Browsing by Author "O'Bryant, Sid"
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Item Alzheimer's Disease Risk Allele Frequencies Differ Based on Ethnicity in HABLE Cohort(2022) Housini, Mohammad; Rao, Sumedha; Phillips, Nicole; O'Bryant, Sid; Barber, Robert C.Purpose: Alzheimer's Disease (AD) or other related dementias remain a significant burden on our aging population. Here we evaluate the top 10 AD risk alleles previously reported by Kunkle et al. (2018) in Mexican Americans and non-Hispanic whites enrolled in the Healthy Aging Brain in Latino Elders Study (HABLE) cohort to see if allele frequencies vary based on ethnicity. Methods: DNA was extracted from buffy coat samples (n = 1635) on the Hamilton robotic system with the Mag-Bind Blood & Tissue DNA HDQ 96 Kit. Genotyping was performed per manufacturer's protocol using the Illumina Infinium Global Screening Array (GSA) and analyzed with Genome Studio 2.0. Samples with call rates less than 98% were repeated or excluded. Allele and genotype frequencies were calculated using standard statistics by compiling the top ten AD risk alleles from Kunkle et al. (2018) and measuring their frequencies in the HABLE cohort. Results: Our data suggest varying degrees of allele and genotype frequencies among the top 10 risk conferring SNPs between Mexican Americans and Non-Hispanic Whites. In particular, we show some instances (BIN1, PTK2B) where the heterozygotes are in higher frequency than homozygotes. 8 of our evaluated SNPs show a difference greater than 5% between the two ethnicities. Conclusion: It may be beneficial to further study the top AD risk alleles among different ethnicities to determine if there are variable frequencies in those populations. We plan to expand and continue this work in other ethnicities and further elaborate on these differences to promote ethnicity targeted diagnostics and help reduce health disparities in medicine and science.Item Application of Structural Retinal Biomarkers to Detect Cognitive Impairment in a Primary Care Setting(2023) Nyalakonda, Ramyashree; Petersen, Melissa; Zhang, Fan; Johnson, Leigh; Tolman, Alex; Gutierrez, Alejandra; O'Bryant, Sid; Mozdbar, SimaIntroduction Alzheimer’s Disease (AD) is the most prevalent form of dementia and a leading cause of death in the elderly. The detection of AD remains poor in primary care despite the advancement of neurodiagnostic procedures. There are no rapid and cost-effective tools available to primary care providers to conduct cognitive examinations to diagnose AD. The goal of this study is to determine the predictive ability of structural retinal biomarkers to identify cognitive impairment in a primary care setting. Methods Participants were recruited from Alzheimer’s Disease in Primary Care (ADPC) study. As part of the ADPC Retinal Biomarker Study (ADPC RBS), visual acuity, an ocular history questionnaire, eye pressure, optical coherence tomography (OCT) imaging and fundus imaging was performed. Exclusion criteria included high intraocular pressure defines as greater than or equal to 30 mmHg in either eye, history of adverse effects with pupillary relation, known hypersensitivity to tropicamide or any ingredient in the formulation, active ocular infection or inflammation, history of angle closure glaucoma, or having undergone ocular surgery within the last 6 months. Cognitive diagnoses were assigned algorithmically and verified at consensus review by an expert in the field of dementia. Results Data were examined on a total of 91 participants (59 cognitively unimpaired, 32 cognitively impaired (26 mild cognitive impairment (MCI), 6 AD)). The top biomarkers for predicting cognitive impairment included the inferior quadrant of the outer retinal layers, all four quadrants of the peripapillary retinal nerve fiber layer (pRNFL), and the inferior quadrant of the macular retinal nerve fiber layer. While all four quadrants of the pRNFL are highly important biomarkers for identifying those with cognitive impairment, the inferior and superior quadrants displayed higher relative importance compared to the temporal and nasal quadrants. Conclusion This study was the first to examine the utility of retinal biomarkers in diagnosis cognitive impairment in a primary care setting with models reflecting how it could be employed as a screening tool in practice. The current data provides strong support for continued investigation into structural retinal biomarkers, particularly the retinal nerve fiber layer, as screening tools for AD. In prior studies, preferential thinning of the inner retinal layers is found in AD compared to healthy controls. This study can help distinguish those with cognitive impairment from those cognitively unimpaired. The availability of such a biomarker could increase access to disease modifying treatments once available.Item Area deprivation index and cognitive function: A cross-sectional study of the HABS-HD cohort(2023) Benton, Abigail; Vintimilla, Raul; Hall, James; Johnson, Leigh; O'Bryant, SidPurpose: Dementia is an ever-growing group of disorders worldwide. It is proposed that neighborhood socioeconomic status (NSES) is linked with overall health, and this study will evaluate whether NSES is cross-sectionally associated with cognition in non-Hispanic White, African American, and Mexican American participants of the Health and Aging Brain: Health Disparities Study (HABS-HD). Methods: The HABS-HD is a longitudinal study conducted by the Institute for Translational Research at the University of North Texas Health Science Center. Participants (n=1634) were age 50 years or older, and underwent a clinical interview, neuropsychological exam battery, functional examination, head MRI, amyloid PET scan, and blood draw for clinical and biomarker analysis. NSES was measured using the national area deprivation index (ADI) percentile ranking, which considered the variables of education, employment, income, occupation, and housing. Cognition was assessed by the Mini-Mental State Examination, Trails B Exam, FAS Test, Spanish English Verbal Learning Test, and Digit-Symbol Substitution Test. The cognitive performance in those living in the 20% most disadvantaged neighborhoods was compared to those in the 80% least disadvantaged neighborhoods using multiple linear regression models with age, sex, education, and ethnicity as control variables. Results: Those