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Decomposing interaction and mediating effects of race/ethnicity and circulating blood levels of cystatin C on cognitive status in the United States health and retirement study

BACKGROUND AND OBJECTIVES: Elevated circulating cystatin C is associated with cognitive impairment in non-Hispanic Whites, but its role in racial disparities in dementia is understudied. In a nationally representative sample of older non-Hispanic White, non-Hispanic Black, and Hispanic adults in the...

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Autores principales: Higgins Tejera, César, Ware, Erin B., Kobayashi, Lindsay C., Fu, Mingzhou, Hicken, Margaret, Zawistowski, Matthew, Mukherjee, Bhramar, Bakulski, Kelly M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267311/
https://www.ncbi.nlm.nih.gov/pubmed/37323925
http://dx.doi.org/10.3389/fnhum.2023.1052435
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author Higgins Tejera, César
Ware, Erin B.
Kobayashi, Lindsay C.
Fu, Mingzhou
Hicken, Margaret
Zawistowski, Matthew
Mukherjee, Bhramar
Bakulski, Kelly M.
author_facet Higgins Tejera, César
Ware, Erin B.
Kobayashi, Lindsay C.
Fu, Mingzhou
Hicken, Margaret
Zawistowski, Matthew
Mukherjee, Bhramar
Bakulski, Kelly M.
author_sort Higgins Tejera, César
collection PubMed
description BACKGROUND AND OBJECTIVES: Elevated circulating cystatin C is associated with cognitive impairment in non-Hispanic Whites, but its role in racial disparities in dementia is understudied. In a nationally representative sample of older non-Hispanic White, non-Hispanic Black, and Hispanic adults in the United States, we use mediation-interaction analysis to understand how racial disparities in the cystatin C physiological pathway may contribute to racial disparities in prevalent dementia. METHODS: In a pooled cross-sectional sample of the Health and Retirement Study (n = 9,923), we employed Poisson regression to estimate prevalence ratios and to test the relationship between elevated cystatin C (>1.24 vs. ≤1.24 mg/L) and impaired cognition, adjusted for demographics, behavioral risk factors, other biomarkers, and chronic conditions. Self-reported racialized social categories were a proxy measure for exposure to racism. We calculated additive interaction measures and conducted four-way mediation-interaction decomposition analysis to test the moderating effect of race/ethnicity and mediating effect of cystatin C on the racial disparity. RESULTS: Overall, elevated cystatin C was associated with dementia (prevalence ratio [PR] = 1.2; 95% CI: 1.0, 1.5). Among non-Hispanic Black relative to non-Hispanic White participants, the relative excess risk due to interaction was 0.7 (95% CI: −0.1, 2.4), the attributable proportion was 0.1 (95% CI: −0.2, 0.4), and the synergy index was 1.1 (95% CI: 0.8, 1.8) in a fully adjusted model. Elevated cystatin C was estimated to account for 2% (95% CI: −0, 4%) for the racial disparity in prevalent dementia, and the interaction accounted for 8% (95% CI: −5, 22%). Analyses for Hispanic relative to non-white participants suggested moderation by race/ethnicity, but not mediation. DISCUSSION: Elevated cystatin C was associated with dementia prevalence. Our mediation-interaction decomposition analysis suggested that the effect of elevated cystatin C on the racial disparity might be moderated by race/ethnicity, which indicates that the racialization process affects not only the distribution of circulating cystatin C across minoritized racial groups, but also the strength of association between the biomarker and dementia prevalence. These results provide evidence that cystatin C is associated with adverse brain health and this effect is larger than expected for individuals racialized as minorities had they been racialized and treated as non-Hispanic White.
