RESUMEN
INTRODUCTION: Neighborhood socioeconomic status (NSES) has been linked with overall health, and this study will evaluate whether NSES is cross-sectionally associated with cognition in non-Hispanic whites (NHWs) and Mexican Americans (MAs) from the Health and Aging Brain: Health Disparities Study (HABS-HD). METHODS: The HABS-HD is a longitudinal study conducted at the University of North Texas Health Science Center. The final sample analyzed (n = 1,312) were 50 years or older, with unimpaired cognition, and underwent an interview, neuropsychological examination, imaging, and blood draw. NSES was measured using the national area deprivation index (ADI) percentile ranking, which considered socioeconomic variables. Executive function and processing speed were assessed by the trail making tests (A and B) and the digit-symbol substitution test, respectively. Linear regression was used to assess the association of ADI and cognitive measures. RESULTS: MAs were younger, more likely to be female, less educated, had higher ADI scores, performed worse on trails B (all p < 0.05), and had lower prevalence of APOE4 + when compared to NHWs (p < 0.0001). A higher percentage of MAs lived in the most deprived neighborhoods than NHWs. For NHWs, ADI did not predict trails B or DSS scores, after adjusting for demographic variables and APOE4. For MAs, ADI predicted trails A, trails B, and DSS after adjusting for demographic covariates and APOE4 status. CONCLUSION: Our study revealed that living in an area of higher deprivation was associated with lower cognitive function in MAs but not in NHWs, which is important to consider in future interventions to slow cognitive decline.
Asunto(s)
Envejecimiento , Función Ejecutiva , Americanos Mexicanos , Pruebas Neuropsicológicas , Clase Social , Humanos , Femenino , Masculino , Anciano , Americanos Mexicanos/psicología , Americanos Mexicanos/estadística & datos numéricos , Persona de Mediana Edad , Estudios Longitudinales , Envejecimiento/psicología , Disparidades en el Estado de Salud , Cognición/fisiología , Características del Vecindario , Población Blanca/psicología , Población Blanca/estadística & datos numéricos , Estudios Transversales , Estudios de Cohortes , Anciano de 80 o más Años , Características de la Residencia , Texas/epidemiología , Velocidad de ProcesamientoRESUMEN
INTRODUCTION: Despite the clinical implementation, there remain significant gaps in our knowledge regarding the impact of race/ethnicity or common medical comorbidity on plasma Alzheimer's disease (AD) biomarkers. METHODS: Plasma biomarkers of amyloid beta (Aß)40, Aß42 , total tau, and neurofilament light chain (NfL) were measured across cognitively normal Mexican Americans (n = 445) and non-Hispanic Whites (n = 520). RESULTS: Dyslipidemia was associated with elevated Aß40 (P = .01) and Aß42 (P = .001) while hypertension was associated with elevated Aß40 (P = .003), Aß42 (P < .001), and total tau (P = .002) levels. Diabetes was associated with higher Aß40 (P < .001), Aß42 (P < .001), total tau (P < .001), and NfL (P < .001) levels. Chronic kidney disease (CKD) was associated with elevations in Aß40 (P < .001), Aß42 (P < .001), total tau (P < .001), and NfL (P < .001) levels. Mexican Americans had significantly lower Aß40 (P < .001) and higher total tau (P = .005) levels. DISCUSSION: Plasma AD biomarkers vary significantly in association with common medical comorbidities as well as ethnicity. These findings are important for those using these biomarkers in clinical practice and clinical trials.
Asunto(s)
Enfermedad de Alzheimer , Humanos , Péptidos beta-Amiloides , Etnicidad , Proteínas tau , Biomarcadores , Comorbilidad , Fragmentos de PéptidosRESUMEN
INTRODUCTION: The influence of apolipoprotein E (APOE) genotype on mild cognitive impairment (MCI) and Alzheimer's disease (AD) is well studied in the non-Hispanic white (NHW) population but not in the Hispanic population. Additionally, health risk factors such as hypertension, stroke, and depression may also differ between the two populations. METHODS: We combined three data sets (National Alzheimer's Coordinating Center [NACC], Alzheimer's Disease Neuroimaging Initiative [ADNI], Health and Aging Brain Study: Health Disparities [HABS-HD]) and compared risk factors for MCI and AD between Hispanic and NHW participants, with a total of 24,268 participants (11.1% Hispanic). RESULTS: APOEε4 was associated with fewer all-cause MCI cases in Hispanic participants (Hispanic odds ratio [OR]: 1.114; NHW OR: 1.453), and APOEε2 (Hispanic OR: 1.224; NHW OR: 0.592) and depression (Hispanic OR: 2.817; NHW OR: 1.847) were associated with more AD cases in Hispanic participants. DISCUSSION: APOEε2 may not be protective for AD in Hispanic participants and Hispanic participants with depression may face a higher risk for AD. HIGHLIGHTS: GAAIN allows for discovery of data sets to use in secondary analyses. APOEε2 was not protective for AD in Hispanic participants. APOEε4 was associated with fewer MCI cases in Hispanic participants. Depression was associated with more AD cases in Hispanic participants.
