Measurement of CSF α-synuclein improves early differential diagnosis of mild cognitive impairment due to Alzheimer's disease.

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/.

Measuring executive dysfunction in Parkinson's disease: Reliability and validity of the Spanish version of Frontal Assessment Battery (FAB-E).

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.

Comparison of two analytical platforms for CSF biomarkers of Alzheimer's disease.

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.

[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.