Diagnostic impact of CSF biomarkers in a local hospital memory clinic.

Alzheimer Center, Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
Dementia and Geriatric Cognitive Disorders (Impact Factor: 2.81). 01/2010; 29(6):491-7. DOI: 10.1159/000313534
Source: PubMed

ABSTRACT CSF biomarkers amyloid-beta 1-42 (Abeta42), total tau (tau) and tau phosphorylated at threonine 181 (ptau-181) are useful diagnostic markers for Alzheimer's disease (AD). We examined the impact of these biomarkers in the diagnostic process in a non-academic memory clinic.
One hundred and nine patients with available CSF were included from the local hospital memory clinic. Initially, patients were clinically diagnosed, and the clinician indicated their confidence in the diagnosis. Next the CSF results were presented, and the clinician re-evaluated his initial diagnosis. The main outcomes were changes in initial diagnosis and diagnostic confidence.
Forty-seven patients were initially diagnosed with AD, 26 were diagnosed with another type of dementia, 18 were diagnosed with mild cognitive impairment, and 18 received a non-dementia diagnosis. All biomarkers distinguished between AD and non-dementia (p < 0.01); tau and ptau-181 also distinguished AD from other types of dementia (p < 0.001). After CSF biomarker levels were revealed, 11 diagnoses changed. In 31% of the diagnoses, the clinician gained confidence, while in 10% confidence decreased.
We found that knowledge of CSF biomarker profiles changed the diagnosis in 10% of the cases, and confidence in the diagnosis increased for one third of the patients.

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    • "Les biomarqueurs seraient, dans ce cas-là, des critères de substitution [13] [14]. En effet, il a été montré que ces biomarqueurs contribuaient à une réorientation diagnostique dans environ 10 % des cas [14]. Lorsqu'ils sont utilisés séparément (A␤1-42, Tau et P-Tau), chacun des trois biomarqueurs a une Se et une Sp de plus de 80 % pour détecter la maladie d'Alzheimer. "
    NPG Neurologie - Psychiatrie - Gériatrie 03/2015;
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    • "Despite this growing concern about CSF biomarker variability in experimental studies, little is known about the use of CSF biomarkers in routine clinical practice [27], and scarce data regarding optimum cutoffs are available. Therefore , we investigated the diagnostic accuracy and optimum threshold values of CSF biomarkers and intercenter variability in a large cohort of subjects from three French memory centers in which the use of lumbar punctures is frequent in the clinical setting to explore cognitive disorders. "
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    ABSTRACT: BACKGROUND: The assessment of total tau, phosphorylated tau (pTau-181) and amyloid beta (Aβ 1-42) concentrations in the cerebrospinal fluid (CSF) of subjects has been validated for the diagnosis of Alzheimer's disease (AD). Although these measurements have shown some variability, little is known about their intersite variability in clinical settings. METHODS: A total of 880 subjects (AD, n = 515; non-AD, n = 365) from three French memory centers were included. Receiver-operating characteristic analyses were performed to computerized area under curves (AUCs) and optimal thresholds for each biomarker in the three centers. A test-retest study was performed in a group of 32 CSF samples by repeated blind analysis of the three biomarkers using the same immunoassay batches in the three centers. RESULTS: In the three centers, tau (AUC, 0.82-0.88) and pTau-181 (AUC, 0.83-0.89) outperformed Aβ 1-42 (AUC, 0.70 -0.73) to discriminate subjects with AD from those without AD. An intersite variation of mean levels and cutoffs was observed for the three biomarkers. This variation was higher for Aβ 1-42 (range of cutoff, 368-582 pg/mL) than for tau (range of cutoff, 289-353 pg/mL). In a test-retest study, the mean interlaboratory coefficients of variation were 12.2% for Aβ 1-42, 11.3% for tau, and 11.5% for pTau-181. CONCLUSION: Intercenter variability of CSF biomarkers has been confirmed in a multisite cohort of subjects and can be improved in clinical settings. Efforts on harmonization of procedures should be encouraged to optimize the accuracy of CSF biomarkers in AD.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 11/2012; 9(4). DOI:10.1016/j.jalz.2012.06.006 · 17.47 Impact Factor
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    • "Amyloid beta (Ab) is a major constituent of senile plaques in Alzheimer disease (AD). Its measurement in cerebrospinal fluid (CSF), together with tau proteins, may increase confidence in the diagnosis for one third of all AD patients (Kester et al. 2010). The majority of AD cases occur as late onset disorder after 65 years where underlying disease processes are widely unknown. "
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    ABSTRACT: An association between plasma Amyloid beta peptides (Aβ) with blood lipids was reported in cross-sectional studies. The present study examined the 5-year prospective association of atherosclerotic risk factors with plasma Aβ42 in 440 elderly persons without both Alzheimer's disease (AD) or mild cognitive impairment (MCI) at baseline. Persons in the highest tertile of total cholesterol (TC) or LDL-C at baseline showed low plasma Aβ42 at 5 years. Regression analysis confirmed TC and LDL-C as negative predictors of Aβ42 (p = 0.001). An increase over 5 years of HDL-C was a negative predictor and the presence of an APOE ε4 allele was a positive predictor for decrease of Aβ42 in converters to MCI. In converters to AD, increase of both TC and of HbA1c were positive predictors of Aβ42 levels at 5 years. Analysis of covariance showed a positive association between Δ-TC, Δ-LDL-C, Δ-HbA1c, and levels of Aβ42 at 5 years (p = 0.006; 0.013 and 0.027 resp.) in converters to AD independently on lipid-lowering treatment. The association of vascular risk factors TC, LDL-C, and HbA1c with higher Aβ42 levels might, after confirmation in other cohorts, influence the development of lifestyle interventions concerning plasma Aβ42 and AD.
    Journal of Neural Transmission 02/2011; 118(5):663-72. DOI:10.1007/s00702-011-0599-4 · 2.87 Impact Factor
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