Asunto(s)
Enfermedad de Alzheimer , Apolipoproteínas E , Disfunción Cognitiva , Hispánicos o Latinos , Población Blanca , Humanos , Envejecimiento , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Apolipoproteína E2/genética , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/genética , Hispánicos o Latinos/genética , Hispánicos o Latinos/psicología , Hispánicos o Latinos/estadística & datos numéricos , Factores de Riesgo , Población Blanca/genética , Población Blanca/psicología , Población Blanca/estadística & datos numéricosRESUMEN
INTRODUCTION: The APOEε4 allele is the single strongest genetic risk for late-onset Alzheimer's disease (AD). Prior work demonstrates that not only the APOEε4 allele varies by race/ethnicity but also the risk for AD and cognitive impairment conveyed by the APOEε4 allele varies by the racial/ethnic group as well as genetic ancestry. Here, we sought to examine the link between the APOEε4 and neuropsychological functioning among Mexican Americans (MAs). METHODS: Data were examined from 1,633 (852 MAs and 781 non-Hispanic Whites [NHWs]) participants of the Health & Aging Brain Study - Health Disparities (HABS-HD) and were enrolled with all requisite data to be included into the current analyses. RESULTS: The frequency of both ε4 and ε2 alleles was significantly lower among MAs as compared to NHWs. Among MAs, APOEε4 allele presence was associated specifically with poorer immediate and delayed memory (Wechsler Memory Scale - Third Edition [WMS-III] Logical Memory and Spanish-English Verbal Learning Test [SEVLT]). Among NHWs, APOEε4 allele presence was associated with poorer immediate and delayed memory as well as worse executive functioning (Trials B) and verbal fluency (Animal naming). DISCUSSION/CONCLUSION: The APOEε4 allele was associated with poorer cognition across multiple domains among NHWs; however, allele presence was specifically associated with poorer memory performance among MAs. When combined with prior work, the current findings demonstrate that the risk factors associated with cognitive dysfunction differ among MAs as compared to NHWs and require additional investigation.
Asunto(s)
Enfermedad de Alzheimer , Apolipoproteína E4 , Envejecimiento/genética , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/psicología , Apolipoproteína E4/genética , Encéfalo , Etnicidad , Humanos , Americanos Mexicanos/genética , Pruebas NeuropsicológicasRESUMEN
INTRODUCTION: Representation of Mexican Americans in Alzheimer's disease (AD) clinical research has been extremely poor. METHODS: Data were examined from the ongoing community-based, multi-ethnic Health & Aging Brain among Latino Elders (HABLE) study. Participants underwent functional exams, clinical labs, neuropsychological testing, and 3T magnetic resonance imaging of the brain. Fasting proteomic markers were examined for predicting mild cognitive impairment (MCI) and AD using support vector machine models. RESULTS: Data were examined from n = 1649 participants (Mexican American n = 866; non-Hispanic White n = 783). Proteomic profiles were highly accurate in detecting MCI (area under the curve [AUC] = 0.91) and dementia (AUC = 0.95). The proteomic profiles varied significantly between ethnic groups and disease state. Negative predictive value was excellent for ruling out MCI and dementia across ethnic groups. DISCUSSION: A blood-based screening tool can serve as a method for increasing access to state-of-the-art AD clinical research by bridging between community-based and clinic-based settings.
