RESUMO
Previous studies have indicated the potential of cerebrospinal fluid (CSF) α-synuclein (α-syn) to be an additional biomarker for improving differential diagnosis of Alzheimer's disease (AD). We evaluated α-syn diagnostic performance across a well-characterized patient cohort with long-term follow-up. For this purpose, CSF α-syn levels were determined in 25 subjects diagnosed with stable mild cognitive impairment (stable MCI; n = 25), 27 MCI cases due to AD (MCI-AD; n = 32), 24 MCI cases due to Lewy body disease (MCI-LBD; n = 24) and control subjects (Ctrl; n = 18). CSF α-syn levels discriminate between the four groups. There were higher α-syn levels in MCI-AD patients and lower levels in MCI-LBD patients. The combination of α-syn and P-tau resulted in a specificity of 99% and a sensitivity of 97% for MCI-AD. MCI-AD patients with early psychotic symptoms (n = 9) displayed a trend towards a decrease in P-tau and α-syn compared to the MCI-AD patients without psychotic symptoms (n = 23). We conclude that adding CSF α-syn to central core AD biomarkers improves an early differential diagnosis of MCI-AD from other forms of MCI. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
Assuntos
Doença de Alzheimer/complicações , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , alfa-Sinucleína/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Estudos Transversais , Diagnóstico Diferencial , Diagnóstico Precoce , Feminino , Humanos , Doença por Corpos de Lewy/diagnóstico , Masculino , Pessoa de Meia-Idade , Proteínas tau/líquido cefalorraquidianoRESUMO
BACKGROUND: Deficits in executive functions (EFs) are frequently detected in patients with Parkinson's disease (PD). The Frontal Assessment Battery (FAB) is a screening test for assessing EFs although it has not been so far adapted and validated in Spain. We evaluated the reliability and validity of the Spanish version of the FAB (FAB-E) in PD patients. MATERIALS AND METHODS: Our study included 54 healthy subjects and 67 PD patients. Cognitive assessment of participants was conducted using the FAB-E, Mini-Mental State Examination (MMSE), Trail Making Test (TMT), Revised-Barcelona Test (RBT) and Executive Interview (EXIT-25). Internal consistency, intra- and test-retest reliabilities, concurrent and discriminant validity of the FAB-E were examined. To evaluate the influence of cognitive dysfunction in PD on the performance of the FAB-E, we also classified the PD patients into groups according to their cognitive status as measured by the MMSE using published criteria to identify cognitive deficits in PD. RESULTS: The FAB-E showed good internal consistency (α = 0.751). The intraclass correlation coefficients (ranging from 0.559 to 0.891) and Spearman correlations (from 0.494 to 0.864) of the FAB-E subtests indicated a good-strong reliability. The total and subtest scores generally showed a good concurrent validity, except for the prehension behaviour item of the FAB-E and the Interference and Go/no-go tasks of the EXIT-25 that presented low estimates. Excluding the prehension behaviour subtest, the performance of the FAB-E was higher in the control group than in PD patients. Cognitive dysfunction in PD patients also indicated significant poorer FAB-E scores excepting the motor and prehension behaviour subtests. Discriminant analysis determined a cut-off of 14.5 was optimal to differentiate healthy subjects from PD patients. Moreover, a cut-off <12.5 allocated satisfactorily those PD patients with cognitive impairment (MMSE<26) and scores <11.5 classified suitably those PD patients with dementia (MMSE<24). CONCLUSION: The FAB-E is an accurate tool for evaluating EFs in patients with PD and can provide useful information for distinguishing PD patients with and without cognitive dysfunction at a bedside assessment.
Assuntos
Disfunção Cognitiva/diagnóstico , Função Executiva , Doença de Parkinson/psicologia , Idoso , Estudos de Casos e Controles , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Análise Discriminante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Reprodutibilidade dos Testes , EspanhaRESUMO
Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) are currently being assessed with two different assays. Our objective was to study if there is a correlation between values obtained by both techniques, to compare their validity and search for conversion factor between values obtained for every protein. We compared the performances of two commonly used platforms, an enzyme-linked immunosorbent assay (ELISA) and a multiplex (xMAP) technology for measurement of CSF Aß 1-42, total tau (T-tau), and phosphorylated tau 181 (P-tau 181p) proteins, in 30 AD patients and 28 control subjects. The relations between the variables of both techniques were evaluated using the Spearman p correlation coefficient (α = 0.05). Receiver operating characteristic and area under the curve (AUC) analyses were calculated for the variables of both techniques. The two assays platforms yielded different absolute values for the various analytes, always higher in ELISA. We found some correction factor between values: 2,1- to 3-fold for Aß 1-42; 4,1- to 4,6-fold for T-tau; and 1,4- to 1,6-fold for P-tau 181p. In addition, those values were highly correlated (Aß 1-42: r = 0.70, P < 0.01; T-tau: r = 0.90, P < 0.01; P-tau 181p: r = 0.85, P < 0.01) and the AUC for the variables showed very similar values. In conclusion, the results obtained with ELISA and xMAP platforms were highly correlated and its validity is very similar. Differences in absolute values point to the need for a clear description of the technique used. Moreover, we found some conversion factor between values of every protein that may be useful for transformation between both techniques.
Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Técnicas de Química Analítica/métodos , Idoso , Área Sob a Curva , Demografia , Feminino , Humanos , Masculino , Curva ROCRESUMO
Introducción. La demencia con cuerpos de Lewy (DCLW) es la más frecuente de las degenerativas, después de la enfermedad de Alzheimer. Objetivo. Analizar los biomarcadores core de la enfermedad de Alzheimer en el líquido cefalorraquídeo de pacientes exclusivamente hispanos con DCLW prodrómica, para conocer si existe alteración de la vía amiloide o de la vía tau. Pacientes y métodos. Entre 2008-2017 incluimos a 430 pacientes con deterioro cognitivo leve según los criterios de Petersen, procedentes de tres hospitales de la provincia de Alicante. Se les realizaron revisiones clínicas cada 6-12 meses para evaluar su estabilidad clínica o la progresión a demencia utilizando los criterios clínicos vigentes. Entre otras pruebas complementarias se analizaron los biomarcadores de enfermedad de Alzheimer en el líquido cefalorraquídeo. Resultados. Entre todos los pacientes incluidos, 26 desarrollaron DCLW y 29 se mantuvieron estables durante al menos cinco años, por lo que los consideramos como referencia. En este grupo solamente cinco (17%) tenían valores de proteína Abeta(1-42) inferiores a la normalidad, mientras que 16 (55%) de los pacientes con DCLW tenían niveles alterados. No se encontraron diferencias en los niveles de las proteínas tau. Al comparar los grupos con DCLW con y sin amiloidosis solamente encontramos diferencias en los niveles de proteína Abeta(1-42). Conclusiones. Destacamos la frecuente presencia de patología amiloidea en la DCLW prodrómica en nuestra población y la probable alteración de diferentes vías metabólicas en una misma demencia clínicamente definida
Introduction. Lewy body dementia (LBD) is the most frequent of the degenerative dementias, after Alzheimers disease. Aim. To analyse the core biomarkers of Alzheimers disease in the cerebrospinal fluid of exclusively Hispanic patients with prodromal LBD, in order to determine whether there is involvement of the amyloid pathway or the tau pathway. Patients and methods. Between 2008 and 2017 we included 430 patients with mild cognitive impairment according to Petersen criteria, from three hospitals in the province of Alicante. They underwent clinical check-ups every 6-12 months to evaluate their clinical stability or their progression to dementia using current clinical criteria. Among other complementary tests, biomarkers for Alzheimer's disease in the cerebrospinal fluid were analysed. Results. Of all the patients included, 26 developed LBD and 29 remained stable for at least five years, and were thus considered as a reference. In this group only five (17%) had Aβ1-42 protein values below normal, whereas 16 (55%) of the patients with LBD had altered levels. No differences were found in the levels of tau protein. On comparing the LBD groups with and without amyloidosis, differences were only found in the levels of Aβ1-42 protein. Conclusions. We highlight the frequent presence of amyloid pathology in prodromal LBD in our population, and the probable involvement of different metabolic pathways in the same clinically defined dementia
Assuntos
Humanos , Masculino , Feminino , Idoso , Doença por Corpos de Lewy/fisiopatologia , Doença de Alzheimer/fisiopatologia , Biomarcadores/líquido cefalorraquidiano , Estudos de Casos e Controles , Estudos RetrospectivosAssuntos
Isquemia Encefálica/etiologia , Doença de Fabry/complicações , Acidente Vascular Cerebral Lacunar/etiologia , Terapia de Reposição de Enzimas , Doença de Fabry/diagnóstico , Doença de Fabry/tratamento farmacológico , Doença de Fabry/genética , Doença de Fabry/urina , Paralisia Facial/etiologia , Globosídeos/urina , Humanos , Hipestesia/etiologia , Íntrons/genética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/etiologia , Neuroimagem , Recidiva , Deleção de Sequência , Triexosilceramidas/urina , alfa-Galactosidase/genética , alfa-Galactosidase/uso terapêuticoRESUMO
INTRODUCTION: Several studies have reported alterations in the cerebrospinal fluid biomarkers (Abeta-42, T-tau and P-tau proteins), both in Alzheimer's disease (AD) and in mild cognitive impairment (MCI). AIM: To perform a meta-analysis of the diagnostic yield of this technique for the prediction of patients with MCI who are going to progress to AD. MATERIALS AND METHODS: A search was conducted in PubMed and Embase of papers published between 1999 and September 2008, and as a result only prospective studies were included for the systematic review. The sensitivity and specificity for each biomarker were studied separately and also jointly. RESULTS: Of the 12 studies that were included, 6 quantified the Abeta-42 protein, 11 the T-tau protein and seven the P-tau protein. In three of the studies data was obtained from the three biomarkers in combination. The sensitivity of the quantification of the T-tau and P-tau proteins is 82%, with a diagnostic odds ratio of 12.09 (confidence interval 95%, CI 95% = 7.71-18.99; p = 0.1) and 16.29 (CI 95% = 9.69-27.4; p = 0.9), respectively. Alteration of any of the three biomarkers has a specificity of 87%, with a diagnostic odds ratio of 35.97 (CI 95% = 7.8-164.6; p = 0.04). CONCLUSIONS: The isolated alteration of T-tau or P-tau levels in cerebrospinal fluid is very sensitive for differentiating between patients with MCI who are going to develop AD and those who are going to remain stable. Normality of the three biomarkers is a very reliable way of ruling out the progression of AD in patients with MCI.
Assuntos
Doença de Alzheimer , Biomarcadores/líquido cefalorraquidiano , Transtornos Cognitivos/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Progressão da Doença , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , PubMed , Sensibilidade e Especificidade , Proteínas tau/líquido cefalorraquidianoRESUMO
No disponible