RESUMO
Urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) is regarded as a biomarker for ß-amyloid protein deposition in Alzheimer disease (AD). The value of AD7c-NTP in predicting post-stroke cognitive recovery was worth exploring. In total, 224 patients with first-ever stroke were enrolled in this retrospective study. Cognitive assessment was evaluated by Mini-Mental State Examination (MMSE), and cognitive improvement was defined as MMSE scores ≥27 or 4-score elevation at 3-month follow-up after stroke. The AD7c-NTP level was 0.68±0.40 ng/mL in the 135 patients with cognitive improvement, while the AD7c-NTP level was 1.49±0.99 ng/mL in the 89 patients without improvement ( P <0.001). Those displaying better cognitive recovery also had younger ages, higher MMSE scores, and lower NIHSS scores on admission. In multivariable logistic regression analysis, AD7c-NTP concentration (OR=9.14, 95% CI: 4.52-18.49, P <0.001), age (OR=1.04, 95% CI: 1.01-1.08, P =0.012), and NIHSS score on admission (OR=1.17, 95% CI: 1.07-1.28, P <0.001) remained the independent risk factors affecting cognitive recovery. The area under the receiver operating characteristics curve for AD7c-NTP in predicting unfavorable cognitive function was 0.80 (sensitivity: 0.73 and specificity: 0.84). Urinary AD7c-NTP is a valuable biomarker associated with post-stroke cognitive recovery. It might be adopted to discriminate coexisting AD pathology from vascular cognitive impairment.
Assuntos
Biomarcadores , AVC Isquêmico , Recuperação de Função Fisiológica , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Biomarcadores/urina , Recuperação de Função Fisiológica/fisiologia , Proteínas do Tecido Nervoso/urina , Cognição/fisiologia , Pessoa de Meia-Idade , Testes de Estado Mental e DemênciaRESUMO
Background: Urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) is a biomarker for the early diagnosis of Alzheimer's disease (AD). It remains unclear whether hepatorenal function affects the urinary AD7c-NTP level. Objective: To evaluate the effects of hepatorenal function on urinary AD7c-NTP level. Methods: We enrolled 453 participants aged 60-100 years. An automated chemistry analyzer was used to determine the indicators of serum hepatorenal function. Enzyme-linked immunosorbent assay was used to measure the urinary AD7c-NTP level. Results: Spearman's correlation analysis showed a negative correlation between urinary AD7c-NTP levels and indicators of hepatorenal function, including albumin (râ=â-0.181, pâ<â0.001), albumin/globulin ratio (râ=â-0.224, pâ<â0.001), cholinesterase (râ=â-0.094, pâ=â0.046), total carbon dioxide (râ=â-0.102, pâ=â0.030), and glomerular filtration rate (râ=â-0.260, pâ<â0.001), as well as a positive correlation with globulin (râ=â0.141, pâ=â0.003), aspartate transaminase (râ=â0.186, pâ<â0.001), blood urine nitrogen (râ=â0.210, pâ<â0.001), creatinine (râ=â0.202, pâ<â0.001), uric acid (râ=â0.229, pâ<â0.001), and cystatin C (râ=â0.265, pâ<â0.001). The least absolute shrinkage and selection operator (LASSO) regression analysis and multiple linear regression model analyses showed that the statistically significant hepatorenal indicators for predicting AD7c-NTP were A/G (pâ=â0.007), AST (pâ=â0.002), BUN (pâ=â0.019), and UA (pâ=â0.003). Conclusions: The effects of hepatorenal indicators should be considered when using urinary AD7c-NTP levels in clinical settings.