in the most deprived neighborhood group were statistically significantly (p<0.05) younger, less educated, more likely to be female, and more likely to be Mexican American. The means of MMSE and Trails B test were lower in those living in the more deprived neighborhood group (p<0.05). When looking at the linear model of ADI and cognition, after adjusting for covariates, only Trails B scores were related to the higher deprived neighborhood group (t = -0.62, p <0.0001). Conclusion: Our study revealed that some measures of cognitive impairment were higher in people living in the top 20% disadvantaged neighborhoods. In future studies, specific markers of deprivation should be analyzed along with cognitive impairment to more specifically advocate for beneficial change. Further, due to sex and ethnicity being significant cofounders, analysis should be run by ethnicity to investigate this distinction.Item Association Between bilingualism and Amyloid Uptake Among Mexican Americans: An HABS-HD Study(2022) Wiley, Elizabeth; Johnson, Leigh; Hall, James; Petersen, Melissa; O'Bryant, SidBackground: Bilingualism is thought to provide protective benefits in regions of the brain associated with the onset of Alzheimer's Disease (AD). While there has been extensive research on bilingualism's effect on grey matter volume, there is no study to date that has examined the relationship between bilingualism and amyloid burden within brain regions characteristically impacted by AD. This study aims to fill this gap by comparing amyloid deposition in Mexican Americans who are either monolingual or bilingual. Methods: Data were analyzed on n=34 Hispanic, Mexican Americans (n=16 bilingual; n=18 monolingual) participants enrolled in a study of health disparities with available Amyloid PET scans. PET Amyloid scans were conducted using florbetaben (18F) on a Siemens Biograph Vision 450 whole-body PET/CT scanner. PET Amyloid SUVR levels were generated from the following Regions of Interest (ROIs): Frontal, Anterior Posterior Cingulate, Lateral Parietal, Lateral Temporal, and Global, with global SUVR>1.08 determined as the cut-off for Amyloid positivity. Independent t-test and chi-square tests were conducted to examine group differences in language status across demographic variables. One-way ANOVAs were conducted to examine groups differences in APOE e4 carrier status as well as in language capabilities (monolingual, bilingual) and PET amyloid SUVR. Follow-up analyses examining language capabilities were split by APOE e4 carrier status (carrier, non-carrier). Results: In comparison to APOE e4 non-carriers, APOE e4 carriers experienced significantly increased amyloid burden across all regional areas, including global (p< 0.05). Bilingual APOE e4 non-carriers showed a significantly increased amyloid deposition in the Anterior/Posterior Cingulate cortex in comparison to monolingual APOE e4 non-carriers. Furthermore, among APOE e4 non-carriers, there was a trend towards significance for global amyloid uptake (p=0.059), with bilinguals again showing higher amyloid burden. Among APOE e4 carriers, no significant associations were found between language status (monolingual, bilingual) and amyloid uptake. Discussion: This was the first study to examine the association between bilingualism and amyloid burden within specific cortical regions of the brain. Results contradicted previous work observing the role of the posterior/anterior cingulate in bilingualism. The trend towards significance in global amyloid uptake for APOE e4 non-carriers favored increased burden in bilinguals, a result opposite of what was expected. Bilingualism is complex and multifactorial and further work is greatly needed to understand the link it has with amyloid burden particularly by disease state.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 Association between inflammation, white matter hyperintensities, and executive function: the role of ethnicity.(2022) Brown, Frank; Vintimilla, Raul; Hall, James; Johnson, Leigh; O'Bryant, SidAssociation between inflammation, white matter hyperintensities, and executive function: the role of ethnicity. Frank Brown1, Raul Vintimilla2, James Hall2, Leigh Johnson2, Sid O'Bryant2, for the HABS-HD Study Team. 1University of North Texas 2University of North Texas Health Science Center, Institute for Translational Research Background: Systemic inflammation and cardiovascular risk factors (CVRF) impact neurological health and executive function. Neutrophils produce inflammatory mediators and lymphocytes regulate the inflammatory response. Neutrophil to lymphocyte ratio (NLR) has been used as a marker of systemic inflammation, and as a predictor of cardiovascular health. CVRF are correlated with white matter hyperintensity volume (WMH), an MRI indicator of cerebrovascular health. This study seeks to compare if there is a difference in the association between inflammation (NLR), WMH, and executive function among Mexican Americans and non-Hispanic Whites. Method: We analyzed data from 1083 (505 Mexican Americans and 578 non -Hispanic Whites) cognitively normal participants from the Health and Aging Brain Study (HABS-HD). All participants signed a written consent, and underwent a 3T MRI (Siemens Skyra), clinical labs, clinical evaluation, and cognitive testing. Differential blood cell counts were used to obtain NLR. WMH volume was measured from FLAIR using the Statistical Parametric Mapping (SPM) Lesion Segmentation Tool. Linear regression was used to predict the effect of NLR and Log transformed WMH adjusted for intracranial volume (derived from Freesurferv6.0 analysis of T1 MPRAGE) on Trails B z-score (executive function), and to evaluate if NLR can predict WMH volume. Analysis was split by ethnicity. Age, sex, and education were entered as covariates in the models. Results: Sixty-four percent of the total sample were female. Means for the whole sample were: age 66.02, education years 12.98, Trails B 0.19, WMH volume -0.035, and NLR 2.16. When compared to non-Hispanic Whites, Mexican Americans were significantly younger, less educated, had lower Trails B score, NLR values and WMH volume. NLR predicted Trails B scores (B = -0.14, t =-0.12, p = 0.004) only in Mexican American, while WMH predicted Trails B scores in Mexican American (B = -0.16, t = -3.02, p = 0.003), and Non-Hispanic Whites (B = -0.14, t = -4.33, p < 0.0001). Results remained significant after adjusting for age, sex, education. NLR predicted WMH volume (B = 0.13, t = 3.38, p = 0.001) only in Mexican American. Conclusion: Our findings suggest an association between NLR, WMH and executive function in Mexican Americans. NLR and WMH volume predicted Trails B scores in Mexican Americans. WMH predicted Trails B scores, but there was no association between NLR and executive function in non-Hispanic Whites. These findings demonstrate the importance of race consideration when assessing the relationship between inflammation, CVRF, WMH, and executive function.Item Association of Area Deprivation Index and hypertension, diabetes, dyslipidemia, and obesity: a cross-sectional study of the HABS-HD cohort.