Aportación del cociente ABeta1-42/ABeta1-40 al concepto enfermedad de Alzheimer contribuye al deterioro cognitivo leve / Role of the ABeta1-42/ABeta1-40 ratio in the concept Alzheimers disease contributes to mild cognitive impairment

Introducción: La demostración de amiloidosis cerebral, mediante la alteración de los niveles del péptido Aß1-42 o del cociente Aß1-42/Aß1-40, es condición necesaria para aceptar la presencia de la enfermedad de Alzheimer (EA), según los criterios de 2018 del National Institute on Aging y la Alzheimers Association (NIA-AA 2018). Objetivo: Calcular la ganancia diagnóstica que supone el cálculo del cociente Aß1-42/Aß1-40 respecto al uso exclusivo de los niveles del péptido Aß42 para identificar a los pacientes que pertenecen al grupo EA contribuye al deterioro cognitivo leve (DCL), según los criterios NIA-AA 2018. Pacientes y métodos: Entre abril de 2018 y abril de 2020, incluimos a 62 pacientes con DCL, según los criterios de Petersen de 2006, a los que se les realizó una punción lumbar dentro del proceso diagnóstico. El líquido cefalorraquídeo se analizó mediante la metodología inmunoquimioluminiscente, que permite cuantificar los biomarcadores core de la EA en el líquido cefalorraquídeo y el péptido Aß1-40. Resultados: Cuarenta y dos pacientes (67,7%) presentaron criterios de EA contribuye a DCL. La utilización del cociente Aß1-42/Aß1-40, respecto a la utilización exclusiva de los niveles de Aß1-42, supone una ganancia diagnóstica del 19% (ocho pacientes) para establecer la presencia de amiloidosis en el líquido cefalorraquídeo de estos pacientes. Conclusión: El cálculo del cociente Aß1-42/Aß1-40 supone una ganancia diagnóstica clara para identificar a los pacientes que pertenecen al grupo EA contribuye al DCL’, por lo que aconsejamos su utilización, como se viene recogiendo en la bibliografía más reciente. En nuestro conocimiento, es la primera publicación de estas características en lengua española.(AU)

Introduction: Evidence of cerebral amyloidosis, by altered levels of the peptide Aβ1-42 or the Aβ1-42/Aβ1-40 ratio, is a necessary condition to accept the presence of Alzheimer’s disease (AD), according to the 2018 criteria of the National Institute on Aging and Alzheimer’s Association (NIA-AA 2018). Aim: To calculate the diagnostic gain obtained from calculating the Aβ1-42/Aβ1-40 ratio with respect to the exclusive use of the peptide Aβ42 to identify patients belonging to the ‘Alzheimer’s disease contributes to mild cognitive impairment (MCI)’ group, according to NIA-AA 2018 criteria. Patients and methods: Between April 2018 and April 2020, we included 62 patients with MCI, according to Petersen’s 2006 criteria, who underwent lumbar puncture as part of the diagnostic process. Cerebrospinal fluid was analysed using the immunochemiluminescence methodology, which makes it possible to quantify core AD biomarkers in cerebrospinal fluid and the peptide Aβ1-40. Results: Forty-two patients (67.7%) presented criteria supporting ‘AD contributes to MCI’. The use of the Aβ1-42/Aβ1-40 ratio, compared to the exclusive use of Aβ1-42 levels, represents a diagnostic gain of 19% (eight patients) to establish the presence of amyloidosis in the cerebrospinal fluid of these patients. Conclusion: The calculation of the Aβ1-42/Aβ1-40 ratio is a clear diagnostic gain for identifying patients belonging to the ‘AD contributes to MCI’ group, and we therefore recommend its use, as reported in the most recent literature. To our knowledge, this is the first publication of its kind in Spanish.(AU)

[Role of the Aß1-42/Aß1-40 ratio in the concept 'Alzheimer's disease contributes to mild cognitive impairment']. / Aportación del cociente Aß1-42/Aß1-40 al concepto 'enfermedad de Alzheimer contribuye al deterioro cognitivo leve'.

