Authors: Petersen, Melissa | Hall, James | Parsons, Thomas | Johnson, Leigh | O’Bryant, Sid
Article Type: Research Article
Abstract: Background: Recent work has supported use of blood-based biomarkers in detection of amnestic mild cognitive impairment (MCI). Inclusion of neuropsychological measures has shown promise in enhancing utility of biomarkers to detect disease. Objective: The present study sought to develop cognitive-biomarker profiles for detection of MCI. Methods: Data were analyzed on 463 participants (normal control n = 378; MCI n = 85) from HABLE. Random forest analyses determined proteomic profile of MCI. Separate linear regression analyses determined variance accounted for by select biomarkers per neuropsychological measure. When neuropsychological measure with the least shared variance was identified, it was then combined with select biomarkers …to create a biomarker-cognitive profile. Results: The biomarker-cognitive profile was 90% accurate in detecting MCI. Among amnestic MCI cases, the detection accuracy of the biomarker-cognitive profile was 92% and increased to 94% with demographic variables. Conclusion: The biomarker-cognitive profile for MCI was highly accurate in its detection with use of only five biomarkers. Show more
Keywords: Blood based, biomarkers, mexican american, mild cognitive impairment, neuropsychology
DOI: 10.3233/JAD-191264
Citation: Journal of Alzheimer's Disease, vol. 75, no. 3, pp. 739-750, 2020
Authors: Torres, Stephanie | Alexander, Angel | O’Bryant, Sid | Medina, Luis D.
Article Type: Research Article
Abstract: Background: Various factors, such as age, cardiovascular concerns, and lifestyle patterns, are associated with risk for cognitive decline and Alzheimer’s disease (AD). Risk scores model predictive risk of developing a disease (e.g., dementia, stroke). Many of these scores have been primarily developed in largely non-Hispanic/Latino (non-H/L) White samples and little is known about their applicability in ethno-racially diverse populations. Objective: The primary aim was to examine the relationship between three established risk scores and cognitive performance. These relationships were compared across ethnic groups. Methods: We conducted a cross-sectional study with a multi-ethnic, rural-dwelling group of participants (M age = 61.6±12.6 years, …range: 40–96 years; 373F:168M; 39.7% H/L). The Cardiovascular Risk Factors, Aging and Dementia (CAIDE), Framingham Risk Score (FRS), and Washington Heights-Inwood Columbia Aging Project (WHICAP) score were calculated for each participant. Results: All three scores were significantly associated with cognition in both H/L and non-H/L groups. In H/Ls, cognition was predicted by FRS: β= –0.08, p = 0.022; CAIDE: β= –0.08, p < 0.001; and WHICAP: β= –0.04, p < 0.001. In non-H/Ls, cognition was predicted by FRS: β= –0.11, p < 0.001; CAIDE: β= –0.14, p < 0.001; and WHICAP: β= –0.08, p < 0.001. The strength of this relationship differed between groups for FRS [t(246) = –4.61, p < 0.001] and CAIDE [t(420) = –3.20, p = 0.001], but not for WHICAP [t(384) = –1.03, p = 0.30], which already includes ethnicity in its calculation. Conclusion: These findings support the utility of these three risk scores in predicting cognition while underscoring the need to account for ethnicity. Moreover, our results highlight the importance of cardiovascular and other demographic factors in predicting cognitive outcomes. Show more
Keywords: Aging, cognition, dementia, Hispanic Americans, minority health
DOI: 10.3233/JAD-191284
Citation: Journal of Alzheimer's Disease, vol. 75, no. 3, pp. 1049-1059, 2020
Authors: Edwards, Melissa | Balldin, Valerie Hobson | Hall, James | O'Bryant, Sid
Article Type: Research Article
Abstract: Background: Current work has sought to establish a rapid and cost effective means of screening for Alzheimer’s disease (AD) with the most recent findings showing utility of integrating blood-based biomarkers with cognitive measures. Objective: The current project sought to create a combined biomarker-cognitive profile to detect mild AD. Methods: Data was analyzed from 266 participants (129 AD cases [Early AD n = 93; Very Early AD n = 36]; 137 controls) enrolled in the Texas Alzheimer’s Research and Care Consortium (TARCC). Non-fasting serum samples were collected from each participant and assayed via a multi-plex biomarker assay platform using electrochemiluminescence. Logistic …Regression was utilized to detect early AD using two serum biomarkers (TNFα and IL7), demographic information (age), and one neuropsychological measure (Clock 4-point) as predictor variable. Disease severity was determined via Clinical Dementia Rating (CDR) scale global scores. Results: In the total sample (all levels of CDR scores), the combination of biomarkers, cognitive test score, and demographics yielded the obtained sensitivity (SN) of 0.94, specificity (SP) of 0.90, and an overall accuracy of 0.92. When examining early AD cases (i.e.m CDR = 0.5–1), the biomarker-cognitive profile yielded SN of 0.94, SP of 0.85, and an overall accuracy of 0.91. When restricted to very early AD cases (i.e., CDR = 0.5), the biomarker-cognitive profile yielded SN of 0.97 and SP of 0.72, with an overall accuracy of 0.91. Conclusions: The combination of demographics, two biomarkers, and one cognitive test created a biomarker-cognitive profile that was highly accurate in detecting the presence of AD, even in the very early stages. Show more
Keywords: Alzheimer's disease, biomarkers, molecular, neuropsychology
DOI: 10.3233/JAD-140852
Citation: Journal of Alzheimer's Disease, vol. 42, no. 2, pp. 635-640, 2014
Authors: Clark, Alexandra L. | Haley, Andreana P. | Duarte, Audrey | O’Bryant, Sid
Article Type: Short Communication
Abstract: We examined ethnoracial differences in fatty acid binding protein (FABP)—a family of intracellular lipid carriers—and clarified FABP3 associations with gray and white matter. Relative to Mexican Americans (MAs), FABP3 was higher in Non-Hispanic Whites (NHWS, p < 0.001). Regressions revealed, independent of traditional AD markers, FABP3 was associated with neurodegeneration (B = –0.08, p = 0.003) and WMH burden (B = 0.18, p = 0.03) in MAs, but not in NHWs (ps > 0.18). Findings suggest FABP3 is related to neural health within MAs and highlight its potential as a prognostic marker of brain health in ethnoracially diverse older adults.