Asunto(s)
Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/diagnóstico , Disfunción Cognitiva/diagnóstico , Vida Independiente , Tamizaje Masivo , Americanos Mexicanos/estadística & datos numéricos , Población Blanca/estadística & datos numéricos , Anciano , Enfermedad de Alzheimer/etnología , Biomarcadores/sangre , Disfunción Cognitiva/sangre , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Selección de Paciente , ProteómicaRESUMEN
INTRODUCTION: Alzheimer's disease (AD) is the most frequently occurring neurodegenerative disease; however, little work has been conducted examining biomarkers of AD among Mexican Americans. Here, we examined diffusion tensor MRI marker profiles for detecting mild cognitive impairment (MCI) and dementia in a multi-ethnic cohort. METHODS: 3T MRI measures of fractional anisotropy (FA) were examined among 1,636 participants of the ongoing community-based Health & Aging Brain among Latino Elders (HABLE) community-based study (Mexican American n = 851; non-Hispanic white n = 785). RESULTS: The FA profile was highly accurate in detecting both MCI (area under the receiver operating characteristic curve [AUC] = 0.99) and dementia (AUC = 0.98). However, the FA profile varied significantly not only between diagnostic groups but also between Mexican Americans and non-Hispanic whites. CONCLUSION: Findings suggest that diffusion tensor imaging markers may have a role in the neurodiagnostic process for detecting MCI and dementia among diverse populations.
Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedades Neurodegenerativas , Anciano , Envejecimiento , Enfermedad de Alzheimer/diagnóstico por imagen , Anisotropía , Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Imagen de Difusión Tensora , Humanos , Americanos MexicanosRESUMEN
BACKGROUND: Mexican Americans are at increased risk of developing mild cognitive impairment (MCI) and Alzheimer's disease compared to non-Hispanic whites. This study sought to examine the relationship between vascular risk, depression, and cognition in Mexican American elders. METHODS: Data from 470 (390 normal controls, 80 MCI patients) Mexican Americans enrolled in the Health and Aging Brain among Latino Elders (HABLE) study were used. The cardiovascular risk was assessed by the Framingham Risk Score. Cognition was assessed with a neuropsychological battery, and depression was assessed based on scores from the Geriatric Depression Scale (GDS). ANOVAs were utilized to determine the differences in neuropsychological scores of normal controls with and without depression and CVD risk (low vs. high). Follow-up logistic regression was conducted to determine MCI risk. RESULTS: The results of this study indicated that comorbid depression and a high CVD risk were associated with poorer cognitive performance in Mexican Americans. Depressed women with high CVD risk were more likely to have executive dysfunction, language deficits, and poorer global cognition than nondepressed women with a high CVD risk. In Mexican American men, those with a high vascular risk and depression were more likely to have executive dysfunction and poorer immediate memory than the nondepressed high-risk group. Higher GDS scores (OR = 1.10; 95% CI 1.02-1.10, p = 0.001) and higher vascular risk scores (OR = 1.05; 95% CI 1.02-1.10, p = 0.001) significantly predicted MCI status in Mexican Americans. CONCLUSION: The results of this study indicated that comorbid depression and a high CVD risk were associated with poorer cognitive performance and increased risk of MCI in Mexican Americans.
Asunto(s)
Enfermedad de Alzheimer , Enfermedades Cardiovasculares , Disfunción Cognitiva , Depresión , Americanos Mexicanos/psicología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/etnología , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/epidemiología , Cognición/fisiología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etnología , Disfunción Cognitiva/etiología , Comorbilidad , Depresión/diagnóstico , Depresión/etnología , Depresión/etiología , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Pronóstico , Medición de Riesgo , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: This study explored the combined impact of depression and inflammation on memory functioning among Mexican-American adults and elders. METHODS: Data were analyzed from 381 participants of the Health and Aging Brain study among Latino Elders (HABLE). Fasting serum samples were collected and assayed in duplicate using electrochemiluminesce on the SECTOR Imager 2400A from Meso Scale Discovery. Positive DepE (depression endophenotype) was codified as any score >1 on a five-point scale based on the GDS-30. Inflammation was determined by TNFα levels and categorized by tertiles (1st, 2nd, 3rd). WMS-III LMI and LMII as well as CERAD were utilized as measures of memory. ANOVAs examined group differences between positive DepE and inflammation tertiles with neuropsychological scale scores as outcome variables. Logistic regressions were used to examine level of inflammation and DepE positive status on the risk for MCI. RESULTS: Positive DepE as well as higher inflammation were both independently found to be associated with lower memory scores. Among DepE positive, those who were high in inflammation (3rd tertile) were found to perform significantly worse on WMS-III LM I (F = 4.75, p = 0.003), WMS-III LM II (F = 8.18, p < 0.001), and CERAD List Learning (F = 17.37, p < 0.001) when compared to those low on inflammation (1st tertile). The combination of DepE positive and highest tertile of inflammation was associated with increased risk for MCI diagnosis (OR = 6.06; 95% CI = 3.9-11.2, p < 0.001). CONCLUSION: Presence of elevated inflammation and positive DepE scores increased risk for worse memory among Mexican-American older adults. Additionally, the combination of DepE and high inflammation was associated with increased risk for MCI diagnosis. This work suggests that depression and inflammation are independently associated with worse memory among Mexican-American adults and elders; however, the combination of both increases risk for poorer memory beyond either alone.