INTRODUCTION: Evidence of cerebral amyloidosis, by altered levels of the peptide Aß1-42 or the Aß1-42/Aß1-40 ratio, is a necessary condition to accept the presence of Alzheimer's disease (AD), according to the 2018 criteria of the National Institute on Aging and Alzheimer's Association (NIA-AA 2018). AIM: To calculate the diagnostic gain obtained from calculating the Aß1-42/Aß1-40 ratio with respect to the exclusive use of the peptide Aß42 to identify patients belonging to the 'Alzheimer's disease contributes to mild cognitive impairment (MCI)' group, according to NIA-AA 2018 criteria. PATIENTS AND METHODS: Between April 2018 and April 2020, we included 62 patients with MCI, according to Petersen's 2006 criteria, who underwent lumbar puncture as part of the diagnostic process. Cerebrospinal fluid was analysed using the immunochemiluminescence methodology, which makes it possible to quantify core AD biomarkers in cerebrospinal fluid and the peptide Aß1-40. RESULTS: Forty-two patients (67.7%) presented criteria supporting 'AD contributes to MCI'. The use of the Aß1-42/Aß1-40 ratio, compared to the exclusive use of Aß1-42 levels, represents a diagnostic gain of 19% (eight patients) to establish the presence of amyloidosis in the cerebrospinal fluid of these patients. CONCLUSION: The calculation of the Aß1-42/Aß1-40 ratio is a clear diagnostic gain for identifying patients belonging to the 'AD contributes to MCI' group, and we therefore recommend its use, as reported in the most recent literature. To our knowledge, this is the first publication of its kind in Spanish.

TITLE: Aportación del cociente Aß1-42/Aß1-40 al concepto 'enfermedad de Alzheimer contribuye al deterioro cognitivo leve'.Introducción. La demostración de amiloidosis cerebral, mediante la alteración de los niveles del péptido Aß1-42 o del cociente Aß1-42/Aß1-40, es condición necesaria para aceptar la presencia de la enfermedad de Alzheimer (EA), según los criterios de 2018 del National Institute on Aging y la Alzheimer's Association (NIA-AA 2018). Objetivo. Calcular la ganancia diagnóstica que supone el cálculo del cociente Aß1-42/Aß1-40 respecto al uso exclusivo de los niveles del péptido Aß42 para identificar a los pacientes que pertenecen al grupo 'EA contribuye al deterioro cognitivo leve (DCL)', según los criterios NIA-AA 2018. Pacientes y métodos. Entre abril de 2018 y abril de 2020, incluimos a 62 pacientes con DCL, según los criterios de Petersen de 2006, a los que se les realizó una punción lumbar dentro del proceso diagnóstico. El líquido cefalorraquídeo se analizó mediante la metodología inmunoquimioluminiscente, que permite cuantificar los biomarcadores core de la EA en el líquido cefalorraquídeo y el péptido Aß1-40. Resultados. Cuarenta y dos pacientes (67,7%) presentaron criterios de 'EA contribuye a DCL'. La utilización del cociente Aß1-42/Aß1-40, respecto a la utilización exclusiva de los niveles de Aß1-42, supone una ganancia diagnóstica del 19% (ocho pacientes) para establecer la presencia de amiloidosis en el líquido cefalorraquídeo de estos pacientes. Conclusión. El cálculo del cociente Aß1-42/Aß1-40 supone una ganancia diagnóstica clara para identificar a los pacientes que pertenecen al grupo 'EA contribuye al DCL', por lo que aconsejamos su utilización, como se viene recogiendo en la bibliografía más reciente. En nuestro conocimiento, es la primera publicación de estas características en lengua española.

[Frequent involvement of the amyloid pathway in prodromal dementia with Lewy bodies]. / Frecuente alteracion de la via amiloide en la demencia con cuerpos de Lewy prodromica.

INTRODUCTION: Lewy body dementia (LBD) is the most frequent of the degenerative dementias, after Alzheimer's disease. AIM: To analyse the core biomarkers of Alzheimer's 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 Abeta(1-42) 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 Abeta(1-42) 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.

TITLE: Frecuente alteracion de la via amiloide en la demencia con cuerpos de Lewy prodromica.Introduccion. La demencia con cuerpos de Lewy (DCLW) es la mas frecuente de las degenerativas, despues de la enfermedad de Alzheimer. Objetivo. Analizar los biomarcadores core de la enfermedad de Alzheimer en el liquido cefalorraquideo de pacientes exclusivamente hispanos con DCLW prodromica, para conocer si existe alteracion de la via amiloide o de la via tau. Pacientes y metodos. Entre 2008-2017 incluimos a 430 pacientes con deterioro cognitivo leve segun los criterios de Petersen, procedentes de tres hospitales de la provincia de Alicante. Se les realizaron revisiones clinicas cada 6-12 meses para evaluar su estabilidad clinica o la progresion a demencia utilizando los criterios clinicos vigentes. Entre otras pruebas complementarias se analizaron los biomarcadores de enfermedad de Alzheimer en el liquido cefalorraquideo. 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%) tenian valores de proteina Abeta(1-42) inferiores a la normalidad, mientras que 16 (55%) de los pacientes con DCLW tenian niveles alterados. No se encontraron diferencias en los niveles de las proteinas tau. Al comparar los grupos con DCLW con y sin amiloidosis solamente encontramos diferencias en los niveles de proteina Abeta(1-42). Conclusiones. Destacamos la frecuente presencia de patologia amiloidea en la DCLW prodromica en nuestra poblacion y la probable alteracion de diferentes vias metabolicas en una misma demencia clinicamente definida.