Assuntos
Doença de Alzheimer , Biomarcadores , Humanos , Feminino , Masculino , Idoso , Estudos Transversais , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Biomarcadores/urina , Biomarcadores/sangue , Doença de Alzheimer/urina , Doença de Alzheimer/diagnóstico , Cistatina C/sangue , Cistatina C/urina , China/epidemiologia , Proteínas do Tecido Nervoso/urina , Taxa de Filtração Glomerular/fisiologia , Povo Asiático , Rim/fisiopatologia , Testes de Função Hepática , População do Leste AsiáticoRESUMO
Background: Alzheimer-associated neuronal thread protein (AD7c-NTP) has been demonstrated to have high diagnostic accuracy in differentiating Alzheimer's disease (AD) patients from healthy individuals. However, it is yet unclear whether exercise can lower the level of AD7c-NTP in urine among active Korean elderly. Objective: To assess the effect of exercise on AD7c-ntp levels in urine and cognitive function among active Korean elderly. Methods: In total, 40 Korean elderly (≥65 years) were divided into Active Control group (CG, nâ=â10), Aerobic exercise group (AG, nâ=â18), and combined Resistance/Aerobic exercise group (RAG, nâ=â12). A total of 12 weeks of exercise intervention was implemented. At week 0 and 12, cognitive performance (Korean Mini-Mental State Examination, Korean-Color Word Stroop test), grip strength, and body composition (muscle mass and body fat percentage) were measured. Also, a morning urine sample was obtained from each subject. The level of AD7c-NTP was measured using competitive enzyme-linked immunosorbent assay (ELISA). Results: After 12 weeks of exercise intervention, there was a significant difference of AD7c-NTP levels between RAG and CG (pâ=â0.026), AG and CG (pâ=â0.032), respectively. Furthermore, the AD7c-NTP levels in urine showed negative correlation with K-MMSE scores (râ=â-0.390, pâ=â0.013) and grip strength (râ=â-0.376, pâ=â0.017), among all participants after exercise intervention. Conclusions: This is the first study to investigate urine biomarker through exercise intervention. In future stuides, participants who have low cognitive function and low activity levels need to be recruited to observe more significant 'Exercise' effect.
Assuntos
Cognição , Exercício Físico , Humanos , Masculino , Feminino , Idoso , Cognição/fisiologia , Exercício Físico/fisiologia , República da Coreia , Proteínas do Tecido Nervoso/urina , Terapia por Exercício/métodos , Doença de Alzheimer/urina , Doença de Alzheimer/diagnóstico , Biomarcadores/urina , Testes NeuropsicológicosRESUMO
BACKGROUND: Obstructive sleep apnea (OSA) is a multi-component disorder, which has many comorbidities, including cognitive impairment. Although its potential risk factors were unknown, they could affect the patient's quality of life and long-term prognosis. OBJECTIVE: The purpose of this study was to investigate the application of urinary Alzheimer's disease-associated neurofilament protein (AD7c-NTP) levels in the assessment of cognitive impairment in OSA patients, and to analyze the predictive value of potential high-risk factors on cognitive impairment in OSA patients. METHODS: 138 young and middle-aged adults were recruited and underwent overnight polysomnographic recording, Montreal Cognitive Assessment (MoCA), and urinary AD7c-NTP test. AD7c-NTP and other factors were further applied as biomarkers to develop a cognition risk prediction model. RESULTS: Compared with the control, OSA patients showed significantly lower MoCA scores and higher urinary AD7c-NTP concentrations, while the severe OSA group appeared more significant. The urinary AD7c-NTP level of the OSA cognitive impairment group was higher than that of the non-cognitive impairment group. The results of regression analysis showed that urinary AD7c-NTP level was an independent predictor of cognitive impairment in OSA patients. Based on urinary AD7c-NTP levels and other selected factors, a multimodal prediction model for assessing the risk of cognitive impairment in OSA patients was initially established. CONCLUSION: The increased urinary AD7c-NTP level could be used as a relevant peripheral biomarker of cognitive impairment in OSA patients. A model using urinary AD7c-NTP combined with other factors was developed and could accurately assess the cognition risk of OSA patients.
