia Blauw, Gerard Jan Franceschi, Claudio Noordam, Raymond van Heemst, Diana |
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