Diagnostic Validity Comparison Between Criteria Based on CSF Alzheimer's Disease Biomarkers.

AIM: To compare the diagnostic validity of NIA-AA criteria, for AD CSF biomarkers, with our own new criteria. MATERIALS AND METHODS: Between 2008 and 2011, 170 patients with Mild Cognitive Impairment (MCI) were included. CSF levels of Aß1-42, T-tau, P-tau181, and ratios of T-tau/Aß1-42 and P-tau181/Aß1-42 were analyzed. In our criteria, we considered 3 or more abnormal variables indicative of a high likelihood of MCI due to AD. RESULTS: After a clinical follow-up of 4.5 ± 1.2 years, 44 patients remained stable, 95 developed AD, 15 other forms of dementia, 7 died and 9 received other diagnoses. Using the NIA-AA criteria and our own criteria, the diagnostic validity of the CSF biomarkers was 58% versus 85%, specificity 84% versus 72%, PPV 82% versus 79% and NPV 61% versus 79%. CONCLUSION: The inclusion of the ratios in diagnostic criteria increases sensitivity and NPV for the diagnosis of MCI due to AD.

Influence of APOE Genotype on Alzheimer's Disease CSF Biomarkers in a Spanish Population.

OBJECTIVES: To evaluate the association between apolipoprotein E (APOE) genotype and cerebrospinal fluid (CSF) levels of Alzheimer's disease (AD) biomarkers and to study the influence of APOE genotype on the development of AD in a Spanish population. MATERIAL AND METHODS: The study comprised 29 amnestic mild cognitive impairment (MCI) patients and 27 control subjects. Using ELISA methodology, CSF biomarkers and tau/Aß ratios were obtained. ANOVA and adjusted odds ratios were calculated. RESULTS: We observed the effect of APOE genotype and age on CSF AD variables. The progression to AD was more clearly influenced by CSF AD variables than by age or APOE status. CONCLUSIONS: APOE status influences CSF AD variables. However, the presence of APOE ε4 does not appear to be a deterministic factor for the development of AD, because CSF variables have a greater influence on progression to the disease. These results confirm previous observations and, to our knowledge, are the first published in a Spanish population.

A comparison of early diagnostic utility of Alzheimer disease biomarkers in brain magnetic resonance and cerebrospinal fluid.

INTRODUCTION: The goals of this study were to compare the early diagnostic utility of Alzheimer disease biomarkers in the CSF with those in brain MRI in conditions found in our clinical practice, and to ascertain the diagnostic accuracy of both techniques used together. METHODS: Between 2008 and 2009, we included 30 patients with mild cognitive impairment (MCI) who were examined using 1.5 Tesla brain MRI and AD biomarker analysis in CSF. MRI studies were evaluated by 2 radiologists according to the Korf́s visual scale. CSF biomarkers were analysed using INNOTEST reagents for Aß1-42, total-tau and phospho-tau181p. We evaluated clinical changes 2 years after inclusion. RESULTS: By 2 years after inclusion, 15 of the original 30 patients (50%) had developed AD (NINCDS-ADRA criteria). The predictive utility of AD biomarkers in CSF (RR 2.7; 95% CI, 1.1-6.7; P<.01) was greater than that of MRI (RR 1.5; 95% CI 95%, 0.7-3.4; P<.2); using both techniques together yielded a sensitivity and a negative predictive value of 100%. Normal results on both complementary tests ruled out progression to AD (100%) within 2 years of inclusion. CONCLUSIONS: Our results show that the diagnostic accuracy of biomarkers in CSF is higher than that of biomarkers in MRI. Combined use of both techniques is highly accurate for either early diagnosis or exclusion of AD in patients with MCI.

Mechanisms and treatment of cancer cachexia.

