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1.  Risk factors for mild cognitive impairment among Mexican Americans 
Background
While a great deal of literature has focused on risk factors for Mild Cognitive Impairment (MCI), little published work examines risk for MCI among Mexican Americans.
Methods
Data from 1628 participants (non-Hispanic n= 1002; Mexican American n=626) were analyzed from two ongoing studies of cognitive aging and Alzheimer’s disease, Project FRONTIER and TARCC.
Results
When looking at the full cohorts (non-Hispanic and Mexican American), age, education, APOE ε4 status and gender were consistently related to MCI diagnosis across the two cohorts. However, when split by ethnicity advancing age was the only significant risk factor for MCI among Mexican Americans across both cohorts.
Conclusions
The current data suggests that many of the previously established risk factors for MCI among non-Hispanic cohorts may not be predictive of MCI among Mexican Americans and point to the need for additional work aimed at understanding factors related to cognitive aging among this underserved segment of the population.
doi:10.1016/j.jalz.2012.12.007
PMCID: PMC3737282  PMID: 23643456
Mexican American; Mild Cognitive Impairment; cognition; Alzheimer’s disease; ethnicity; cross-cultural; risk factors
2.  Androgen receptor gene and gender specific Alzheimer’s disease 
Neurobiology of aging  2013;34(8):2077.e19-2077.e20.
Women are at a twofold risk of developing late onset Alzheimer’s disease (LOAD) (onset ≥65 years of age) compared to men. During perimenopausal years, women undergo hormonal changes that are accompanied by metabolic, cardiovascular and inflammatory changes. These all together have been suggested as risk factors for LOAD. However, not all perimenopausal women develop AD; we hypothesize that certain genetic factors might underlie the increased susceptibility for developing AD in postmenopausal women. We investigated the androgen receptor (AR) gene in a clinical cohort of male and female AD patients and normal controls by sequencing all coding exons and evaluating the length and distribution of the CAG repeat in exon 1. We could not establish a correlation between the repeat length, gender and the disease status, nor did we identify possible pathogenic variants. AR is located on the X chromosome; in order to assess its role in AD, X-inactivation patterns will need to be studied to directly correlate the actual expressed repeat length to a possible sex specific phenotypic effect.
doi:10.1016/j.neurobiolaging.2013.02.017
PMCID: PMC4012749  PMID: 23545426
Alzheimer’s disease; androgen receptor; menopause; X-inactivation; epigenetics
3.  Acetaminophen Dose Does Not Predict Outcome in Acetaminophen-Induced Acute Liver Failure 
Background
Acetaminophen is a dose-dependent toxin. Prognosis in severe acute liver injury is related presumably in part to the dose ingested. We sought to assess the value of acetaminophen dosing information in patients with acute liver failure (ALF) due to acetaminophen toxicity to determine the role of dose as a prognostic indicator.
Methods
Prospective data from 113 patients with ALF having single-time-point ingestions of acetaminophen were analyzed. Multivariate and χ2 tests were used to determine the relationship of dose to clinical outcome. We also used the Mann-Whitney U test to compare prognosis and survival in ALF with acetaminophen dose ingested.
Results
Multivariate and χ2 analyses failed to show any relationship between acetaminophen dose and spontaneous survival. A separate analysis showed no correlation between acetaminophen dose and clinical prognostic indicators.
Conclusions
Dose of acetaminophen ingested did not seem to play a role in prognosis. The most important prognostic factor was coma grade on admission to study. Acetaminophen dosing information is not always obtainable. When it is, it adds little to the clinical assessment. Severity of encephalopathy is a more reliable indicator of prognosis in these critically ill patients.
doi:10.231/JIM.0b013e3181db8764
PMCID: PMC3618971  PMID: 20305573
acetaminophen; acute liver failure; N-acetylcysteine
4.  Effect of Spironolactone on Patients With Atrial Fibrillation and Structural Heart Disease 
Clinical cardiology  2011;34(7):415-419.
Background
Several studies have shown that the modulation of fibrotic scar in cardiac diseases has beneficial effects on cardiac arrhythmias. In addition, recent reports suggest a potential role of mineralocorticoid receptor upregulation in atrial fibrillation (AF). The role of spironolactone, a mineralocorticoid receptor blocker and a potent antifibrotic agent, in AF is as yet unexplored. The aim of this study was to determine if spironolactone, a mineralocorticoid receptor blocker with potent antifibrotic properties, has beneficial effects on AF.
Hypothesis
Spironolactone therapy in patients with atrial fibrillation provides additional clinical benefits in addition to the current conventional pharmacological agents.
Methods
A comprehensive retrospective analysis was performed on 83 patients with AF, including 23 who were treated with spironolactone for ≥ 3 months. The combined primary outcome of hospitalization for AF or direct current cardioversion (DCCV) was compared between patients treated with spironolactone in addition to the usual care for AF and those receiving conventional medical therapy alone.
Results
Patients receiving spironolactone had significantly fewer primary outcome events (AF-related hospitalizations or DCCV) (22% vs 53%, P = 0.027).
Conclusions
Spironolactone therapy is associated with a reduction in the burden of AF, as reflected by a combination of hospitalizations for AF and DCCV. Larger randomized controlled studies should be performed to evaluate the efficacy and safety of spironolactone as an adjunctive therapy for patients with AF.
doi:10.1002/clc.20914
PMCID: PMC3617486  PMID: 21674535
5.  A Blood-Based Algorithm for the Detection of Alzheimer's Disease 
Background
We previously created a serum-based algorithm that yielded excellent diagnostic accuracy in Alzheimer's disease. The current project was designed to refine that algorithm by reducing the number of serum proteins and by including clinical labs. The link between the biomarker risk score and neuropsychological performance was also examined.