Assuntos
Disfunção Cognitiva , Proteínas do Tecido Nervoso , Apneia Obstrutiva do Sono , Humanos , Pessoa de Meia-Idade , Biomarcadores/urina , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/urina , Proteínas do Tecido Nervoso/urina , Qualidade de Vida , Apneia Obstrutiva do Sono/complicações , AdultoRESUMO
The AD7c-NTP is a promising biomarker for AD diagnosis. However, the exact urinary AD7c-NTP concentration to differentiate AD from the mild cognitive impairment (MCI) remains inconclusive. We enrolled 98 and 90 clinical defined AD and MCI patients, respectively, and access their cognition impairment with Neuropsychiatric Inventory (NPI) and Mental State Examination (MMSE) along with their urinary AD7c-NTP. We demonstrated that urinary AD7c-NTP level in sequence from high to low was AD, MCI, and healthy groups (P < .01), and the AD7c-NTP was positively and negatively correlated with the NPI and MMSE scores, respectively. Additionally, AD7c-NTP well-matched NPI subscale scores, including agitation, depression, and apathy (P < .05). Importantly, the optimal cut-off AD7c-NTP level to distinguish the AD and MCI was .94 ng/mL (sensitivity 85.71% & specificity 73.91%). Conclusively, urinary AD7c-NTP could be used for cognition impairment evaluation and differentiated diagnosis of AD and MCI.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Proteínas do Tecido Nervoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Doença de Alzheimer/urina , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/urina , Humanos , Proteínas do Tecido Nervoso/urina , Testes NeuropsicológicosRESUMO
We report an EN2-specific (Kd = 8.26 nM) aptamer, and a sensitive and specific enzyme-linked oligonucleotide assay (ELONA) for rapid and sensitive colorimetric detection of bladder and prostate cancer biomarker EN2 in urine. The assay relies on an aptamer-mediated hybridization chain reaction (HCR) to generate DNA nanostructures that bind to EN2 and simultaneously amplify signals. The assay can be performed within 2.5 h, and has a limit of detection of 0.34 nM in buffer and 2.69 nM in artificial urine. Moreover, this assay showed high specificity as it did not detect other urinary proteins, including biomarkers of other cancers. The proposed ELONA is inexpensive, highly reproducible, and has great chemical stability, so it may enable development of a simple, sensitive and accurate diagnostic tool to detect bladder and prostate cancers early.
Assuntos
Aptâmeros de Nucleotídeos , Neoplasias da Próstata , Anticorpos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Proteínas de Homeodomínio , Humanos , Masculino , Proteínas do Tecido Nervoso/urina , Oligonucleotídeos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/urina , Bexiga UrináriaRESUMO
OBJECTIVE: This study was performed to investigate the association between urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) with cerebral microbleeds (CMBs) based on the apolipoprotein E (APOE) genotypes. METHODS: A total of 471 patients with acute cerebral infarction screened by magnetic sensitive imaging were enrolled in this study. Among them, twenty-seven cases of mixed CMBs were excluded. A total of 444 patients were divided into two groups according to the presence or absence of CMBs: CMBs group (n = 92) and noncerebral microbleeds group (nCMBs) (n = 352). Urine AD7c-NTP levels were measured using a human enzyme immunoassay kit. RESULTS: In patients with lobar CMBs, there was an interaction between urine AD7c-NTP levels and APOE genotypes (p = 0.01). In patients with APOE ε3/ε3 allele, the odds ratio of lobar CMBs per standard deviation of urinary AD7c-NTP levels was 0.92 (95% CI: 0.70-1.19). In patients with APOE ε2+ or ε4+ allele, the multivariate-corrected odds ratio of lobar CMBs per standard deviation of urinary AD7c-NTP levels was 2.95 (95% CI: 1.38-6.27). CONCLUSION: A higher level of urinary AD7c-NTP is involved in lobar CMBs, not deep CMBs.
Assuntos
Doença de Alzheimer/patologia , Apolipoproteínas E/genética , Biomarcadores/urina , Hemorragia Cerebral/patologia , Imageamento por Ressonância Magnética/métodos , Proteínas do Tecido Nervoso/urina , Idoso , Doença de Alzheimer/genética , Doença de Alzheimer/urina , Hemorragia Cerebral/genética , Hemorragia Cerebral/urina , Testes Diagnósticos de Rotina , Feminino , Genótipo , Humanos , MasculinoRESUMO
BACKGROUND Accumulating evidence has shown that alpha-synuclein (alpha-syn) pathology is involved in the pathophysiology of Alzheimer's disease (AD). This study aimed to investigate the association between the levels of plasma alpha-syn protein, urinary Alzheimer-associated neuronal thread protein (AD7c-NTP), apolipoprotein epsilon 4 (ApoE ε4) alleles and cognitive decline in 60 AD patients compared with 28 age-matched normal controls (NCs) at a single center. MATERIAL AND METHODS All participants underwent alpha-syn, apolipoprotein E (ApoE), AD7c-NTP, cholesterol (CHO), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides (TGs) analyses, neuropsychological scale assessments and neuroimaging analysis. Moreover, urine and peripheral blood samples were collected from all participants. The levels of plasma alpha-syn and AD7c-NTP were assayed using an enzyme-linked immunosorbent assay (ELISA) kit. Other test results were obtained from China-Japan Friendship Hospital. RESULTS We found that plasma alpha-syn levels were significantly different between AD patients and NCs (p=0.045). alpha-Syn levels were also associated with AD7c-NTP (r=0.231, p=0.03) but not ApoE e4 (Z=-0.147, p=0.883) levels. Neither a-syn [CHO (p=0.432), HDL (p=0.484), LDL (p=0.733) or TGs (p=0.253)] nor AD7c-NTP [CHO (p=0.867), HDL (p=0.13), LDL (p=0.57) or TGs (p=0.678)] had a relationship with lipids. CONCLUSIONS This study showed that the levels of plasma alpha-syn protein and urinary AD7c-NTP were significantly increased in AD patients compared with NCs, but not with ApoE alleles or serum lipid levels.
Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Apolipoproteína E4/genética , Disfunção Cognitiva/fisiopatologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/urina , alfa-Sinucleína/genética , Idoso , Doença de Alzheimer/metabolismo , Apolipoproteína E4/sangue , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/genética , Feminino , Humanos , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , alfa-Sinucleína/sangueRESUMO
Urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) is elevated in early Alzheimer's disease (AD) and mild cognitive impairment, and is considered a biomarker for the early diagnosis of AD. However, it has not yet been investigated whether urinary AD7c-NTP is elevated with increases in blood biochemical indicators related to AD risk factors. We recruited 2180 participants, aged 35-93 years, from communities of four districts in Beijing. Blood biochemical indicators, including blood glucose, blood lipids, renal function, and high-sensitivity C-reactive protein, were measured using routine methods. Urinary AD7c-NTP was detected using an enzyme-linked immunosorbent assay AD7c-NTP kit. In the general population, there were no significant differences in urinary AD7c-NTP levels in subjects with different Mini-Mental State Examination levels or C-reactive protein values. After adjusting for age and sex, there were significant differences in urinary AD7c-NTP levels between different education levels, marital statuses, blood glucose, blood lipids, and kidney function. There was a negative correlation between urinary AD7c-NTP levels and serum creatinine (r = -0.128). There was a positive correlation between urinary AD7c-NTP levels and HbA1c (r = 0.104), insulin (r = 0.101), and triglycerides (r = 0.093). Urinary AD7c-NTP might be useful as a potential indicator to predict AD risk.
Assuntos
Proteínas do Tecido Nervoso/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We investigated the relationship between urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) levels and apolipoprotein epsilon 4 (ApoE É4) alleles, as well as other factors that cause cognitive decline, in the cognitively normal population. We recruited 329 cognitively normal right-handed Han Chinese subjects who completed ApoE gene testing and urinary AD7c-NTP testing. There was no significant difference in urinary AD7c-NTP levels between the normal control and subjective cognitive decline groups. Urinary AD7c-NTP levels were significantly higher in subjects with ApoE É3/4 and 4/4 [0.6074 (0.6541) ng/mL] than in subjects without ApoE É4 [0.4368 (0.3392) ng/mL and 0.5287 (0.3656) ng/mL], and urinary AD7c-NTP levels positively correlated with ApoE genotype grade (r = 0.165, p = 0.003). There were significant differences in urinary AD7c-NTP levels between subjects with and without a history of coronary heart disease or diabetes. Urinary AD7c-NTP levels were not related to years of education, nature of work, family history of dementia, a history of hypertension, stroke, anemia, or thyroid dysfunction. Urinary AD7c-NTP levels were positively correlated with ApoE grade in the cognitively normal population. The relationship between risk factors of cognitive decline and urinary AD7c-NTP levels provides a new way for us to understand AD and urinary AD7c-NTP.