According to a recent consensus, cachexia is a complex metabolic syndrome associated with underlying illness and characterised by loss of muscle with or without loss of fat mass. The prominent clinical feature of cachexia is weight loss. Cachexia occurs in the majority of terminal cancer patients and it is responsible for the deaths of 22% of cancer patients. Although body weight is, indeed, an important factor to be taken into consideration in any cachexia treatment, body composition, physical performance and quality of life should be monitored. From the results presented here, one can speculate that a single therapy may not be completely successful in the treatment of cachexia. From this point of view, treatments involving different combinations are more likely to be successful. The objectives of any therapeutical combination are two: an anticatabolic aim directed towards both fat and muscle catabolism and an anabolic objective leading to the synthesis of macromolecules such as contractile proteins.

Pacientes con deterioro cognitivo leve y reducción de la proteína Aβ 1-42 en LCR evolucionan rápidamente a enfermedad de Alzheimer / Patients with mild cognitive impairment and a reduced CSF A_1-42 protein progress rapidly to Alzheimer’s disease

Introducción: En muchos artículos recientes, el análisis de las proteínas Aβ 1-42, tau total (T-tau) y tau fostorilada (P-tau) en LCR puede discriminar entre los pacientes con deterioro cognitivo leve (DCL) estables y aquellos otros que van a progresar a enfermedad de Alzheimer (EA). Nuestro objetivo fue comprobar la capacidad de estas proteínas del LCR para discriminar, entre nuestros pacientes DCL, según la evolución clínica en el año siguiente a la punción lumbar. Material y métodos: Se incluyó a 36 pacientes DCL amnésico (criterios de Petersen 2006) procedentes de la consulta de deterioro cognitivo del Hospital General de Alicante. Usando los reactivos INNO-BIA Alzbio-3 (Innogenetics), cuantificamos las proteínas Aβ1-42, T-tau, P-tau181p en LCR, y calculamos los cocientes T-tau/Aβ1-42 y P-tau181p/Aβ1-42. El estudio fue aprobado por el comité ético de investigación del Hospital General de Alicante. Resultados: En los 12 meses posteriores a la punción lumbar, 14 pacientes DCL (38%) evolucionaron a EA. Estos pacientes, presentaron menores niveles de Aβ1-42 (285,3 vs. 377,7 ng/ml, p<0,02), y un aumento en el valor del cociente P-tau181p/Aβ1-42 (0,25 vs. 0,16, p<0,02) que los pacientes que se mantuvieron estables. No hubo diferencias significativas en el resto de las variables estudiadas. Conclusiones: Nuestros pacientes DCL que presentaron niveles reducidos de la proteína Aβ1-42 y elevación del cociente P-tau181p/Aβ1-42 en LCR, evolucionaron rápidamente a EA. Estos resultados pueden ayudar a conseguir el objetivo de identificar de forma precoz a los pacientes DCL con peor pronóstico (AU)

Introduction: Some studies have shown that CSF amyloid-beta 1-42 (A_1-42), total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau181p) proteins are useful diagnostic markers for distinguishing between clinically stable mild cognitive impairment (MCI) patients and those who will develop Alzheimer's disease (AD). Our objective was to test the ability of this technique to discriminate in our cohort of MCI patients, according to the clinical outcome, one year after the lumbar puncture. Material and methods: A total of 36 MCI patients were included from the local hospital memory clinic. Using INNO-BIA Alzbio-3 reagents from Innogenetics, we measured CSF A_1-42, T-tau and P-tau181p proteins, and calculated the T-tau/A_1-42 y P-tau181p/A_1-42 ratios. Thisproject was approved by the local ethics committee. Results: One year after the lumbar puncture, 14 MCI patients (38%) developed AD. These patients had lower A_ 1-42 protein levels (285.3 vs 377 ng/ml, P < .02) and higher P-tau181p/A_1-42 ratio (0,25 vs 0,16, p < .02) than the clinically stable patients. Conclusions: Our MCI patients with lower A_1-42 protein levels and an increased P-tau181p /A_1-42 ratio progressed quickly to AD. These results may help to identify those MCI patients with a poorer prognosis (AU)

[Patients with mild cognitive impairment and a reduced CSF Aß1₋42 protein progress rapidly to Alzheimer's disease]. / Pacientes con deterioro cognitivo leve y reducción de la proteína Aß(1-42) en LCR evolucionan rápidamente a enfermedad de Alzheimer.