(2023) Seyedahmadi, Armin; Vintimilla, Raul; Hall, James; Johnson, Leigh; O'Bryant, SidBackground: Heart disease is a leading cause of death globally and the prevalence of cardiovascular disease (CVD) is expected to increase significantly in the United States over the next decade. Previous research has shown that socioeconomic status has a significant impact on CVD prevalence and outcomes, with risk factors for CVD being more prevalent in individuals from low socioeconomic groups. We aimed to investigate the association between neighborhood deprivation and the prevalence of major CVD risk factors (hypertension, diabetes, dyslipidemia, and obesity) in a Mexican American population compared to Non-Hispanic Whites. Methods: A cross-sectional analysis was conducted to include 1867 subjects. 971 self-identified as Mexican American (MA), and 896 as Non-Hispanic White (NHW). These participants underwent a clinical interview, neuropsychological exam battery, functional examination, MRI of the head, amyloid PET scan, and blood draw for clinical and biomarker analysis. They were also assigned an ADI score based on participants living in the best and worst neighborhoods according to Area Depravation Index (ADI) model. Results: Sixty percent of the sample was female. MA were significantly younger (mean age 63.37 vs 68.64) and less educated (mean education years 9.69 vs 15.61 than NHW. Additionally, MA had a significantly higher prevalence of HTN, DM, and obesity. Only 12.3% of Non-Hispanic Whites lived in the most deprived neighborhoods (percentile 4), while 57.5% of Mexican Americans lived in the percentile 4 ranking areas (p≤ .05). There was a significant difference between non-Hispanic White participants living in the least deprived neighborhoods compared to participants living in the most deprived neighborhoods for HTN (OR = 2.14, 95% CI [1.31, 3.48]), DM (OR = 3.42; 95% CI [1.67, 7.01]), and obesity (OR = 3.03, 95% CI [1.86 to 4.95]). There was no significant difference in the odds of having dyslipidemia between non-Hispanic Whites living in the ADI quartile 1 when compared to those living in the ADI quartile 4. These results remained significant after adjusting for age, sex, education, and cardiovascular risk factors. Conclusion: In conclusion, this study found the area deprivation index (ADI) is associated with cardiovascular risk factors such as hypertension, diabetes, dyslipidemia, and obesity. These findings suggest that socioeconomic status may play a role in the prevalence of certain health conditions among different ethnic groups. Further research is needed to understand the underlying mechanisms and to develop interventions that address health disparities among different ethnic populations.Item Carotid arterial stiffness and cerebral blood flow variability in individuals with mild cognitive impairment(2023) Bhuiyan, Nasrul; Davis, K. Austin; Vintimilla, Raul; Borzage, Matthew; Pahlevan, Niema; King, Kevin; Johnson, Leigh; O'Bryant, Sid; Rickards, CarolinePurpose: It is unclear whether cerebral blood flow variability is a sign of impaired vascular function or an adaptation to chronic cerebral hypoperfusion in individuals with cognitive dysfunction. Elevated arterial stiffness increases transmission of pulsatile pressure to the brain, but the relationship between arterial stiffness, the magnitude of cerebral blood flow variability, and cognitive dysfunction is unknown. In this pilot study, we hypothesized that carotid artery stiffness would be higher in individuals with mild cognitive impairment (MCI) compared with individuals with normal cognition (NC), resulting in higher cerebral blood flow variability. Methods: In individuals with MCI (N=5) or NC (N=7), R-wave to common carotid artery (CCA) pulse wave velocity (PWV) was assessed as an index of arterial stiffness (via tonometry). CCA velocity (CCAv) and middle cerebral artery velocity (MCAv) were measured via transcranial Doppler ultrasound, with concurrent measurements of mean arterial pressure (MAP) via finger photoplethysmography. The amplitude of MAP, CCAv, and MCAv oscillations in the low frequency range (LF; 0.07-0.15 Hz) were assessed via fast Fourier transformation, and normalized to total power (0.04-0.4 Hz) for each participant to account for high inter-individual variability. Relationships between R-wave-carotid PWV and LF variability in CCAv and MCAv were assessed via correlational analyses. Results: There were no between-group differences for R-wave-carotid PWV (MCI: 0.91±0.16 m/s vs. NC: 0.87±0.07 m/s; P=0.70), mean CCAv (MCI: 31.8±8.8 cm/s vs. NC: 29.7±2.0 cm/s; P=0.54), mean MCAv (MCI: 50.9±6.5 cm/s vs. NC: 47.9±12.7 cm/s; P=0.63), or MAP (MCI: 102.1±10.2 mmHg vs. 104.7±13.8 mmHg; P=0.73). While there was also no difference between groups for nLF power of CCAv (MCI: 0.28±0.03 au vs. NC: 0.33±0.10 au; P=0.41), nLF power for MCAv was lower in the MCI group (MCI: 0.26±0.07 au vs. 0.43±0.12; P=0.02). Overall, there was a strong positive correlation between R-wave-carotid PWV and CCAv nLF power (R=0.81, P=0.005), but a weaker relationship for MCAv nLF power (R=0.56, P=0.09). While sub-group correlational analyses are limited based on the small sample sizes, relationships between R-wave-carotid PWV and CCAv nLF power were high for both MCI (R=0.98, P=0.02) and NC (R=0.79, P=0.06) groups, but were lower for MCAv nLF power (MCI: R=-0.12, P=0.88; NC: R=0.69, P=0.13). Conclusion: Contrary to our hypothesis, there were no differences in R-wave-carotid PWV between groups, and blood flow variability was either similar between groups (for CCAv), or lower in the MCI group (for