Assuntos
Alelos , Apolipoproteína E4/genética , Cognição/fisiologia , Proteínas do Tecido Nervoso/urina , Idoso , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
BACKGROUND: Hypertension, a common chronic disease, is associated with cognitive impairment. Cognitive impairment, especially Alzheimer's disease (AD), seriously affects older adults' quality of life and aggravates the burden of disease on society and families. Elevated Alzheimer-associated neuronal thread protein (AD7c-NTP) has been observed in the urine of patients with AD and mild cognitive impairment; however, it is not clear whether this protein can be used as a biomarker for cognitive impairment in older hypertensive patients. OBJECTIVE: To explore the value of urinary AD7c-NTP, and the association of urinary AD7c-NTP with cognitive function in older hypertensive patients. METHODS: This was a cross-sectional study. In total, 134 hypertensive patients aged ≥60 years were divided into two groups: Lower Cognitive Function group (LCF group, nâ=â89) and Normal Control group (NC group, nâ=â45) based on the Montreal Cognitive Assessment (MoCA). Urinary AD7c-NTP, blood glucose, serum insulin, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured. RESULTS: Urinary AD7c-NTP level was significantly higher in the LCF group than in the NC group [0.48 (0.21-1.00) versus 0.25 (0.04-0.44) ng/ml, pâ<â0.001]. The LCF group had lower SOD level [(43.07±23.74) versus (53.12±25.80) U/ml, pâ=â0.026] and higher homeostasis model assessment of insulin resistance (HOMA-IR) [7.17 (3.74-13.94) versus 6.01 (3.78-7.43), p = 0.033] than the NC group. Urinary AD7c-NTP level was associated with MoCA score and HOMA-IR but not with SOD, MDA, blood glucose, and insulin. CONCLUSION: The level of urinary AD7c-NTP is elevated in older hypertensive patients with lower cognitive function, and insulin resistance may be involved in the process.
Assuntos
Transtornos Cognitivos/urina , Hipertensão/urina , Proteínas do Tecido Nervoso/urina , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Glicemia/análise , Transtornos Cognitivos/psicologia , Disfunção Cognitiva/psicologia , Disfunção Cognitiva/urina , Estudos Transversais , Feminino , Humanos , Hipertensão/psicologia , Resistência à Insulina , Masculino , Malondialdeído/análise , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Superóxido Dismutase-1/urinaRESUMO
Purpose: Prostate-specific antigen (PSA) is a sensitive but unspecific marker for prostate cancer (PC) detection, which may result in harms including overdiagnosis and overtreatment. Therefore, the development of new markers is of absolute value. The urinary level of engrailed-2 (EN2) protein has been recently suggested as a promising PC biomarker, correlating with tumour volume and stage. This study evaluated EN2 and its potential use in clinical practice.Materials and methods: Urinary EN2 was assessed by different commercially available enzyme-linked immunosorbent assay kits. The study sample included 90 patients with clinically localized PC compared to 30 healthy controls, and a group of 40 patients indicated for prostate biopsy due to an elevated PSA level where both pre- and post-digital rectal examination urine samples were collected.Results: No statistical difference between the patient group and the control group was obtained in all measured variables. There was no significant correlation between urinary EN2 and serum PSA, tumour staging and grading. Attentive DRE did not lead to significant changes of urinary EN2 or impact on its predictive power.Conclusions: Our results show that EN2 as a PC biomarker brings no additional value to the current use of PSA in clinical practice.
Assuntos
Biomarcadores Tumorais/urina , Proteínas de Homeodomínio/urina , Proteínas do Tecido Nervoso/urina , Neoplasias da Próstata/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/sangue , Biópsia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/urina , Carga Tumoral , UrináliseRESUMO
Urinary Alzheimer-associated neural thread protein (AD7c-NTP) is a potential biomarker of Alzheimer disease (AD) or mild cognitive impairment (MCI). It is still unclear whether the urinary levels of AD7c-NTP are different between patients with amnestic MCI (aMCI) and nonamnestic MCI (naMCI). The present study aimed to explore the differences in urinary levels of AD7c-NTP between patients with aMCI and naMCI. Forty-six patients with MCI were divided into aMCI group (n = 23) and naMCI group (n = 23). The mean level of urinary AD7c-NTP in the aMCI group (32.75 ± 10.0 µg/mL) was significantly higher than that in the naMCI group (25.34 ± 9.0 µg/mL; P = .011). As far as we know, the present study is the first to show that individuals with aMCI have higher levels of urinary AD7c-NTP than those with naMCI, suggesting that urinary AD7c-NTP may be a potential biomarker to help identify patients with aMCI and naMCI.