INTRODUCTION: Some studies have shown that CSF amyloid-beta 1-42 (Aß1₋42), total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau(181p)) proteins are useful diagnostic markers for distinguishing between clinically stable mild cognitive impairment (MCI) patients and those who will develop Alzheimers disease (AD). Our objective was to test the ability of this technique to discriminate in our cohort of MCI patients, according to the clinical outcome, one year after the lumbar puncture. MATERIAL AND METHODS: A total of 36 MCI patients were included from the local hospital memory clinic. Using INNO-BIA Alzbio-3 reagents from Innogenetics, we measured CSF Aß1₋42, T-tau and P-tau(181p) proteins, and calculated the T-tau/Aß1₋42 y P-tau(181p)/Aß1₋42 ratios. This project was approved by the local ethics committee. RESULTS: One year after the lumbar puncture, 14 MCI patients (38%) developed AD. These patients had lower Aß1₋42 protein levels (285.3 vs 377 ng/ml, P<.02) and higher P-tau(181p)/Aß1₋42 ratio (0,25 vs 0,16, p<.02) than the clinically stable patients. CONCLUSIONS: Our MCI patients with lower Aß1₋42 protein levels and an increased P-tau(181p) /Aß1₋42 ratio progressed quickly to AD. These results may help to identify those MCI patients with a poorer prognosis.

Dose-dependent effects of leucine supplementation on preservation of muscle mass in cancer cachectic mice.

Cancer cachexia, which is characterized by muscle wasting, is associated with increased morbidity and mortality. Because muscle protein synthesis may be increased and protein breakdown reduced by leucine supplementation, we used the C26 tumor-bearing cachectic mouse model to assess the effects of dietary supplementation with leucine on muscle weight and the markers of muscle protein breakdown (mRNA of atrogin and murf). Male CD2F1 mice were subcutaneously inoculated with tumor cells (tumor-bearing mice; TB) or were sham injected (control; C). They were fed standard diets or diets supplemented with leucine [1 gr (TB1Leu) or 8 gr (TB8Leu) supplemented leucine per kg feed]; TB and C received 8.7% Leu/g protein, TB1Leu received 9.6% Leu/g protein and TB8Leu received 14.6 Leu/g protein. After 21 days, the following were determined: body weights, plasma amino-acid concentrations, tumor size and muscle mass of the gastrocnemius (mG), tibialis anterior (mTA), extensor digitorum longus (mEDL) and soleus (mS) muscles. In tumor-bearing (TB) mice, carcass and skeletal muscle masses decreased, and levels of atrogin and murf mRNA in the mEDL increased. Muscle-mass loss was counteracted dose-dependently by leucine supplementation: relative to TB, the mass of the mG was +23% in TB8Leu, and +22% in mTA (p<0.05). However, leucine supplementation did not change atrogin and murf mRNA levels. Total plasma amino acid concentrations increased in TB, especially for taurine, lysine, arginine and alanine (p<0.05). Leucine supplementation attenuated the increase in total plasma amino-acid concentrations (p<0.05). Irrespective of changes in muscle protein breakdown markers, leucine supplementation reduced muscle wasting in tumor-bearing cachectic mice and attenuated changes in plasma amino acids.

Biomarkers of Alzheimer's disease in the cerebrospinal fluid of Spanish patients with mild cognitive impairment.

The study of biomarkers in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) is a technique used with increasing frequency in the early diagnosis of Alzheimers disease (AD). Our objectiv was to gain an own experience while evaluating the reliability, sensitivity, and reproducibility of this technique in Spanish patients. Thirty-seven patients with MCI and twenty-four control subjects were studied by means of AD biomarker analysis in CSF. xMAP Luminex and INNO-BIA Alzbio3 reagents of Innogenetics were used. The study variables assessed were levels of Aß(1-42), T-tau and P-tau(181p) proteins as well as the ratios of T-tau/Aß(1-42) and P-tau(181p)/Aß(1-42). Samples from nineteen patients were examined twice. Intra-class correlation coefficients for the three biomarkers used showed values higher than 0.95. We observed significant differences between the control group and the MCI groups. In the 6 months following lumbar puncture (LP), eleven (29%) patients with MCI developed AD. These patients showed significant lower levels in Aß(1-42) protein (276.35 ± 78 vs. 367.13 ± 123.49, P < 0.03) and higher ratios (T-tau/Aß(1-42) [0.38 ± 0.2 vs. 0.22 ± 0.14, P < 0.01] and P-tau(181p)/Aß(1-42) [0.27 ± 0.13 vs. 0.16 ± 0.1, P < 0.008]) to those in the same group who remained stable. We obtained similar results to those in the most recent reliable literature with our ROC curves, especially with our P-tau(181p) values and T-tau/Aß(1-42) ratio in order to differentiate between control and AD groups. Our experience showed that the analysis of CSF-AD biomarkers in patients with MCI is reliable, sensitive and reproducible. In our knowledge, this is the first experience in Spanish patients.