Methods
Serum-protein multiplex biomarker data from 197 patients diagnosed with Alzheimer's disease and 203 cognitively normal controls from the Texas Alzheimer's Research Consortium were analyzed. The 30 markers identified as the most important from our initial analyses and clinical labs were utilized to create the algorithm.
Results
The 30-protein risk score yielded a sensitivity, specificity, and AUC of 0.88, 0.82, and 0.91, respectively. When combined with demographic data and clinical labs, the algorithm yielded a sensitivity, specificity, and AUC of 0.89, 0.85, and 0.94, respectively. In linear regression models, the biomarker risk score was most strongly related to neuropsychological tests of language and memory.
Conclusions
Our previously published diagnostic algorithm can be restricted to only 30 serum proteins and still retain excellent diagnostic accuracy. Additionally, the revised biomarker risk score is significantly related to neuropsychological test performance.
doi:10.1159/000330750
PMCID: PMC3169374  PMID: 21865746
Algorithm, blood-based; Alzheimer's disease; Diagnosis
6.  Staging Dementia Using Clinical Dementia Rating Scale Sum of Boxes Scores 
Archives of neurology  2008;65(8):1091-1095.
Background
The Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score is commonly used, although the utility regarding this score in staging dementia severity is not well established.
Obiective
To investigate the effectiveness of CDRSOB scores in staging dementia severity compared with the global CDR score.
Design
Retrospective study.
Setting
Texas Alzheimer's Research Consortium minimum data set cohort.
Participants
A total of 1577 participants (110 controls, 202 patients with mild cognitive impairment, and 1265 patients with probable Alzheimer disease) were available for analysis.
Main Outcome Measures
Receiver operating characteristic curves were generated from a derivation sample to determine optimal cutoff scores and ranges, which were then applied to the validation sample.
Results
Optimal ranges of CDR-SOB scores corresponding to the global CDR scores were 0.5 to 4.0 for a global score of 0.5, 4.5 to 9.0 for a global score of 1.O, 9.5 to 15.5 for a global score of 2.0, and 16.0 to 18.0 for a global score of 3.0. When applied to the validation sample, κ scores ranged from 0.86 to 0.94 (P <.001 for all), with 93.0% of the participants falling within the new staging categories.
Conclusions
The CDR-SOB score compares well with the global CDR score for dementia staging. Owing to the increased range of values, the CDR-SOB score offers several advantages over the global score, including increased utility in tracking changes within and between stages of dementia severity. Interpretive guidelines for CDR-SOB scores are provided.
doi:10.1001/archneur.65.8.1091
PMCID: PMC3409562  PMID: 18695059
7.  Elevated Serum Pesticide Levels and Risk of Parkinson Disease 
Archives of Neurology  2009;66(7):870-875.
Background
Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains.
Objective
To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD.
Design
Case-control study.
Setting
An academic medical center.
Participants
Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease.
Main Outcome Measures
Levels of 16 organochlorine pesticides in serum samples.
Results
β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD.
Conclusions
These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD.
doi:10.1001/archneurol.2009.89
PMCID: PMC3383784  PMID: 19597089
8.  A Serum Protein-Based Algorithm for the Detection of Alzheimer's Disease 
Archives of neurology  2010;67(9):1077-1081.
Background
Alzheimer's disease (AD) is the most common form of age-related dementia and one of the most serious health problems in the industrialized world. Biomarker approaches to diagnostics would be more time and cost effective and may also be useful for identifying endophenotypes within AD patient populations.
Methods
We analyzed serum protein-based multiplex biomarker data from 197 patients diagnosed with AD and 203 controls from a longitudinal study of Alzheimer's disease being conducted by the Texas Alzheimer's Research Consortium to develop an algorithm that separates AD from controls. The total sample was randomized equally into training and test sets and random forest methods were applied to the training set to create a biomarker risk score.
Findings
The biomarker risk score had a sensitivity and specificity of 0.80 and 0.91, respectively and an AUC of 0.91 in detecting AD. When age, gender, education, and APOE status were added to the algorithm, the sensitivity, specificity, and AUC were 0.94, 0.84, and 0.95, respectively.
Interpretation
These initial data suggest that serum protein-based biomarkers can be combined with clinical information to accurately classify AD. Of note, a disproportionate number of inflammatory and vascular markers were weighted most heavily in analyses. Additionally, these markers consistently distinguished cases from controls in SAM, logistic regression and Wilcoxon analyses, suggesting the existence of an inflammatory-related endophenotype of AD that may provide targeted therapeutic opportunities for this subset of patients.
doi:10.1001/archneurol.2010.215
PMCID: PMC3069805  PMID: 20837851
9.  UTHSCD-ISP: Interactive Statistical Programs in a Medical Environment 
Interactive statistical programs have been developed at The University of Texas Health Science Center at Dallas (UTHSCD) to handle the common as well as special statistical data analysis needs in medical research. UTHSCD-ISP is user-friendly; it can be accessed from a CRT terminal with a minimum of prior instruction. The user can step through the program by answering questions with a one word response (“yes,” “no,” etc.) or with a code number to designate a specific response. Data are entered interactively or called from an existing file. Information regarding the appropriate statistical analysis choice is given when alternative analyses are provided. Significance levels or references to tables are given and references for further reading are listed. Graphical output is included with several of the programs and the results can be obtained in printed form at the option of the user. Currently, the UTHSCD-ISP programs are available on the DEC-10 and DEC-20 computers.
PMCID: PMC2580329

Results 1-9 (9)