Assuntos
Amnésia/urina , Biomarcadores/urina , Disfunção Cognitiva/urina , Proteínas do Tecido Nervoso/urina , Idoso , Feminino , Humanos , Masculino , Testes Neuropsicológicos/estatística & dados numéricosRESUMO
Subjective cognitive decline (SCD) is a risk factor for Alzheimer's disease (AD). Urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) has been identified as a biomarker for AD. It was hypothesized that if urinary AD7c-NTP were also elevated in SCD, as it is in prodromal AD (mild cognitive impairment stage), it could be a convenient and efficient clinical biomarker for the early diagnosis of SCD. SCD is often accompanied by a depressive state (DS), and the impact of DS on urinary AD7c-NTP levels remains unknown. A total of 297 right-handed Chinese Han subjects were recruited, including 98 subjects with SCD, 92 patients with DS, and 107 well-matched cognitively normal controls (NC). The levels of AD7c-NTP in urine samples were measured using an enzyme-linked immunosorbent assay AD7c-NTP kit. Our results demonstrated that urinary AD7c-NTP levels in the SCD group (0.7561±0.5657âng/mL) were not significantly higher than in either the DS (0.7527±0.5607âng/mL) or NC (0.7214±0.5077âng/mL) groups. Furthermore, urinary AD7c-NTP levels were not correlated with Hamilton Depression Rating Scale and Hamilton Anxiety Scale scores, but they were negatively associated with Mini-Mental State Examination scores (râ=â-0.222, pâ=â0.033) and Montreal Cognitive Assessment-Basic scores (râ=â-0.207, pâ=â0.048). Urinary AD7c-NTP level is not elevated in SCD and is unaffected by DS. Urinary AD7c-NTP may therefore not be a good potential biomarker for SCD and DS, although it may become elevated with more severe cognitive decline.
Assuntos
Doença de Alzheimer/diagnóstico , Disfunção Cognitiva , Depressão , Proteínas do Tecido Nervoso/urina , Idoso , Biomarcadores/urina , China , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Disfunção Cognitiva/urina , Depressão/diagnóstico , Depressão/psicologia , Depressão/urina , Autoavaliação Diagnóstica , Diagnóstico Precoce , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Testes NeuropsicológicosRESUMO
BACKGROUND: Alzheimer's disease has become a public health crisis globally due to its increasing incidence. The purpose of this study was to establish an early warning model using artificial neural network (ANN) for early diagnosis of AD and to explore early sensitive markers for AD. METHODS: A population based nested case-control study design was used. 89 new AD cases with good compliance who were willing to provide urine and blood specimen were selected from the cohort of 2482 community-dwelling elderly aged 60 years and over from 2013 to 2016. For each case, two controls living nearby were identified. Biomarkers for AD in urine and blood, neuropsychological functions and epidemiological parameters were included to analyze potential risk factors of AD. Compared with logistic regression, k-Nearest Neighbor (kNN) and support vector machine (SVM) model, back-propagation neural network of three-layer topology structures was applied to develop the early warning model. The performance of all models were measured by sensitivity, specificity, accuracy, positive prognostic value (PPV), negative prognostic value (NPV), the area under curve (AUC), and were validated using bootstrap resampling. RESULTS: The average age of AD group was about 5 years older than the non-AD controls (P < 0.001). Patients with AD included a significantly larger proportion of subjects with family history of dementia, compared with non-AD group. After adjusting for age and gender, the concentrations of urinary AD7c-NTP and aluminum in blood were significantly higher in AD group than non-AD group (2.01 ± 1.06 vs 1.03 ± 0.43, 1.74 ± 0.62 vs 1.24 ± 0.41 respectively), but the concentration of Selenium in AD group (2.26 ± 0.59) was significantly lower than that in non-AD group (2.61 ± 1.07). All the models were established using 18 variables that were significantly different between AD patients and controls as independent variables. The ANN model outperformed the other classifiers. The AUC for this ANN was 0.897 and the model obtained the accuracy of 92.13%, the sensitivity of 87.28% and the specificity of 94.74% on the average. CONCLUSIONS: Increased risk of AD may be associated with higher age among senior citizens in urban communities. Urinary AD7c-NTP is clinically valuable for the early diagnosis. The established ANN model obtained a high accuracy and diagnostic efficiency, which could be a low-cost practicable tool for the screening and diagnosis of AD for citizens.
Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/sangue , Proteínas do Tecido Nervoso/urina , Redes Neurais de Computação , Fragmentos de Peptídeos/sangue , Oligoelementos/sangue , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Área Sob a Curva , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Diagnóstico Precoce , Feminino , Humanos , Masculino , Sensibilidade e EspecificidadeRESUMO
Accumulation of tau protein is associated with both Alzheimer's disease (AD) and late-life depression (LLD). Alzheimer-associated neuronal thread protein (AD7c-NTP), which is closely linked with the tau protein, is elevated in the cerebrospinal fluid and urine of AD patients. This study examined the association between urinary AD7c-NTP and late-life depression with cognitive impairment. One hundred and thirty-eight subjects were recruited into late-life depression with cognitive impairment (LLD-CI, n=52), late-life depression without cognitive impairment (LLD-NCI, n=29), AD (n=27), and healthy control (HC, n=30) groups. The level of urinary AD7c-NTP was measured using the enzyme-linked immunosorbent assay method. The Montreal Cognitive Assessment scale (MoCA), Hamilton Rating Scale for Depression (HRSD) and Hamilton Anxiety Rating Scale (HAMA) were used to assess cognitive functions and depressive and anxiety symptoms in the AD and LLD groups. Urinary levels of AD7c-NTP in the LLD-CI group (1.0±0.7ng/ml) were significantly higher than both the LLD-NCI (0.5±0.3ng/ml) and HC groups (0.5±0.3ng/ml), but lower than in the AD group (1.6±1.7 ng/ml). No significant associations were found in the level of urinary AD7c-NTP in relation to age, gender, education and MoCA in the LLD-CI group. The level of urinary AD7c-NTP appears to be associated with cognitive impairment in late-life depression and may be a potential biomarker for early identification of cognitive impairment in LLD.
Assuntos
Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/urina , Depressão/fisiopatologia , Depressão/urina , Proteínas do Tecido Nervoso/urina , Biomarcadores/urina , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Projetos PilotoRESUMO
BACKGROUND: Alzheimer-associated neuronal thread protein (AD7c-NTP) has been found to be a biomarker for Alzheimer's disease (AD). OBJECTIVE: The aim of the present study was to investigate the distribution of Alzheimer-associated neuronal thread protein and its relationship to common chronic diseases in the general population. METHODS: Urine samples of 1,805 participants were collected from four districts (Xi Cheng, Fang Shan, Tong Zhou, and Yan Qing) in Beijing. The assessment in this study included a questionnaire that captured participants' demographic information, use of medication and histories of disease, neurological examinations, psychometric evaluations, physical and clinical examinations, and laboratory tests. RESULTS: Urine AD7c-NTP level was increased among the population over 60 years old and females exhibited higher levels than males. These results controlled for other demographic factors such as education levels, employment status, body mass index and current residence. The urine AD7c-NTP levels exhibited no association with non-neurological diseases (0.3346±0.4482 ng/ml), such as hypertension (0.3445±0.4187), stroke (0.3652±0.4010), diabetes (0.3319±0.4371), dyslipidemia (0.3440±0.4314), renal insufficiency (0.3223±0.3909), cancer (0.5055±1.0006), chronic lung disease (0.2911±0.2852), chronic liver disease (0.5579±0.6726), severe depression symptoms (0.5186±0.7040), and mild depression symptoms (0.3669±0.3811). CONCLUSIONS: Cut-off values for urine AD7c-NTP levels for different age groups and genders should be established. AD7c-NTP levels proved relatively stable in the body and were not impacted by demographic factors or common chronic diseases.
Assuntos
Doença Crônica/epidemiologia , Proteínas do Tecido Nervoso/urina , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/urina , Biomarcadores/sangue , Biomarcadores/urina , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Fatores SocioeconômicosRESUMO
BACKGROUND: Alzheimer-associated neuronal thread protein (AD7c-NTP) has been found to be a candidate biomarker of Alzheimer's disease (AD). OBJECTIVE: To investigate the effects of urine collected time, different preservatives addition, and storage condition on the measurement of urine AD7c-NTP by enzyme-linked immunosorbent assay (ELISA). METHODS: Three hundred urine samples were collected from 20 participants at three time points on five consecutive days. These samples were immediately placed at 4°C and detected within 2âh. The single spot samples of the first day morning were split into eleven duplicate aliquots (a-k) of 1âml each, (a) without any preservative (untreated), (b) containing boric acid (2âg/L), (c) containing NaHCO3 (5âg/L), (a-c) were detected at six different time points. For the other eight preservative-free samples, (d-g) were stored at -20°C and (h-k) were stored at -70°C, respectively, detected at different time points. All of the results were compared with the baseline urine. RESULTS: The urine AD7c-NTP levels at different time points behaved stably (pâ>â0.05). Urine samples without any preservative increased over time, and compared with the NaHCO3 addition group, boric acid addition group behaved stably. Samples stored at -20°C and -70°C led to an obviously false positive. CONCLUSIONS: AD7c-NTP can be tested using random urine instead of the first morning urine. If the specimen cannot be tested in time, boric acid appears to be an acceptable preservative with storage at 4°C, freezing is not recommended.