Do CSF biomarkers help clinicians predict the progression of mild cognitive impairment to dementia?

There is increasing interest in the value of CSF biomarkers to predict those individuals with mild cognitive impairment who will progress to dementia. However, lumbar puncture is not routine in these patients and biomarker assays are not universally available. To change clinical practice there must be very good evidence that biomarkers are helpful over and above clinical impression. Here we discuss the merits of CSF biomarkers compared with clinicians using simple bedside cognitive tests. Although every biomarker has a superior positive predictive value, most have inferior negative predictive values. When predicting the progression of mild cognitive impairment, the overall misclassification rate by clinicians using bedside cognitive tests is approximately 38% but this could be reduced to approximately 30% by using Abeta1-42 and to 24% with phosphorylated tau or total tau (or a combination of CSF biomarkers). Clinicians and patients together should decide whether this is sufficient to warrant the additional burden of a lumbar puncture, and the cost of the test, or whether further studies are needed before useful and clinically practical conclusions can be reached.

[Biomarkers in the cerebrospinal fluid of patients with mild cognitive impairment: a meta-analysis of their predictive capacity for the diagnosis of Alzheimer's disease]. / Biomarcadores en el liquido cefalorraquideo de pacientes con deterioro cognitivo leve: metaanalisis de su capacidad predictiva para el diagnostico de la enfermedad de Alzheimer.

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.

Biomarcadores en el líquido cefalorraquídeo de pacientes con deterioro cognitivo leve: metaanálisis de su capacidad predictiva para el diagnóstico de la enfermedad de Alzheimer / Biomarkers in the cerebrospinal fluid of patients with mild cognitive impairment: a meta-analysis of their predictive capacity for the diagnosis of Alzheimer’s disease

Introducción. Varios estudios han descrito alteraciones en los biomarcadores del líquido cefalorraquídeo (proteínas Abeta- 42, T-tau y P-tau), tanto en la enfermedad de Alzheimer (EA) como en el deterioro cognitivo leve (DCL). Objetivo. Realizar un metaanálisis sobre la rentabilidad diagnóstica de esta técnica para la predicción de los pacientes con DCL que van a progresar a EA. Materiales y métodos. Tras una búsqueda en PubMed y Embase de los artículos publicados entre 1999 y septiembre de 2008, se incluyeron sólo estudios prospectivos para la revisión sistemática. Se estudió la sensibilidad y especificidad para cada biomarcador por separado y también de forma conjunta.Resultados. De los 12 estudios incluidos, 6 cuantificaron la proteína Abeta-42, 11 la proteína T-tau y 7 la proteína P-tau. En tres estudios se pudieron obtener los datos de los tres biomarcadores de forma combinada. La sensibilidad de la cuantificación de las proteínas T-tau y P-tau es del 82%, con una odds ratio diagnóstica de 12,09 (intervalo de confianza al 95%, C 95% = 7,71-18,99; p = 0,1) y 16,29 (IC 95% = 9,69-27,4; p = 0,9), respectivamente. La alteración de alguno de los tres biomarcadores tiene una especificidad del 87%, con una odds ratio diagnóstica de 35,97 (IC 95% = 7,8-164,6; p = 0,04). Conclusiones. La alteración aislada de los niveles de T-tau o P-tau en el líquido cefalorraquídeo es muy sensible para diferenciar entre los pacientes con DCL que van a desarrollar EA de los que van a permanecer estables. La normalidad de los tres biomarcadores es muy fiable para descartar la evolución a EA en pacientes con DCL (AU)

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 (AU)

Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) "cachexia-anorexia in chronic wasting diseases" and "nutrition in geriatrics".

Chronic diseases as well as aging are frequently associated with deterioration of nutritional status, loss muscle mass and function (i.e. sarcopenia), impaired quality of life and increased risk for morbidity and mortality. Although simple and effective tools for the accurate screening, diagnosis and treatment of malnutrition have been developed during the recent years, its prevalence still remains disappointingly high and its impact on morbidity, mortality and quality of life clinically significant. Based on these premises, the Special Interest Group (SIG) on cachexia-anorexia in chronic wasting diseases was created within ESPEN with the aim of developing and spreading the knowledge on the basic and clinical aspects of cachexia and anorexia as well as of increasing the awareness of cachexia among health professionals and care givers. The definition, the assessment and the staging of cachexia, were identified as a priority by the SIG. This consensus paper reports the definition of cachexia, pre-cachexia and sarcopenia as well as the criteria for the differentiation between cachexia and other conditions associated with sarcopenia, which have been developed in cooperation with the ESPEN SIG on nutrition in geriatrics.