Asunto(s)
Disfunción Cognitiva/etnología , Depresión/etnología , Inflamación/etnología , Trastornos de la Memoria/etnología , Americanos Mexicanos , Anciano , Disfunción Cognitiva/complicaciones , Estudios de Cohortes , Depresión/complicaciones , Femenino , Humanos , Inflamación/complicaciones , Modelos Logísticos , Masculino , Trastornos de la Memoria/complicaciones , Persona de Mediana Edad , Pruebas Neuropsicológicas , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer's disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patient acceptance. Despite these advantages and increased research efforts, the field has been hampered by lack of reproducibility and an unclear path for moving basic discovery toward clinical utilization. Here we reviewed the recent literature on blood-based biomarkers in AD to provide a current state of the art. In addition, a collaborative model is proposed that leverages academic and industry strengths to facilitate the field in moving past discovery only work and toward clinical use. Key resources are provided. This new public-private partnership model is intended to circumvent the traditional handoff model and provide a clear and useful paradigm for the advancement of biomarker science in AD and other neurodegenerative diseases.
Asunto(s)
Enfermedad de Alzheimer/sangre , Biomarcadores/sangre , Conducta Cooperativa , Asociación entre el Sector Público-Privado , Femenino , Humanos , Masculino , Reproducibilidad de los ResultadosRESUMEN
During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/fisiopatología , Encéfalo/patología , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Animales , Encéfalo/diagnóstico por imagen , Progresión de la Enfermedad , HumanosRESUMEN
OBJECTIVE: The objective was to evaluate in a cognitively normal population the utility of an endophenotype of the depression-cognition link previously shown to be related to cognitive functioning in mild cognitive impairment and Alzheimer's disease. METHODS: The data of 460 cognitively normal adults aged 32-92 years (M = 63.5, standard deviation = 9.24) from the Western Australian Memory Study with the Cross-national comparisons of the Cambridge Cognitive Examination-revised (CAMCOG-R) scores and 30-item Geriatric Depression Scale (GDS) scores were analyzed to determine the relationship between the five-item depressive endophenotype (DepE) scale drawn from the GDS and level of performance on a measure of cognitive functioning. RESULTS: For the entire sample, there was a nonsignificant trend toward a negative relationship between DepE and CAMCOG-R scores. When analyzed for those 65 years and older, there was a significant negative relationship between the two measures (p = 0.001) with DepE scores significantly increasing the risk for performing more poorly on the CAMCOG-R (odds ratio = 1.53). Analysis of data for those 70 years and older showed that DepE was the only predictor significantly related to poorer CAMCOG-R performance (p = 0.001). For the 70 years and older group, DepE scores significantly increased the risk of poorer CAMCOG-R scores (odds ratio = 2.23). Analysis of the entire sample on the basis of ApoEε4 carrier status revealed that DepE scores were significantly negatively related only to ApoEε4 noncarrier regardless of age. CONCLUSIONS: Elevated DepE scores are associated with poor neuropsychological performance among cognitively normal older adults. Use of the DepE may allow for the identification of a subset of older adults where depression is a primary factor in cognitive decline and who may benefit from antidepressant therapies.