MCAv). Overall, there was a strong positive relationship between R-wave-carotid PWV and blood flow variability in the CCA, which was also observed in sub-analysis of the MCI and NC groups. Future investigations with a larger sample size are needed to definitively determine the role of arterial stiffness on cerebral blood flow variability with cognitive dysfunction.Item Comparing Framingham Cardiovascular Disease Risk Score and Cognitive Performance between Cognitive Normal Non-Hispanic Whites and Mexican American Elders(2020) O'Bryant, Sid; Johnson, Leigh; Vintimilla, Raul; Hall, James; Balasubramanian, KishorePurpose: To compare the relationship between Framingham Risk Scores and cognitive function between a cohort of Mexican-Americans (MAs) and Non-Hispanic Whites (NHWs). Methods: 518 cognitively normal participants (92 NHWs and 426 MAs) from the Health and Aging Brain Among Latino Elders study were studied. Demographic and clinical data relevant to Framingham Cardiovascular Disease 10-year Risk Score (FCVDRS) were assessed. FCVDRS was calculated based on BMI and categorized as Low if < 10, Moderate if between 10-20, and High if >20. Cognitive performance was evaluated using Trails B, Wechsler Logical Memory I and II, Mini Mental State Examination (MMSE), and Animal Naming (AN) tests. Demographic data was analyzed using t-tests and chi-square tests as appropriate. Pearson correlation tests and ANOVAs were used in comparing FCVDRS and FCVDRS categories against cognitive performance respectively. Results: MAs had significantly higher BMI, Systolic BP, and prevalence of Diabetes. Significantly higher proportion of NHWs were current smokers and were undergoing Hypertension treatment. Both cohorts were primarily female and had no significant difference in FCVDRS. Pearson Correlation Tests and ANOVAs were significant for Trails B, MMSE, and AN in MAs only. Tukey post-hoc tests showed significantly decreased performance for High-Risk groups when compared to Low-Risk groups in Trails B and when compared to Moderate-Risk risk groups in MMSE and AN. Conclusion: Mexican-Americans with High FCVDRS show decreased cognitive performance when compared to NHWs. FCVDRS could be used to identify high risk Mexican-Americans for early intervention.Item Comparison of support vector machine, random forest, extreme gradient boosting and lasso and elastic-net regularized generalized linear model for Alzheimer's Disease prediction(2021) Zhang, Fan; Petersen, Melissa; Johnson, Leigh; Hall, James; O'Bryant, SidPurpose: Machine learning based blood test shows promise in detecting Alzheimer's disease (AD) and pinpointing mechanisms underlying the process of neurodegeneration. Model selection plays a crucial role in building good machine learning models for AD prediction. Methods: The paper presents a comparison of four machine learning algorithms: support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost )and lasso and elastic-net regularized generalized linear model (GLMNET) for Alzheimer's disease prediction using blood test data from serum. First, we implemented 10 times repeated 5-fold cross-validation to split the data into training set and testing set randomly 50 times to select the best hyperparameters for each selected machine learning method. Then we selected the best learning model based on the performance metrics in the testing set. Results: Of all compared prediction results in the training set, RF and XGBoost achieved the highest negative predictive value (100%) followed by SVM with 99.40% and GLMNET with 94.45%. Of all compared prediction results in the testing set, SVM achieved the highest negative predictive value (96.96%) followed by XGBoost with 95.94%, RF with 95.59%, and GLMNET with 94.27%. With 28-cores high performance computing, RF took 1.35 hours CPU usage, SVM 1.10 hours, XGBoost 48 seconds, and GLMNET 47 seconds, respectively. Conclusions: SVM, RF, and XGBoost are the top three best models for AD prediction. SVM performs better in handling overfitting problem in the training set with small size than RF and XGBoost and also achieved best performance in the testing set.Item Determining the Viability of Biomarkers for Oxidative Stress Detection in Clinically Afflicted Cohorts(2015-03) Duong, Phong; Contreras, Jo G.; Snyder, Brina; O'Bryant, Sid; Cunningham, RebeccaIntro: In the US, there are more than 5 million Americans living with Alzheimer’s disease (AD) and approximately 500,000 more are suffering from Parkinson’s disease (PD). Oxidative stress (OS) and its deregulation of reactive oxygen species (ROS) have been implicated as a component of neurodegenerative diseases. Accumulation of ROS is accountable for increasing mitochondrial dysfunction that leads to neuronal apoptosis. In addition to ROS accumulation, OS can result in a number of cellular by-products such as Malondialdehyde (MDA), 8-Isoprostane, and Advanced Oxidation Protein Products (AOPP). Recent studies also suggest that high levels of testosterone can depress cellular resistance to oxidative stress. Purpose: The objective of this research is to determine the viability of laboratory assays as a detection tool for the evaluation of neurodegenerative diseases in aging males. Methods: 352 clinical plasma samples from the Texas Alzheimer’s Research and Care Consortium were used in assay evaluation. The samples were collected from either Caucasian or Hispanic males and evaluated based on 6 previously determined disease statuses. The AOPP Assay was used to detect chlorinated oxidation of plasma proteins. For AOPP, plasma samples were performed with a 1:7 dilution factor. Following preparation, the samples were then plated in duplicates and read at an absorbance of 340nm. To correlate with a previous testosterone study, a Testosterone ELISA was conducted with the use of Rabbit Anti-Free T-Antibody without sample dilution. Once plated, the samples were incubated for 60 minutes, washed, and read at an absorbance of 450nm. MDA can be accounted for in OS-resultant lipid peroxidation (LP). MDA levels in the clinical samples were examined using a Colorimetric TBARS Assay. The assay subjected the samples to boiling, centrifuging, and incubation in an ice bath. The supernatant was then removed, plated, and read at an absorbance of 532nm. Results: The absorbance reading from the AOPP assay and Colorimetric TBARS assay, yielded similar results