Versión española del test perfil de síntomas autonómicos / Spanish version of the autonomic symptom profile test

Resumen. Introducción. El perfil de síntomas autonómicos (PSA) es un cuestionario autorrellenable, que ha sido validado en lengua inglesa para valorar los síntomas autonómicos y diferenciar entre pacientes y sujetos sanos según dicha sintomatología. Nuestro grupo ha estudiado su aplicación en lengua castellana. Sujetos y métodos. Después de traducir al castellano la versión inglesa y retrotraducirla, se evaluó la fiabilidad y la validez de criterio de la versión española del test PSA en una muestra de 50 sujetos (27 controles y 23 enfermos). A todos los pacientes con síntomas de disfunción autonómica se les estudió mediante la batería de Ewing y Clarke. Resultados. La fiabilidad de la versión española del PSA fue alta, y se obtuvo un coeficiente de correlación intraclase de 0,93. Con una puntuación en el test de 47 o superior, se obtiene una sensibilidad del 73,9% y una especificidad del 100% para detectar disfunción autonómica. Además, la puntuación de la versión española del test PSA mostró diferencias estadísticamente significativas entre el grupo de pacientes y el grupo control. Conclusiones. La versión española del PSA es fiable y permite distinguir entre pacientes con disfunción autonómica y sujetos control. En nuestro conocimiento, se trata del primer test que valora la sintomatología del sistema nervioso autónomo de forma global y en castellano (AU)

Summary. Introduction. The Autonomic Symptom Profile (ASP) is a self-administered questionnaire that has been validated in English to assess autonomic symptoms and to differentiate between patients and healthy subjects according to said symptoms. Our group has studied its application in Spanish. Subjects and methods. After translating the English version into Spanish and then back-translating it, the reliability and validity of criteria in the Spanish version of the ASP test were evaluated in a sample of 50 subjects (27 controls and 23 patients). All the patients with symptoms of autonomic dysfunction were studied by means of the Ewing and Clarke battery. Results. The reliability of the Spanish version of the ASP was high and an interclass correlation coefficient of 0.93 was obtained. A score of 47 or over in the test yields a sensitivity of 73.9% and a specificity of 100% for the detection of autonomic dysfunction. Furthermore, the score in the Spanish version of the ASP test showed statistically significant differences between the group of patients and the control group. Conclusions. The Spanish version of the ASP is reliable and makes it possible to distinguish between patients with autonomic dysfunction and control subjects. As far as we are aware, this is the first test to evaluate the symptoms of the autonomic nervous system in a global manner and in Spanish (AU)

[Spanish version of the Autonomic Symptom Profile test]. / Versión española del test perfil de síntomas autonómicos.

INTRODUCTION: The Autonomic Symptom Profile (ASP) is a self-administered questionnaire that has been validated in English to assess autonomic symptoms and to differentiate between patients and healthy subjects according to said symptoms. Our group has studied its application in Spanish. SUBJECTS AND METHODS: After translating the English version into Spanish and then back-translating it, the reliability and validity of criteria in the Spanish version of the ASP test were evaluated in a sample of 50 subjects (27 controls and 23 patients). All the patients with symptoms of autonomic dysfunction were studied by means of the Ewing and Clarke battery. RESULTS: The reliability of the Spanish version of the ASP was high and an interclass correlation coefficient of 0.93 was obtained. A score of 47 or over in the test yields a sensitivity of 73.9% and a specificity of 100% for the detection of autonomic dysfunction. Furthermore, the score in the Spanish version of the ASP test showed statistically significant differences between the group of patients and the control group. CONCLUSIONS: The Spanish version of the ASP is reliable and makes it possible to distinguish between patients with autonomic dysfunction and control subjects. As far as we are aware, this is the first test to evaluate the symptoms of the autonomic nervous system in a global manner and in Spanish.

[Two years' experience in a specific autonomic nervous system service]. / Experiencia de dos años en una consulta específica de sistema nervioso autónomo.