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spelling pubmed-102673112023-06-15 Decomposing interaction and mediating effects of race/ethnicity and circulating blood levels of cystatin C on cognitive status in the United States health and retirement study Higgins Tejera, César Ware, Erin B. Kobayashi, Lindsay C. Fu, Mingzhou Hicken, Margaret Zawistowski, Matthew Mukherjee, Bhramar Bakulski, Kelly M. Front Hum Neurosci Neuroscience BACKGROUND AND OBJECTIVES: Elevated circulating cystatin C is associated with cognitive impairment in non-Hispanic Whites, but its role in racial disparities in dementia is understudied. In a nationally representative sample of older non-Hispanic White, non-Hispanic Black, and Hispanic adults in the United States, we use mediation-interaction analysis to understand how racial disparities in the cystatin C physiological pathway may contribute to racial disparities in prevalent dementia. METHODS: In a pooled cross-sectional sample of the Health and Retirement Study (n = 9,923), we employed Poisson regression to estimate prevalence ratios and to test the relationship between elevated cystatin C (>1.24 vs. ≤1.24 mg/L) and impaired cognition, adjusted for demographics, behavioral risk factors, other biomarkers, and chronic conditions. Self-reported racialized social categories were a proxy measure for exposure to racism. We calculated additive interaction measures and conducted four-way mediation-interaction decomposition analysis to test the moderating effect of race/ethnicity and mediating effect of cystatin C on the racial disparity. RESULTS: Overall, elevated cystatin C was associated with dementia (prevalence ratio [PR] = 1.2; 95% CI: 1.0, 1.5). Among non-Hispanic Black relative to non-Hispanic White participants, the relative excess risk due to interaction was 0.7 (95% CI: −0.1, 2.4), the attributable proportion was 0.1 (95% CI: −0.2, 0.4), and the synergy index was 1.1 (95% CI: 0.8, 1.8) in a fully adjusted model. Elevated cystatin C was estimated to account for 2% (95% CI: −0, 4%) for the racial disparity in prevalent dementia, and the interaction accounted for 8% (95% CI: −5, 22%). Analyses for Hispanic relative to non-white participants suggested moderation by race/ethnicity, but not mediation. DISCUSSION: Elevated cystatin C was associated with dementia prevalence. Our mediation-interaction decomposition analysis suggested that the effect of elevated cystatin C on the racial disparity might be moderated by race/ethnicity, which indicates that the racialization process affects not only the distribution of circulating cystatin C across minoritized racial groups, but also the strength of association between the biomarker and dementia prevalence. These results provide evidence that cystatin C is associated with adverse brain health and this effect is larger than expected for individuals racialized as minorities had they been racialized and treated as non-Hispanic White. Frontiers Media S.A. 2023-06-01 /pmc/articles/PMC10267311/ /pubmed/37323925 http://dx.doi.org/10.3389/fnhum.2023.1052435 Text en Copyright © 2023 Higgins Tejera, Ware, Kobayashi, Fu, Hicken, Zawistowski, Mukherjee and Bakulski. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Higgins Tejera, César
Ware, Erin B.
Kobayashi, Lindsay C.
Fu, Mingzhou
Hicken, Margaret
Zawistowski, Matthew
Mukherjee, Bhramar
Bakulski, Kelly M.
Decomposing interaction and mediating effects of race/ethnicity and circulating blood levels of cystatin C on cognitive status in the United States health and retirement study
title Decomposing interaction and mediating effects of race/ethnicity and circulating blood levels of cystatin C on cognitive status in the United States health and retirement study
title_full Decomposing interaction and mediating effects of race/ethnicity and circulating blood levels of cystatin C on cognitive status in the United States health and retirement study
title_fullStr Decomposing interaction and mediating effects of race/ethnicity and circulating blood levels of cystatin C on cognitive status in the United States health and retirement study
title_full_unstemmed Decomposing interaction and mediating effects of race/ethnicity and circulating blood levels of cystatin C on cognitive status in the United States health and retirement study
title_short Decomposing interaction and mediating effects of race/ethnicity and circulating blood levels of cystatin C on cognitive status in the United States health and retirement study
title_sort decomposing interaction and mediating effects of race/ethnicity and circulating blood levels of cystatin c on cognitive status in the united states health and retirement study
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267311/
https://www.ncbi.nlm.nih.gov/pubmed/37323925
http://dx.doi.org/10.3389/fnhum.2023.1052435
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