across all six-disease statuses. Despite the differences in disease status, samples were determined to have triple the amount of MDA concentration compared the control. Conclusion: The similarity in values and discrepancy from the control indicates that AOPP and TBARS cannot accurately determine OS in banked plasma samples. T-ELISA is currently undergoing further scrutiny with the use of mass spectrometry.Item The Differential Effects of Type II Diabetes Between Ethnicities: A Descriptive Study Comparing Hispanics, African American, and Non-Hispanic White Older Adults with Type II Diabetes(2024-03-21) Sharma, Monish; Large, Stephanie; O'Bryant, SidAbstract Purpose: Type II diabetes mellitus (T2DM) is a significant risk factor for cognitive impairment. Individuals with T2DM have an increased risk for developing depression and depressive episodes. Additionally, T2DM worsens other comorbid conditions such as hypertension and high cholesterol. To gain a better understanding of the etiology and risk factors for the complications of T2DM, it is important to assess how T2DM impacts different ethnic groups. This study aims to explore how T2DM effects Hispanics (H), Non-Hispanic Whites (NHW), and African American (AA) older adults regarding self-reported health and past medical history, objective measures, and clinical blood work. Methods: Data was collected from 767 (187 AA, 161 NHW, 419 H) participants with T2DM from the Health and Aging Brain Study: Health Disparities, baseline studies. T2DM was defined as an HbA1C of greater than or equal to 6.5 or by self-report. The participants had an average age of 65 years. One-way ANOVAS were run to examine group differences in demographics, physical activity (RAPA), affect (Geriatric Depression Scale: depression; Penn State Worry Questionnaire: worry), blood pressure, and clinical blood work. Results: ANOVAs demonstrated significant differences in education between H (M = 8.84, SD = 4.51), NHW (M = 15.32, SD = 2.62), AA (M = 14.57, SD = 2.66) groups (F = 246.74, p <0.001). Significant differences in income were also recorded between H (M= 30,530.31, SD = 28,055.79), NHW (M =65,265.45, SD = 53,241.75), AA (M = 61,423.46, SD = 69,393.76) groups (F = 44.63, p < 0.001). Clinically, significant differences in systolic blood pressure were found between H (M = 140.83, SD = 20.98), NHW (M = 137.58, SD = 18.69), AA (M = 136.44, SD = 20.56) groups (F = 3.52, p = 0.03). The cholesterols (total cholesterol, HDL, triglycerides, LDL, HDL ratios, and non-HDL) were all statistically significant between groups (F range 3.35 – 21.13, p range <0.001 – 0.036). ANOVAs also highlighted significant differences in physical activity (RAPA) between H (M = 3.84, SD = 1.49), NHW (M = 4.18, SD = 1.52), AA (M = 4.18, SD = 1.62) groups (F = 4.61, p = 0.01). Lastly, significant differences in affect (GDS) were found between H (M = 7.73, SD = 6.72), NHW (M = 5.84, SD = 6.02), AA (M = 6.81, SD = 5.76) groups (F = 5.42, p = 0.01). Conclusion: This study demonstrates that Hispanic older adults with T2DM exhibit a greater decline in overall health and wellness compared to their AA and NHW counterparts. Future research should compare type II diabetic Hispanics with non-diabetic Hispanics to determine if Hispanics are already at a baseline risk for potential health complications.Item Effects of Diabetes and White Matter Hyperintensities on Cognition in Mexican Americans Based on APOE e4 Carrier Status: An HABS-HD Study(2022) Mai, Kevin; Petersen, Melissa; Hall, James; Johnson, Leigh; O'Bryant, SidBackground: The U.S. Hispanic population is projected to grow tremendously and face considerable increases in age-related conditions such as Alzheimer's Disease (AD). This same population also experiences a higher frequency of cerebrovascular conditions and diabetic risk factors, both of which have independently been associated with cognitive decline. Previous research demonstrates the impact of Diabetes Mellitus (DM) and white matter hyperintensities (WMHs) on cognitive functioning within the Hispanic population; however, to date, no study has looked into the effects of genetic factors such as APOE-e4 carrier status on the link between these medical conditions and cognition. Methods: Data were analyzed on Mexican American participants from a study of health disparities stratified by DM status (Yes/No) and WMH burden (Low/High): n = 696 APOE e4 non-carriers (n= 206 No DM/Low WMH, n= 73 Yes DM/Low WMH, n= 153 No DM/High WMH, n= 128 Yes DM/High WMH) and n = 157 APOE e4 carriers (n= 48 No DM/Low WMH, n= 17 Yes DM/Low WMH, n= 35 No DM/High WMH, n= 26 Yes DM/High WMH). All participants underwent cognitive testing and a medical exam. Neuropsychological test battery included Trail Making Test Part A and B, WMS-III Digit Span, Mini Mental Status Examination, Spanish and English Verbal Learning Test (Immediate and Delayed Recall), and Digit Symbol Substitution. Diagnosis of DM was categorized as "Yes/No" through past medical history and HbA1c blood work > 6.5. WMH status was based on a median value of 0.816 to separate "Low/High" burden. Genetic testing was completed for APOE e4 to determine carrier status. ANOVAs were conducted stratified by APOEe4 carrier status with medical condition group (Yes/No DM and Low/High WMH) entered as the predictor variable and cognitive test scores as the outcome variable. Tukey post-hoc tests were performed. Results: For APOE e4 non-carriers, participants in the Yes DM/Low WMH, No DM/High WMH, and Yes DM/High WMH groups performed worse than the No DM/Low WMH group on measures of attention, executive functioning, and processing speed. Those in the No DM/High WMH and Yes DM/High WMH groups also performed worse than the No DM/Low WMH group on measures of learning and memory. Among APOE e4 carriers, participants in the Yes DM/High WMH group performed worse than the Low DM/Low WMH group on measures of executive functioning, processing speed, immediate and delayed memory. Also, those in the Yes DM/High WMH group performed worse than the Yes DM/ Low WMH group on measures of global cognition, processing speed and delayed memory. Those in the No DM/ High WMH group performed worse than the No DM/Low WMH group in both immediate and delayed memory. Discussion: In APOE e4 carriers and non-carriers, DM and WMH burden were differentially associated with decreased test performance