Assuntos
Doença de Alzheimer/urina , Ensaio de Imunoadsorção Enzimática/métodos , Proteínas do Tecido Nervoso/urina , Adulto , Ritmo Circadiano , Feminino , Voluntários Saudáveis , Humanos , Fatores de Tempo , Adulto JovemRESUMO
INTRODUCTION: Prostate cancer is the second type of cancer diagnosed and the fifth cause of death in men worldwide. Early diagnosis helps to control disease progression. Currently, prostate specific antigen is the standard biomarker, as it has a broad scope of identification and, thus, new and more specific biomarkers must be studied. OBJECTIVE: To evaluate the accuracy of engrailed-2 protein (EN2) in urine as a prostate cancer biomarker. METHOD: A comprehensive search was conducted in the period from January 2005 to July 2016 using the following electronic databases: Medline (PubMed), Embase, Cochrane Library and Lilacs. The keywords used in the databases were: "engrailed-2," "EN2," "prostatic neoplasms." The search was limited to humans and there was no language restriction. Critical appraisal of the included studies was performed according to Quadas-2. Statistical analysis was performed using Meta-DiSc® and RevMan 5.3 softwares. RESULTS: A total of 248 studies were identified. After title and abstract screening, 231 studies were removed. A total of 17 studies were read in full and two studies were included in the meta-analysis. The pooled sensitivity was 66% (95CI 0.56-0.75) and specificity was 89% (95CI 0.86-0.92). The DOR was 15.08 (95CI 8.43-26.97). CONCLUSION: The EN2 test showed high specificity (89%) and low sensitivity (66%).
Assuntos
Proteínas de Homeodomínio/urina , Proteínas do Tecido Nervoso/urina , Neoplasias da Próstata/diagnóstico , Biomarcadores Tumorais/urina , Progressão da Doença , Humanos , Masculino , Valor Preditivo dos Testes , Antígeno Prostático Específico/sangue , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Expression of neuronal thread protein (NTP), which is considered to be related to neuritic sprouting and neuronal death, may be elevated in brain tissue, cerebrospinal fluid, and even urine in patients with Alzheimer's disease (AD). OBJECTIVE: In this study, we analyzed the correlation between urine AD-associated NTP (AD7c-NTP) level, and amyloid-ß (Aß) deposition, and clinical symptoms in AD and mild cognitive impairment (MCI). METHODS: Twenty-two patients with mild to moderate AD and 8 subjects with MCI were recruited. Aß deposition was measured with [11C]-labeled Pittsburgh compound B (PiB)-positron emission tomography (PET) in all participants. Urine AD7c-NTP levels were measured using enzyme-linked immunosorbent assay. Mini-Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI) were used to evaluate cognitive function and behavioral psychological symptoms, respectively. RESULTS: Fourteen (63.6%) of AD patients and 2 (25.0%) of MCI subjects were Aß positive on PiB-PET. There was a significant difference in urine AD7c-NTP level between Aß positive (2.27±2.22âng/ml) and negative (0.55±0.60âng/ml) subjects (pâ=â0.018). Using 1.46âng/ml as a cut-off value, 68.8% of Aß positive subjects showed elevated urine AD7c-NTP level, and 92.9% of Aß negative subjects showed normal urine AD7c-NTP level. There were no relationships between urine AD7c-NTP level and MMSE and total NPI scores. However, AD7c-NTP level positively correlated with agitation score on NPI. CONCLUSIONS: Urine AD7c-NTP had high specificity and moderate sensitivity in predicting Aß deposition among patients with cognitive impairment. Furthermore, urine AD7c-NTP level strongly correlated with the symptom of agitation.