Keywords: Alzheimer’s disease, FABP3, Hispanic/Latino, lipid dyshomeostasis, mild cognitive impairment
DOI: 10.3233/JAD-220524
Citation: Journal of Alzheimer's Disease, vol. 90, no. 1, pp. 61-68, 2022
Authors: Edwards, Melissa | Hall, James | Williams, Benjamin | Johnson, Leigh | O’Bryant, Sid
Article Type: Research Article
Abstract: Background: Mexican Americans face a significant health disparity when it comes to Alzheimer’s disease (AD) as they present with higher rates of the disease and develop AD at an earlier age compared to other ethnic groups. Recent work identified a proteomic profile of AD among this population; however, no work to date has sought to examine the biological profile of pre-AD among Mexican Americans. Objective: This study aims to identify an amnestic mild cognitive impairment (aMCI) proteomic profile among Mexican Americans. Methods: Data were analyzed from 284 Mexican American participants (aMCI, n = 73; normal controls, n = 211) from the Health …& Aging Brain among Latino Elders study. Fasting serum samples were analyzed using a multi-plex biomarker assay platform. A biomarker profile was generated using random forest analyses. Results: Among aMCI cases, the biomarker profile was found to be largely inflammatory with the top three markers shown to include TNFα , IL10, and TARC. The overall diagnostic accuracy of the biomarkers in detecting aMCI was 96% (sensitivity = 0.82; specificity = 0.97). Inclusion of clinical variables with the selected biomarkers did not impact the overall detection accuracy (area under the curve = 0.96) but led to a slight improvement in specificity (specificity = 0.99) and decrease in sensitivity (sensitivity = 0.74). Conclusion: The biomarker profile of aMCI was shown to be different from our previously generated AD profile among Mexican Americans, which was largely metabolic in nature. The findings implicate a possible interplay between inflammatory and metabolic processes and additional work is needed to further examine this. Show more
Keywords: Amnestic, biomarker, Mexican American, mild cognitive impairment
DOI: 10.3233/JAD-150553
Citation: Journal of Alzheimer's Disease, vol. 49, no. 1, pp. 221-228, 2016
Authors: Hall, James R. | Wiechmann, April | Johnson, Leigh A. | Edwards, Melissa | O’Bryant, Sid E.
Article Type: Research Article
Abstract: Background: Subjective cognitive complaints in cognitively normal adults have been linked to later cognitive decline and dementia. Research on the characteristics of this group has been conducted on a variety of clinical and community-based populations. The current study focuses on the rapidly expanding population of Mexican-American elders. Objective: The objective of the study is the determination of characteristics of cognitively normal Mexican-Americans with cognitive complaints. Methods: Data on 319 cognitively normal participants in a large-scale community-based study of elderly Mexican-Americans (HABLE) were analyzed comparing those with cognitive complaints with those without on clinical characteristics, affective status, neuropsychological functioning, and proteomic …markers. Results: Those expressing concern about cognitive decline scored lower on the MMSE, were more likely to have significantly more affective symptoms, higher levels of diabetic markers, poorer performance on attention and executive functioning, and a different pattern of inflammatory markers. Conclusion: Although longitudinal research is needed to determine the impact of these differences on later cognition, possible targets for early intervention with Mexican-Americans were identified. Show more
Keywords: Affective symptoms, biomarkers, Mexican-Americans, subjective cognitive complaints
DOI: 10.3233/JAD-170836
Citation: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1485-1492, 2018
Authors: Lista, Simone | O’Bryant, Sid E. | Blennow, Kaj | Dubois, Bruno | Hugon, Jacques | Zetterberg, Henrik | Hampel, Harald
Article Type: Research Article
Abstract: Most forms of Alzheimer’s disease (AD) are sporadic (sAD) or inherited in a non-Mendelian fashion, and less than 1% of cases are autosomal-dominant. Forms of sAD do not exhibit familial aggregation and are characterized by complex genetic and environmental interactions. Recently, the expansion of genomic methodologies, in association with substantially larger combined cohorts, has resulted in various genome-wide association studies that have identified several novel genetic associations of AD. Currently, the most effective methods for establishing the diagnosis of AD are defined by multi-modal pathways, starting with clinical and neuropsychological assessment, cerebrospinal fluid (CSF) analysis, and brain-imaging procedures, all of …which have significant cost- and access-to-care barriers. Consequently, research efforts have focused on the