INTRODUCTION: Despite the high incidence and prevalence of pathologies affecting the autonomic nervous system (ANS), this part of neurology has received very little specific attention in clinical care in our country. AIM: To present the experience we have gained over a two-year period in an ANS-specific service. PATIENTS AND METHODS: Our patients were referred to the ANS service by other colleagues, most of whom were neurologists, between April 2006 and April 2008, after proposing a set of eligibility and exclusion criteria. Clinical history, examination and general analysis were performed for all patients. The following tests were also carried out on an individualised basis: Ewing-Clarke test, the Spanish version of the autonomic symptom profile test, tilt table test, holter heart monitor, urodynamic study and reflex sympathetic test, among other complementary studies. RESULTS: Thirty-four first visits and 62 successive visits were registered. The most frequent diagnoses were neurologically mediated syncopes and diabetic autonomic neuropathies, but other less prevalent conditions were also diagnosed. The most cost-effective complementary tests were the Ewing-Clarke test and the autonomic symptom profile test. Apart from benzodiazepines, the most commonly prescribed pharmacological treatments were paroxetine and pyridostigmine. CONCLUSIONS: As expected, neurologically mediated syncopes and diabetic neuropathies with an autonomic component are the most frequent pathologies in an ANS service. Nevertheless, their diagnosis and individualised treatment, together with that of other less prevalent autonomic pathologies, may require specific attention. To our knowledge, this is the first service of its kind in our country.

Experiencia de dos años en una consulta específica de sistema nervioso autónomo / Two years'experience in a specific autonomic nervous system service

Introducción. A pesar de la alta incidencia y prevalencia de la patología del sistema nervioso autónomo (SNA), esta parte de la neurología apenas ha merecido una atención específica en la asistencia clínica de nuestro país. Objetivo. Presentar nuestra experiencia de dos años en una consulta específica de SNA. Pacientes y métodos. Pacientes enviados a la consulta de SNA por otros compañeros, en su mayoría neurólogos, entre abril de 2006 y abril de 2008, tras proponer unos criterios de inclusión y exclusión. A todos los pacientes se les realizó anamnesis, exploración y analítica general. De forma individualizada, se realizaron test de Ewing-Clarke, versión española del test perfil de síntomas autonómicos, test de la mesa basculante, holter cardíaco, estudio urodinámico y test simpático reflejo, entre otros estudios complementarios. Resultados. Se realizaron 34 primeras consultas y 62 sucesivas. Los diagnósticos más frecuentes fueron los síncopes neurológicamente mediados y las neuropatías diabéticas autonómicas, pero se han diagnosticado otras entidades menos prevalentes. Las pruebas complementarias más rentables fueron el test de Ewing-Clarke y el test perfil de síntomas autonómicos. Los tratamientos farmacológicos más prescritos han sido, aparte de las benzodiacepinas, la paroxetina y la piridostigmina. Conclusiones. Como cabía esperar, los síncopes neurológicamente mediados y las neuropatías diabéticas con componente autonómico son las patologías más frecuentes en una consulta de SNA. Sin embargo, su diagnóstico y tratamiento individualizado, así como el de otras patologías autonómicas menos prevalentes, pueden requerir una atención específica. En nuestro conocimiento, se trata de la primera consulta de estas características en nuestro país (AU)

Introduction. Despite the high incidence and prevalence of pathologies affecting the autonomic nervous system (ANS), this part of neurology has received very little specific attention in clinical care in our country. Aim. To present the experience we have gained over a two-year period in an ANS-specific service. Patients and methods. Our patients were referred to the ANS service by other colleagues, most of whom were neurologists, between April 2006 and April 2008, after proposing a set of eligibility and exclusion criteria. Clinical history, examination and general analysis were performed for all patients. The following tests were also carried out on an individualised basis: Ewing-Clarke test, the Spanish version of the autonomic symptom profile test, tilt table test, holter heart monitor, urodynamic study and reflex sympathetic test, among other complementary studies. Results. Thirty-four first visits and 62 successive visits were registered. The most frequent diagnoses were neurologically mediated syncopes and diabetic autonomic neuropathies, but other less prevalent conditions were also diagnosed. The most cost-effective complementary tests were the Ewing-Clarke test and the autonomic symptom profile test. Apart from benzodiazepines, the most commonly prescribed pharmacological treatments were paroxetine and pyridostigmine. Conclusions. As expected, neurologically mediated syncopes and diabetic neuropathies with an autonomic component are the most frequent pathologies in an ANS service. Nevertheless, their diagnosis and individualised treatment, together with that of other less prevalent autonomic pathologies, may require specific attention. To our knowledge, this is the first service of its kind in our country (AU)