Diagnostic impact of CSF biomarkers in a local hospital memory clinic.
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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ABSTRACT: Background Cerebrospinal fluid (CSF) proteins have become accepted biomarkers of Alzheimer's disease (AD) in research settings. The extent of their use, perceived utility, and influence on decision making in clinical settings, however, are less well studied. Methods Clinicians who evaluate older adults (N = 193) were randomized to view normal, borderline, AD-consistent, or no CSF information in two vignettes portraying patients with borderline and mild AD symptoms. Clinicians also reported on the use and perceived utility of CSF biomarkers. Results Although clinicians reported infrequent use and low perceived utility of CSF biomarkers, viewing AD-consistent CSF values made clinicians more likely to make an AD-related diagnosis, increased diagnostic confidence, and led clinicians to initiate treatment more often than clinicians who had no CSF information. Conclusions CSF biomarkers influence decision making depending on the extent to which biomarkers reflect AD pathology, consistency between clinical–pathologic information, and the ambiguity of protein values.Alzheimer's and Dementia 07/2014; 11(5). DOI:10.1016/j.jalz.2014.04.517 · 17.47 Impact Factor
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ABSTRACT: Alzheimer's disease is the most common form of dementia, characterized by the progressive accumulation of plaques with amyloid-beta peptide of 42 amino acids as one of the primary constituents. A disposable electrochemical immunosensor for the detection of amyloid-beta 1-42 is developed. Screen-Printed Carbon Electrodes nanostructured with gold nanoparticles generated “in situ” are used as the transducer surface. The immunosensing strategy consists in a competitive immunoassay: biotin-amyloid-beta 1-42 immobilized on the electrode surface and the analyte (amyloid-beta 1-42) compete for the anti-amyloid-beta 1-42 antibody. The electrochemical detection is carried out using an alkaline phosphatase labeled anti-rabbit IgG antibody. The analytical signal is based on the anodic stripping of enzymatically generated silver by cyclic voltammetry. The immunosensor achieved shows a low limit of detection (0.1 ng/mL) and a wide linear range (0.5-500 ng/mL).Sensors and Actuators B Chemical 10/2014; 201:567-571. DOI:10.1016/j.snb.2014.05.044 · 3.84 Impact Factor
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ABSTRACT: Objectives. To determine how beta-amyloid 1-42 (Aβ 1-42), total tau (tTau), and phosphorylated tau (pTau) levels in CSF behave in a cohort of Thai patients from the Memory Clinic in Bangkok, Thailand. Methods. During 2009-2011, twenty eight subjects from the memory clinic at Siriraj Hospital had CSF analysis for AD biomarkers. Aβ 1-42, tTau, and pTau (at amino acid 181) were measured in CSF by ELISA technique. Results. Mean of Thai mental state examination (TMSE) of 28 Thai cohort was 16.48 (6.63). Fourteen had AD, ten had non-AD dementia, and four non-cases were those with subjective memory complaint (SMC) without dementia. Mean CSF Aβ 1-42, tTau, ptau (181), and pTau/Aβ 1-42 in the AD group were 241.36 (60.14) pg/mL, 222.79 (212.24) pg/mL, 40.79 (27.84) pg/mL, and 0.18 (0.12) accordingly. Mean CSF Aβ 1-42, tTau, pTau (181), and pTau/Aβ 1-42 in the non-AD dementia group were 430.40 (125.18) pg/mL, 349.30 (692.16) pg/mL, 36.80 (14.90) pg/mL, and 0.09 (0.04) accordingly. Mean CSF Aβ 1-42, tTau, pTau (181), and pTau/Aβ 1-42 in the non-cases with SMC without dementia were 499.75 (93.44) pg/mL, 137.25 (62.74) pg/mL, 31.75 (17.48) pg/mL, and 0.06 (0.02). There is significant difference (P < 0.05) among the 3 groups in CSF Aβ 1-42 and pTau/Aβ 1-42. We propose mean + 1.5 SD of CSF Aβ 1-42 in AD group (331.57 pg/mL) to be the cut-off point in Thai subjects. Conclusion. There are significant different in CSF Aβ 1-42 and CSF p-tau/Aβ 1-42 among those with AD, non-AD dementia and non cases with SMC without dementia in Thai cohort. Cut-off point of CSF Aβ 1-42 of 331.57 pg/mL is suggested in Thai study.07/2012; 2012:212063. DOI:10.1155/2012/212063