Browsing by Author "Nolan, Emma"
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Item Association between everyday perceived discrimination and cognitive function as mediated by depression in diverse populations: A HABS-HD Study(2024-03-21) Mendoza, Edna Patricia; Nolan, Emma; Phillips, Nicole; Barber, Robert; O'Bryant, Sid; Zhou, ZhengyangPurpose: Previous research suggests that perceived discrimination is associated with cognitive function impairment, and such association is mediated by depression. With minority populations continuously growing, it is crucial to investigate such relationships in diverse populations. This study aims to examine and compare the above relationships among non-Hispanic white (NHW), Mexican American (MA), and African American (AA) participants. Method: A sample size of 1,129 participants (640 AAs, 248 NHWs, 241 MAs) aged 50+ came from the Health and Aging Brain Study – Health Disparities (HABS-HD). Structural equation modelling (SEM) was conducted to explore the effect between perceived discrimination, measured by the Everyday Discrimination Scale mean score, and cognitive function, measured by the Mini Mental State Examination (MMSE) Score. The mediation effect of depression, measured by the Geriatric Depression Scale total score, was evaluated by the indirect effect estimate using SEM. Result: Everyday perceived discrimination negatively influenced cognitive function, and the effect was mediated by depression across the three populations (β= -0.15, 95% CI = [-0.22, -0.08]). When stratified, the mediation effect of depression on the association between discrimination and cognitive function remained significant for NHW (β= -0.37, 95% CI = [-0.60, -0.15]) and MA (β = -0.27, 95% CI = [-0.50, -0.05]). However, such mediation effect was not observed for the AA population. Conclusion: Depression mediates the link between everyday discrimination and cognitive decline, but differences between racial/ethnic groups underscore the need for further research into underlying mechanisms among minority groups, including Mexican American and African American populations. Depression interventions may mitigate negative cognitive effects from discrimination. Tailoring such interventions by race/ethnicity and targeting at-risk groups could optimally promote cognitive health.Item A mendelian randomization analysis of obesity on the development of Alzheimer’s disease(2023) Nolan, Emma; Zhou, ZhengyangPurpose: To assess the causal associations between obesity and Alzheimer’s disease (AD) using Mendelian randomization analysis based on summary statistics from genome-wide association studies (GWAS). The most recent GWAS as of November 2021 for AD and obesity were used, including newly identified risk single nucleotide polymorphisms (SNPs) that were associated with AD and obesity. Specifically, the AD GWAS identified 42 new risk loci, which have not been utilized in other studies. Thus, this study provides novel evidence for the causal associations of AD and obesity. Methods: Genetic associations for the exposure (i.e., obesity; BMI ≥ 30kg/m2) were evaluated from a GWAS conducted on European individuals over age 18 in the FinnGen project (n = 218,792). Genetic associations for AD were evaluated from the whole exome sequencing data among European individuals aged 37-73 years in the UK Biobank study (n = 111,326 AD cases and 677,633 controls). Based on the above summary statistics, a Two Sample Mendelian randomization (MR) analysis using the Inverse-Variance Weighted (IVW) method was conducted to evaluate the causal association between obesity and AD. Sensitivity analyses including median-based, mode-based, and MR-Egger MR methods were conducted to confirm findings from the main MR analysis. Results: Obesity was found to be associated with a decreased odds in the development of AD (Odds ratio = 0.91, 95% CI = [0.86, 0.95], p = 0.0001) according to the IVW method, suggesting a protective effect of obesity. The results of all sensitivity analyses were consistent with the main findings and determined the absence of horizontal pleiotropy and heterogeneity. Specifically, significant causal relationship between AD and obesity was identified in the IVW method and Weighted Median MR methods. Conclusion: The protective effect of obesity on the development of AD is supported by the MR analysis in this study. Further research should be conducted on the underlying pathological mechanism to inform potential health interventions such as weight modification in mid versus late life.