across multiple cognitive domains. This study tests the combined effect of DM and WMH on cognition in the context of APOE carrier status for Mexican Americans with findings that support the presence of specific associations thereby further highlighting the necessity to explore health disparities.Item Epigenetic Risk Factors for Mild Cognitive Impairment, Alzheimer’s Disease and Metabolic Dysfunction in Mexican Americans(2018-03-14) Silzer, Talisa; Sun, Jie; Phillips, Nicole; Johnson, Leigh; O'Bryant, Sid; Barber, Robert C.; Abraham Daniel, AnnPurpose: Alzheimer’s is the most common form of dementia and the 5th leading cause of death for those over 651. The population of Mexican American elders will grow seven-fold by 20502 with rates of mild cognitive decline (MCI) and Alzheimer’s disease (AD) increasing exponentially1. Mexican Americans are diagnosed with MCI and AD at younger ages than non-Hispanic whites3; 4. In addition, Mexican Americans who are diagnosed with AD are 1) less likely to carry the ApoEε4 genotype3-5., 2) suffer a greater burden of type 2 diabetes3; 6, 3) experience greater metabolic-related cognitive decline7; 8 and 4) display a proteomic signature of AD that is heavily metabolic in nature4; 9, compared to non-Hispanic whites, whose proteomic signature for AD is dominated by inflammatory proteins. We hypothesized that differentially methylated regions of DNA (DMRs) are associated with age at onset of cognitive decline (MCI/AD) and metabolic dysfunction (metabolic syndrome/type 2 diabetes) in Mexican Americans. Methods: To test this hypothesis, we assayed genomic DNA methylation in samples from 14 female Mexican American participants enrolled in the Health and Aging Brain study in Latino Elders (HABLE). Participants were diagnosed with cognitive decline (n=4), metabolic dysfunction (n=3), both (n=4), or as a control (n=3). We isolated DNA from leukocytes and bisulfite treated the samples before running them on an Illumina MethylationEPIC chip in accordance with manufacturer’s recommendations to assay genomic DNA methylation. Results: Several interesting biological pathways showed significantly different methylation status between groups. When the participants were split on cognitive decline, DNA in the amyloid secretase, EGF receptor signaling, PDGF signaling, gonadotropin-releasing hormone receptor and Wnt signaling pathways were significantly hypermethylated in cases. In comparison, analyses based on metabolic dysfunction showed significant DNA hypomethylation in the beta1 and beta2 adrenergic receptor signaling pathways and hypomethylation of the gonadotropin releasing hormone receptor pathway in cases. Conclusions: The etiology of cognitive decline appears to differ between Mexican Americans and non-Hispanic whites. Future work will resolve how dementia risk differs between these and other ethnic groups. The knowledge gained from these studies will be critical to a better understanding of AD pathophysiology and the development of ethnicity-focused AD treatment options. Acknowledgements: Research reported here was supported by the National Institute On Aging of the National Institutes of Health under Award Number R01AG054073. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The research team also thanks the local Fort Worth community and participants of the Health & Aging Brain Study.Item Impact of Hypertension, Diabetes, and Dyslipidemia Comorbidity on Cognition among Hispanic Mexican Americans: An HABLE Study(2015-03) Borden, Ashley N.; Johnson, Leigh; Edwards, Melissa; O'Bryant, SidBackground: Hypertension, hyperlipidemia, and diabetes mellitus are medical diagnoses that occur at high prevalence rates among the Hispanic Mexican American population. Current research shows that each individual diagnosis is linked to cognitive decline, but this assertion is limited in that these studies have been conducted on Non-Hispanic White populations only. Additionally, an insignificant number of studies have investigated the comorbidity of these diagnoses, and how that may impact risk for cognitive impairment. This study seeks to fill this gap in the literature by determining the association between combinations of these diagnoses and cognitive functioning within a Hispanic Mexican-American population. Methods: Data were analyzed from 537 Mexican American participants who met diagnostic criteria for hypertension, dyslipidemia, and diabetes mellitus (Group 1, one diagnosis, n= 148; Group 2, two diagnoses, n=219; Group 3, three diagnoses, n=170) from the Health and Aging Brain study among Latino Elders (HABLE). Information from each participant was obtained via clinical interview (including medical history, current medications, and health behaviors), informant interview, neuropsychological testing, blood draw, and physical examination. Consensus reviews were conducted weekly to review subject data, and to establish cognitive and medical diagnoses according to national guidelines. Linear regressions analyses were utilized to examine cognitive functioning, measured through the domains of memory and verbal fluency as the dependent variable, with the independent variable consisting of the number of medical diagnoses (one, two, or three). Covariates included age, gender, and education. Results: Those in Group 1 displayed poorer performance on measures of immediate (B[SE]= -2.66[1.05], t-test = -2.52, p-value=0.012) and delayed (B[SE]= -1.59[0.77], t-test= -2.04, p-value= 0.041) memory. Differentially, those in Group 2 showed poorer performance on tasks related to verbal fluency (B[SE]=-2.33[0.80], t-test= -2.88, p-value=0.004) and working memory (B[SE]=-0.59[0.24], t-test=-2.42, p-value=0.016). Group 3, which encompassed all three medical diagnoses, was not significantly related to any of the cognitive domains that were examined. Conclusion: These findings suggest that within the Hispanic Mexican American population, domains of cognitive functioning are differentially affected within each group, with Group 3 showing no significant increased risk for cognitive dysfunction. These findings do not support current research, which suggests a higher and more invariable prevalence of cognitive decline, regardless of the comorbidity of these diagnoses. Additional research is needed to investigate the neurological effects of the biological pathways associated with the varying combination