Asunto(s)
Disfunción Cognitiva/diagnóstico , Trastorno Depresivo/complicaciones , Endofenotipos , Adulto , Anciano , Anciano de 80 o más Años , Apolipoproteínas E/genética , Disfunción Cognitiva/genética , Disfunción Cognitiva/psicología , Trastorno Depresivo/psicología , Femenino , Psiquiatría Geriátrica , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Australia OccidentalRESUMEN
Current state-of-the-art diagnostic measures of Alzheimer's disease (AD) are invasive (cerebrospinal fluid analysis), expensive (neuroimaging) and time-consuming (neuropsychological assessment) and thus have limited accessibility as frontline screening and diagnostic tools for AD. Thus, there is an increasing need for additional noninvasive and/or cost-effective tools, allowing identification of subjects in the preclinical or early clinical stages of AD who could be suitable for further cognitive evaluation and dementia diagnostics. Implementation of such tests may facilitate early and potentially more effective therapeutic and preventative strategies for AD. Before applying them in clinical practice, these tools should be examined in ongoing large clinical trials. This review will summarize and highlight the most promising screening tools including neuropsychometric, clinical, blood, and neurophysiological tests.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Pruebas Diagnósticas de Rutina/métodos , Diagnóstico Precoz , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/complicaciones , Depresión/etiología , Pruebas Diagnósticas de Rutina/normas , Electrofisiología , Ojo/fisiopatología , Marcha/fisiología , Humanos , Trastornos de la Memoria/etiologíaRESUMEN
The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer's disease (AD). Blood-based biomarkers have potential to overcome access and cost barriers and greatly facilitate advanced neuroimaging and cerebrospinal fluid biomarker approaches. Despite the fact that preanalytical processing is the largest source of variability in laboratory testing, there are no currently available standardized preanalytical guidelines. The current international working group provides the initial starting point for such guidelines for standardized operating procedures (SOPs). It is anticipated that these guidelines will be updated as additional research findings become available. The statement provides (1) a synopsis of selected preanalytical methods utilized in many international AD cohort studies, (2) initial draft guidelines/SOPs for preanalytical methods, and (3) a list of required methodological information and protocols to be made available for publications in the field to foster cross-validation across cohorts and laboratories.
Asunto(s)
Enfermedad de Alzheimer/sangre , Biomarcadores/sangre , Guías como Asunto/normas , Enfermedad de Alzheimer/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , HumanosRESUMEN
BACKGROUND: Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are a major factor in nursing home placement and a primary cause of stress for caregivers. Elevated cholesterol has been linked to psychiatric disorders and has been shown to be a risk factor for AD and to impact disease progression. The present study investigated the relationship between cholesterol and NPS in AD. METHODS: Data on cholesterol and NPS from 220 individuals (144 females, 76 males) with mild-to-moderate AD from the Texas Alzheimer's Research and Care Consortium (TARCC) cohort were analyzed. The total number of NPS and symptoms of hyperactivity, psychosis, affect and apathy were evaluated. Groups based on total cholesterol (TC; ≥200 vs. <200 mg/dl) were compared with regard to NPS. The impact of gender was also assessed. RESULTS: Individuals with high TC had lower MMSE scores as well as significantly more NPS and more symptoms of psychosis. When stratified by gender, males with high TC had significantly more NPS than females with high TC or than males or females with low TC. CONCLUSION: The role of elevated cholesterol in the occurrence of NPS in AD appears to be gender and symptom specific. A cross-validation of these findings will have implications for possible treatment interventions, especially for males with high TC.
Asunto(s)
Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/psicología , Colesterol/sangre , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Femenino , Humanos , Estudios Longitudinales , Masculino , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Factores Sexuales , Encuestas y Cuestionarios , TexasRESUMEN
BACKGROUND: Prior work on the link between blood-based biomarkers and cognitive status has largely been based on dichotomous classifications rather than detailed neuropsychological functioning. The current project was designed to create serum-based biomarker algorithms that predict neuropsychological test performance. METHODS: A battery of neuropsychological measures was administered. Random forest analyses were utilized to create neuropsychological test-specific biomarker risk scores in a training set that were entered into linear regression models predicting the respective test scores in the test set. Serum multiplex biomarker data were analyzed on 108 proteins from 395 participants (197 Alzheimer patients and 198 controls) from the Texas Alzheimer's Research and Care Consortium. RESULTS: The biomarker risk scores were significant predictors (p < 0.05) of scores on all neuropsychological tests. With the exception of premorbid intellectual status (6.6%), the biomarker risk scores alone accounted for a minimum of 12.9% of the variance in neuropsychological scores. Biomarker algorithms (biomarker risk scores and demographics) accounted for substantially more variance in scores. Review of the variable importance plots indicated differential patterns of biomarker significance for each test, suggesting the possibility of domain-specific biomarker algorithms. CONCLUSIONS: Our findings provide proof of concept for a novel area of scientific discovery, which we term 'molecular neuropsychology'.
