Biomarkers of Alzheimer's Disease Among Mexican Americans
ABSTRACT Background: Mexican Americans are the fastest aging segment of the U.S. population, yet little scientific literature exists regarding the Alzheimer's disease (AD) among this segment of the population. The extant literature suggests that biomarkers of AD will vary according to race/ethnicity though no prior work has explicitly studied this possibility. The aim of this study was to create a serum-based biomarker profile of AD among Mexican American. Methods: Data were analyzed from 363 Mexican American participants (49 AD and 314 normal controls) enrolled in the Texas Alzheimer's Research & Care Consortium (TARCC). Non-fasting serum samples were analyzed using a luminex-based multi-plex platform. A biomarker profile was generated using random forest analyses. Results: The biomarker profile of AD among Mexican Americans was different from prior work from non-Hispanic populations with regards to the variable importance plots. In fact, many of the top markers were related to metabolic factors (e.g., FABP, GLP-1, CD40, pancreatic polypeptide, insulin-like-growth factor, and insulin). The biomarker profile was a significant classifier of AD status yielding an area under the receiver operating characteristic curve, sensitivity, and specificity of 0.77, 0.92, and 0.64, respectively. Combining biomarkers with clinical variables yielded a better balance of sensitivity and specificity. Conclusion: The biomarker profile for AD among Mexican American cases is significantly different from that previously identified among non-Hispanic cases from many large-scale studies. This is the first study to explicitly examine and provide support for blood-based biomarkers of AD among Mexican Americans. Areas for future research are highlighted.
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ABSTRACT: Objective: cardiovascular burden is considered a risk factor for the development of cognitive dysfunction and dementia. While this link is well established in the literature, implementing this work in primary care settings remains a challenge. The goal of this study is to examine the utility of the Hachinski Ischemic Scale (HIS) in identifying cognitive dysfunction and diagnosis of mild cognitive impairment (MCI) in an ethnically diverse sample.Methods: data were analysed on 517 participants (211 Mexican Americans and 306 non-Hispanic Whites) recruited from Project FRONTIER, a study of rural health. Neuropsychological measures were utilised to assess for cognitive functioning.Results: among non-Hispanic Whites, HIS scores were significantly related to poorer performance on tasks of global cognition [B (SE) = -0.13 (0.06), P = 0.02], immediate memory [B (SE) = -0.85 (0.26), P < 0.001], attention [B (SE) = -1.6 (0.36), P < 0.001] and executive functioning [B (SE) = 0.46 (0.12), P < 0.001], and significantly predicted diagnosis of MCI [odds ratio (OR) = 1.4; 95% confidence interval (CI) = 1.2-1.6]. For Mexican Americans, HIS scores were significantly related to immediate memory [B (SE) = -0.78 (0.28), P = 0.01], attention [B (SE) = -0.74 (0.36), P = 0.04] and executive functioning [B (SE) = 0.37 (0.14), P = 0.01]; however, HIS scores were not significantly related to diagnosis of MCI in Mexican Americans (OR = 1.2, 95% CI = 0.96-1.4, P = 0.116).Conclusion: HIS scores were related to cognitive functioning; however, these results differed by ethnicity. It is possible that these findings indicate that vascular factors may increase risk for MCI among non-Hispanic Whites but not for Mexican Americans. These findings are consistent with past research that suggests risk factors for MCI may differ by ethnicity.Age and Ageing 12/2013; 43(3). DOI:10.1093/ageing/aft189 · 3.11 Impact Factor
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ABSTRACT: We have used structural equation models to explicitly distinguish functional status, and therefore “dementia-relevant” variance in cognitive task performance (i.e., “δ”) from that which is unrelated to a dementing process. Our approach results in a relatively “error-free” continuous variable that can serve as a dementia-specific phenotype. In this study, we associate δ with cytokines and other serum biomarkers in a well characterized Alzheimer's disease cohort, the Texas Alzheimer's Research and Care Consortium. Independent of covariates, δ is associated significantly with 12 serum biomarkers. These associations appear to be specific to non-Hispanic white participants.Neurobiology of aging 02/2014; 35(2):336–344. DOI:10.1016/j.neurobiolaging.2013.08.006 · 4.85 Impact Factor
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ABSTRACT: Background: The use of testosterone among aging men has been increasing, but results from studies addressing the effectiveness of testosterone replacement therapy have been equivocal. Objective: Given our prior pre-clinical studies that reported a major influence of oxidative stress on testosterone's neuroprotective effects, we investigated whether the negative effects of testosterone on brain function were predicted by oxidative load. Methods: In order to test our hypothesis, we determined whether circulating total testosterone and luteinizing hormone correlated with cognition in a subset of the Texas Alzheimer's Research & Care Consortium (TARCC) cohort, consisting of Caucasian (n = 116) and Mexican-American (n = 117) men. We also assessed whether oxidative stress (as indexed by homocysteine levels) modified this relationship between sex hormones and cognition, and whether the levels of two antioxidants, superoxide dismutase-1 and glutathione S-transferase (GST), varied as a function of circulating testosterone. Results: In a low oxidative stress environment, testosterone was positively associated with the level of the antioxidant, GST, while no deleterious effects on cognitive function were noted. In contrast, under conditions of high oxidative stress (homocysteine levels >12 μM), testosterone and luteinizing hormone were associated with cognitive impairment, but only among Caucasians. The ethnic difference was attributed to significantly higher GST levels among Mexican-Americans. Conclusion: While testosterone may be beneficial under conditions of low oxidative stress, testosterone appears to have negative consequences under conditions of elevated oxidative stress, but only in Caucasians. Mexican-Americans, however, were protected from any deleterious effects of testosterone, potentially due to higher levels of endogenous antioxidant defenses such as GST.Journal of Alzheimer's disease: JAD 02/2014; 40(3). DOI:10.3233/JAD-131994 · 3.61 Impact Factor