of diseases, which may explain the dissimilarity in associated cognitive function.Item Membrane androgen receptor-induced oxidative stress: mechanism involved in neurodegeneration(2019-05) Tenkorang, Mavis A. A.; Cunningham, Rebecca L.; O'Bryant, Sid; Schreihofer, Derek; Barber, Robert C.Oxidative stress-associated neurodegenerative diseases, such as Parkinson's disease (PD), affect millions of people worldwide. Although aging is the greatest risk factor for PD, other significant factors may be implicated, such as sex hormones that can mediate sex differences. Men have a higher incidence and prevalence of PD than women. Therefore, testosterone, a primary male sex hormone and a known oxidative stressor, is implicated in PD pathophysiology. Since androgens can have negative effects on dopaminergic cells, it is imperative to understand the underlying mechanisms in order to determine what mediates the observed sex differences in PD prevalence. NADPH Oxidase 1 and 2 are major oxidative stress generators in the brain, thus potential targets for testosterone-induced oxidative stress and cell death. This dissertation project therefore investigates the role of androgens and membrane androgen receptor activation on NOX1/2. We hypothesize that in dopaminergic cells, testosterone activates the membrane androgen receptor (AR45) that is complexed with NOX1/2 to increase oxidative stress. In an oxidative stress environment, androgen activation of this AR45-NOX complex leads to cell death. Results indicate that classical androgen receptor (AR) antagonists do not block testosterone's negative actions in an oxidative stress environment. The effects of AR45-NOX complex on cell viability can be blocked by either degrading AR45 protein or blocking NOX activation by apocynin. Further, these results show that testosterone's detrimental effect on cells is via a non-genomic mechanism, specifically via a novel membrane androgen receptor, AR45. The findings of this study help identify key players in testosterone-induced neurodegeneration, which could serve as potential therapeutic targets for PD. Ultimately, this project provides novel mechanisms to explain thought provoking questions on male sex bias in PD.Item Polypharmacy and self-reported health status of older adults with multimorbidities in a rural community(2020) Johnson, Leigh; Rasu, Rafia; O'Bryant, Sid; Shrestha, NisthaPURPOSE: About four in ten elderly Americans suffer from multiple chronic conditions, and 39% are taking more than five medications. Polypharmacy(using ≥five medications) is associated with age, multi-morbidities, and poor self-perceived health status. Psychological and socio-educative factors influence polypharmacy and medication adherence, with limited studies in rural elders. Hence this study aims to examine the self-reported health status among older adults with multi-morbidities in rural areas. METHODS: Project FRONTIER(Facing Rural Obstacles to Healthcare Now Through Intervention, Education & Research) is a prospective epidemiological study, using community-based participatory research(CBPR) approach to study factors affecting health in Cochran, Bailey, and Parmer County. All county residents over 40 years and were eligible for inclusion in the study after informed consent. The association between medical history and health-status was examined using logistic regression. Polypharmacy and multi-morbidities were used to predict poor health status. RESULTS: About 689 individuals participated in FRONTIER with a mean age of 68, with 43% Hispanic, and 68.7% female participants. Individuals taking ≥five medications presented 2.69 times higher odds of reporting poor health-status(AOR=2.69,CI=1.85-3.90) compared to those using < 5 medications, after controlling for demographic covariates. Individuals with ≥five co-morbidities presented 4.31 times higher odds of reporting poor health-status(AOR=4.31,CI=2.67-6.95). CONCLUSION: The presence of polypharmacy and multi-morbidities increase the odds of poor self-perceived health status. Future research should examine factors that contribute to polypharmacy among rural elders, as well as the role of patient perspectives and healthcare barriers on medication usage.Item Proteomic Profiles of Tau Positivity among an Ethnically Diverse Cohort: An HABS-HD Study(2023) Do, Tony; Petersen, Melissa; Zhang, Fan; Hall, James; O'Bryant, SidPurpose: PET tau has been well documented to precede Alzheimer’s Disease (AD) and mild cognitive impairment (MCI). In the pursuit of increasing the accessibility of AD diagnosis, studies have shown that blood biomarkers including ptau181 trend with PET tau in Non-Hispanic Whites (NHW). Current literature shows limited studies on Mexican Americans (MA) who have a higher risk of AD at earlier ages. MA populations have shown to have significantly higher burden of blood biomarkers/metabolic markers that are associated with MCI including ptau181, insulin, and glucagon, but lower in plasma amyloid. Our aim is to look at the utility of AT(N) (amyloid, tau, neurodegeneration) biomarkers in the detection of PET Tau positivity status among MA and NHWs Methods: Data were analyzed from n=401 participants (Total sample [n=21 Tau positive, n=380 Tau negative]; Black [n=11 Tau positive, n=216 Tau negative]; Hispanic [n=5 Tau positive, n=50 Tau negative]; Non-Hispanic whites [n=5 Tau positive, n=114 Tau negative]) from a community-based study of brain aging the Health and Aging Brain Study- Health Disparities (HABS-HD). HABS-HD participants underwent a clinical interview, neuropsychological testing, blood draw, functional medical exam and neuroimaging as a part of the study’s protocol. Plasma blood biomarkers used in this study consisted of Amyloid Beta 40, 42, Total Tau, Ptau181 and NFL derived using Single Molecule Array Technology (SIMOA) on an HDX platform. PET Tau positivity status was determined based on a clinical read. Support Vector Machine (SVM) models were used with plasma ATN biomarkers as predictors of PET Tau positivity status (Positive; Negative). SVM models were run with 10 times, five-fold repeated cross--validation and included models with and without demographics. Results: In the total sample, ATN biomarkers produced an area under the curve (AUC) of 98% with a sensitivity [SN] of 100% and Specificity [SP] of 73% for distinguishing PET Tau Positive cases from PET Tau