Asunto(s)
Algoritmos , Biomarcadores/sangre , Neuropsicología/métodos , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/psicología , Cognición/fisiología , Estudios de Cohortes , Femenino , Humanos , Inteligencia , Modelos Lineales , Masculino , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
Exposure to arsenic causes many diseases. Most Americans in rural areas use groundwater for drinking, which may contain arsenic above the currently allowable level, 10µg/L. It is cost-effective to estimate groundwater arsenic levels based on data from wells with known arsenic concentrations. We compared the accuracy of several commonly used interpolation methods in estimating arsenic concentrations in >8000 wells in Texas by the leave-one-out-cross-validation technique. Correlation coefficient between measured and estimated arsenic levels was greater with inverse distance weighted (IDW) than kriging Gaussian, kriging spherical or cokriging interpolations when analyzing data from wells in the entire Texas (p<0.0001). Correlation coefficient was significantly lower with cokriging than any other methods (p<0.006) for wells in Texas, east Texas or the Edwards aquifer. Correlation coefficient was significantly greater for wells in southwestern Texas Panhandle than in east Texas, and was higher for wells in Ogallala aquifer than in Edwards aquifer (p<0.0001) regardless of interpolation methods. In regression analysis, the best models are when well depth and/or elevation were entered into the model as covariates regardless of area/aquifer or interpolation methods, and models with IDW are better than kriging in any area/aquifer. In conclusion, the accuracy in estimating groundwater arsenic level depends on both interpolation methods and wells' geographic distributions and characteristics in Texas. Taking well depth and elevation into regression analysis as covariates significantly increases the accuracy in estimating groundwater arsenic level in Texas with IDW in particular.
Asunto(s)
Arsénico/análisis , Monitoreo del Ambiente/métodos , Agua Subterránea/química , Contaminantes Químicos del Agua/análisis , Abastecimiento de Agua/análisis , Análisis de Regresión , TexasRESUMEN
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.
Asunto(s)
Trastornos del Conocimiento , Cognición/fisiología , Demencia , Enfermedades Vasculares , Anciano , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etnología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Demencia/diagnóstico , Demencia/etnología , Demencia/etiología , Demencia/fisiopatología , Función Ejecutiva , Femenino , Humanos , Pruebas de Inteligencia , Masculino , Americanos Mexicanos , Pruebas Neuropsicológicas , Pronóstico , Medición de Riesgo , Factores de Riesgo , Estados Unidos/epidemiología , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/etnología , Enfermedades Vasculares/psicología , Pesos y Medidas , Población BlancaRESUMEN
BACKGROUND: The aim was to examine the link between low-level arsenic exposure and cognitive functioning, and the potential role of a single nucleotide polymorphism (SNP A35991G, rs10748835) of the AS3MT gene in modifying this link. METHODS: Data were analyzed on 526 participants from Project FRONTIER. Hierarchical linear regressions were created with neuropsychological raw index scores as the outcome variable and arsenic exposure and AS3MT SNP as different predictor variables. RESULTS: Within the total sample, arsenic exposure was negatively associated with language (p < 0.001) and executive functioning (p < 0.001). Among those with the AA genotype of the AS3MT gene, arsenic levels were negatively associated with language (p < 0.001), attention (p = 0.01), and executive functioning (p = 0.04). Among those with the AG genotype, arsenic levels were positively associated with immediate (p = 0.04) and delayed memory (p < 0.001) and negatively associated with executive functioning (p = 0.03). Among those with the GG genotype, arsenic levels were negatively associated with visuospatial functioning (p = 0.02). CONCLUSIONS: Low-level arsenic exposure is associated with cognitive functioning; however, this association is modified by an AS3MT gene.