development and validation of non-invasive and generalizable blood-based biomarkers. Among the modalities conceptualized by the systems biology paradigm and utilized in the “exploratory biomarker discovery arena”, proteome analysis has received the most attention. However, metabolomics, lipidomics, transcriptomics, and epigenomics have recently become key modalities in the search for AD biomarkers. Interestingly, biomarker changes for familial AD (fAD), in many but not all cases, seem similar to those for sAD. The integration of neurogenetics with systems biology/physiology-based strategies and high-throughput technologies for molecular profiling is expected to help identify the causes, mechanisms, and biomarkers associated with the various forms of AD. Moreover, in order to hypothesize the dynamic trajectories of biomarkers through disease stages and elucidate the mechanisms of biomarker alterations, updated and more sophisticated theoretical models have been proposed for both sAD and fAD. Show more
Keywords: Alzheimer’s disease, blood-based biomarkers, cerebrospinal fluid biomarkers, familial Alzheimer’s disease, metabolomics/lipidomics, neuroimaging markers, proteomics, sporadic Alzheimer’s disease, systems biology, temporal ordering of biomarkers
DOI: 10.3233/JAD-143006
Citation: Journal of Alzheimer's Disease, vol. 47, no. 2, pp. 291-317, 2015
Authors: Cunningham, Rebecca L. | Singh, Meharvan | O'Bryant, Sid E. | Hall, James R. | Barber, Robert C.
Article Type: Research Article
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 µmol/L), 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. Show more
Keywords: Androgens, antioxidants, homocysteine, luteinizing hormone, Mexican American
DOI: 10.3233/JAD-131994
Citation: Journal of Alzheimer's Disease, vol. 40, no. 3, pp. 563-573, 2014
Authors: Mozdbar, Sima | Petersen, Melissa | Zhang, Fan | Johnson, Leigh | Tolman, Alex | Nyalakonda, Ramyashree | Gutierrez, Alejandra | O’Bryant, Sid
Article Type: Research Article
Abstract: Background: Despite the diagnostic accuracy of advanced neurodiagnostic procedures, the detection of Alzheimer’s disease (AD) remains poor in primary care. There is an urgent need for screening tools to aid in the detection of early AD. Objective: This study examines the predictive ability of structural retinal biomarkers in detecting 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. Results: Data were examined …on n = 91 participants. 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, and the inferior quadrant of the macular retinal nerve fiber layer. Conclusion: The current data provides strong support for continued investigation into structural retinal biomarkers, particularly the retinal nerve fiber layer, as screening tools for AD. Show more
Keywords: Alzheimer’s disease, cognitive impairment, optical coherence tomography, retinal biomarkers
DOI: 10.3233/ADR-220070
Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 749-755, 2022
Authors: Zhang, Fan | Petersen, Melissa | Johnson, Leigh | Hall, James | O’Bryant, Sid E.
Article Type: Research Article
Abstract: Background: There is a need for more reliable diagnostic tools for the early detection of Alzheimer’s disease (AD). This can be a challenge due to a number of factors and logistics making machine learning a viable option. Objective: In this paper, we present on a Support Vector Machine Leave-One-Out Recursive Feature Elimination and Cross Validation (SVM-RFE-LOO) algorithm for use in the early detection of AD and show how the SVM-RFE-LOO method can be used for both classification and prediction of AD. Methods: Data were analyzed on n = 300 participants (n = 150 AD; n = 150 cognitively normal controls). Serum samples were …assayed via a multi-plex biomarker assay platform using electrochemiluminescence (ECL). Results: The SVM-RFE-LOO method reduced the number of features in the model from 21 to 16 biomarkers and achieved an area under the curve (AUC) of 0.980 with a sensitivity of 94.0% and a specificity of 93.3%. When the classification and prediction performance of SVM-RFE-LOO was compared to that of SVM and SVM-RFE, we found similar performance across the models; however, the SVM-RFE-LOO method utilized fewer markers. Conclusion: We found that 1) the SVM-RFE-LOO is suitable for analyzing noisy high-throughput proteomic data, 2) it outperforms SVM-RFE in the robustness to noise and in the ability to recover informative features, and 3) it can improve the prediction performance. Our recursive feature elimination model can serve as a general model for biomarker discovery in other diseases. Show more
Keywords: Alzheimer’s disease, blood biomarkers, machine learning, recursive feature elimination, support vector machine
DOI: 10.3233/JAD-201254
Citation: Journal of Alzheimer's Disease, vol. 79, no. 4, pp. 1691-1700, 2021