Negative. The same ATN biomarkers produced for Black participants an AUC of 98% (SN=100%, SP=80%), for Hispanic participants an AUC of 100% (SN=100%, SP=100%), and for Non-Hispanic White participants an AUC of 98% (SN=100%, SP=70%). The addition of demographic variables of age, gender, and education produced a slight increase in the AUC for both black and non-Hispanic white participants by 1%. The top biomarkers were shown to vary by race and ethnic group. Conclusions: The results further support the AT(N) biomarkers as a viable method in predicting AD/PET tau positivity, as well as confirming that ptau181 has heavy influence in MA. The varying results of top biomarkers between groups confirm that ethnic background plays a strong role in biomarker profiles contributing to AD. An interesting finding was that demographic factors were ranked higher in black participants in distinguishing PET Tau positivity as compared to NHW and MA. Future work should expand on ptau181 value in relation to MCI state/AD progression in MA.Item Quality of life in Medicaid patients 50 and over(2015-03) Large, Stephanie; Mathew, Susan; Richardson, Janice; Gamboa, Adriana; Vintimilla, Raul; Connally, Patrica; O'Jile, Judith R.; Johnson, Leigh; O'Bryant, SidIntroduction: Mighty Care is a community-based geriatric primary care program designed to reach Medicaid eligible adults and elders who are 50 and above, with the purpose of increasing access to care and improve patient quality of life. This is a new initiative for UNTHSC that utilizes mobile teams and clinics to increase access to care by providing appropriate levels of care within the community where the patients live. Generally, research indicates that as people age their quality of life (QOL) declines. The purpose of this study is to do a preliminary analysis of the QOL of the patients seen through this program, and examine age related differences in scores. Methods: QOL was assessed using the 36-item short form health survey (SF-36). The SF 36 is a widely used tool, and possesses good psychometric properties. The SF 36 consists of eight domains, which make up the physical and mental health composite scales. Descriptive statistics were calculated to compare the scores from our sample to the national means. To examine the impact of age, we split the sample into two groups: those 64 and under and 65 and older. Independent t test were used to examine the impact of the age groups on QOL scores. Results: The sample consisted of 229 patients (53 males and 176 females) with a mean age of 61. The average of PCS was 34.78 (SD= 9.87) and MCS was 45.075, falling slightly below the national average. For physical health there was a significant difference in the scores between the two groups, t (227) =-2.458, p=.015, with participants 64 and below (M= 33.7, SD=9.27) having lower scores that the 65 and above group (M=37.15, SD=10.84). For the mental health scores, there was a significant difference between the two groups, t (227)=-3.934, p= .000; suggesting that participants 64 and below (M= 42.71, SD= 13.66) had lower scores those over 65 (M=50.18, SD=12.18). Conclusion: Past research has indicated that age decreases scores on the physical and mental health scales. However, these results indicated that individuals 65 and older reported better QOL than their younger counterparts. One potential explanation for these findings has to do with the fact that at 65 most of these patients are able to apply for Medicare. All participants in this program have Medicaid, however as an individual reaches 65 they are considered dually eligible which means they can have both Medicare and Medicaid. This gives this population access to a wider array of health services and benefits. The data is from baseline QOL measures in the Mighty Care program. This study had a small sample size, therefore more data is needed.Item Relationship Between Uncontrolled Diabetes and Cognition in Mexican American Elders(2017-03-14) Johnson, Leigh; O'Bryant, Sid; Izurieta Munoz, HaydeeHypothesis: Diabetes affects approximately 29.1 million Americans with Mexican Americans being twice as likely to be diagnosed with diabetes. Diabetes is considered a modifiable risk factor for Alzheimer’s disease and cognitive decline. Several studies have shown a link between diabetes and an increased risk of the progression from mild cognitive impairment to Alzheimer’s disease. Although diabetes’ role in cognition is an emerging topic, the majority of research examining diabetes and cognition has focused on non-Hispanic populations. The purpose of this research was to examine the impact of diabetic control on cognition in Mexican Americans. This study was designed to evaluate differences in cognition among controlled and uncontrolled diabetics without cognitive impairment. Past research analyzing the effects of glycemic control on cognition have shown that adults with normal cognition and high HbA1c performed worse on memory and cognition tests than their lower HbA1c counterparts. Methods: Data were obtained from 171 Mexican American participants with diabetes (61 uncontrolled; 110 controlled) enrolled in the Health and Aging Brain among Latino Elders (HABLE) study, a longitudinal study of cognition in elderly Mexican Americans. All participants were classified as having normal cognition. Uncontrolled diabetes was defined as HbA1C levels 9 or greater. Fasting venous blood was drawn from study participants to obtain HbA1C levels and measure long term glycemic control. Cognition level was determined by participant performance on multiple neuropsychological tests evaluating numerous domains of memory: visuospatial, attention, immediate memory, delayed memory and executive function. Results: Independent t tests were conducted to compare cognition among controlled and uncontrolled diabetics. Uncontrolled diabetics performed worse on WMS digit span t(167)=2.1, p Conclusions: Uncontrolled diabetes was associated with poorer performance in the areas of attention and executive functioning among cognitively normal Mexican Americans. No differences were found in immediate and delayed memory, and visuospatial scores. Ongoing work will determine if these links are associated with neuroimaging and other biomarker signatures that may identify those Mexican Americans at greatest risk for cognitive loss associated with poor diabetic control.