Asunto(s)
Arsénico/toxicidad , Cognición/efectos de los fármacos , Metiltransferasas/genética , Contaminantes Químicos del Agua/toxicidad , Adulto , Anciano , Anciano de 80 o más Años , Arsénico/análisis , Atención/efectos de los fármacos , Monitoreo del Ambiente , Función Ejecutiva/efectos de los fármacos , Humanos , Memoria/efectos de los fármacos , Persona de Mediana Edad , Pruebas Neuropsicológicas , Polimorfismo de Nucleótido Simple , Población Rural , Habla/efectos de los fármacos , Texas , Contaminantes Químicos del Agua/análisisRESUMEN
Treatment of Alzheimer's disease (AD) is significantly hampered by the lack of easily accessible biomarkers that can detect disease presence and predict disease risk reliably. Fluid biomarkers of AD currently provide indications of disease stage; however, they are not robust predictors of disease progression or treatment response, and most are measured in cerebrospinal fluid, which limits their applicability. With these aspects in mind, the aim of this article is to underscore the concerted efforts of the Blood-Based Biomarker Interest Group, an international working group of experts in the field. The points addressed include: (1) the major challenges in the development of blood-based biomarkers of AD, including patient heterogeneity, inclusion of the "right" control population, and the blood-brain barrier; (2) the need for a clear definition of the purpose of the individual markers (e.g., prognostic, diagnostic, or monitoring therapeutic efficacy); (3) a critical evaluation of the ongoing biomarker approaches; and (4) highlighting the need for standardization of preanalytical variables and analytical methodologies used by the field.
Asunto(s)
Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/diagnóstico , Biomarcadores/sangre , Progresión de la Enfermedad , HumanosRESUMEN
BACKGROUND: In people with genetic forms of Alzheimer's disease, such as in Down syndrome and autosomal-dominant Alzheimer's disease, pathological changes specific to Alzheimer's disease (ie, accumulation of amyloid and tau) occur in the brain at a young age, when comorbidities related to ageing are not present. Studies including these cohorts could, therefore, improve our understanding of the early pathogenesis of Alzheimer's disease and be useful when designing preventive interventions targeted at disease pathology or when planning clinical trials. We compared the magnitude, spatial extent, and temporal ordering of tau spread in people with Down syndrome and autosomal-dominant Alzheimer's disease. METHODS: In this cross-sectional observational study, we included participants (aged ≥25 years) from two cohort studies. First, we collected data from the Dominantly Inherited Alzheimer's Network studies (DIAN-OBS and DIAN-TU), which include carriers of autosomal-dominant Alzheimer's disease genetic mutations and non-carrier familial controls recruited in Australia, Europe, and the USA between 2008 and 2022. Second, we collected data from the Alzheimer Biomarkers Consortium-Down Syndrome study, which includes people with Down syndrome and sibling controls recruited from the UK and USA between 2015 and 2021. Controls from the two studies were combined into a single group of familial controls. All participants had completed structural MRI and tau PET (18F-flortaucipir) imaging. We applied Gaussian mixture modelling to identify regions of high tau PET burden and regions with the earliest changes in tau binding for each cohort separately. We estimated regional tau PET burden as a function of cortical amyloid burden for both cohorts. Finally, we compared the temporal pattern of tau PET burden relative to that of amyloid. FINDINGS: We included 137 people with Down syndrome (mean age 38·5 years [SD 8·2], 74 [54%] male, and 63 [46%] female), 49 individuals with autosomal-dominant Alzheimer's disease (mean age 43·9 years [11·2], 22 [45%] male, and 27 [55%] female), and 85 familial controls, pooled from across both studies (mean age 41·5 years [12·1], 28 [33%] male, and 57 [67%] female), who satisfied the PET quality-control procedure for tau-PET imaging processing. 134 (98%) people with Down syndrome, 44 (90%) with autosomal-dominant Alzheimer's disease, and 77 (91%) controls also completed an amyloid PET scan within 3 years of tau PET imaging. Spatially, tau PET burden was observed most frequently in subcortical and medial temporal regions in people with Down syndrome, and within the medial temporal lobe in people with autosomal-dominant Alzheimer's disease. Across the brain, people with Down syndrome had greater concentrations of tau for a given level of amyloid compared with people with autosomal-dominant Alzheimer's disease. Temporally, increases in tau were more strongly associated with increases in amyloid for people with Down syndrome compared with autosomal-dominant Alzheimer's disease. INTERPRETATION: Although the general progression of amyloid followed by tau is similar for people Down syndrome and people with autosomal-dominant Alzheimer's disease, we found subtle differences in the spatial distribution, timing, and magnitude of the tau burden between these two cohorts. These differences might have important implications; differences in the temporal pattern of tau accumulation might influence the timing of drug administration in clinical trials, whereas differences in the spatial pattern and magnitude of tau burden might affect disease progression. FUNDING: None.