Event-related Potentials Improve the Efficiency of Cerebrospinal Fluid Biomarkers for Differential Diagnosis of Alzheimer’s Disease

2018 ◽  
Vol 15 (13) ◽  
pp. 1244-1260 ◽  
Author(s):  
Mirjana Babić Leko ◽  
Magdalena Krbot Skorić ◽  
Nataša Klepac ◽  
Fran Borovečki ◽  
Lea Langer Horvat ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cerebrospinal Fluid ◽  
Differential Diagnosis ◽  
Tau Protein ◽  
Strong Correlation ◽  
Event Related Potentials ◽  
P300 Latency ◽  
Protein Biomarkers ◽  
Related Potentials ◽  
T Tau

Introduction: The pathological process of Alzheimer's disease (AD) in the brain likely begins 20-30 years earlier than the emergence of its first clinical symptoms and symptoms of AD often overlap with the symptoms of other primary causes of dementia. Therefore, it is crucially important to improve early and differential diagnosis of the disease. Event-related potentials (ERP) measured non-invasively by electroencephalography have shown diagnostic potential in AD. Aims: The aim of this study was to compare the efficiency of P300 and N200 potentials and reaction time (RT) with commonly used protein biomarkers measured in the cerebrospinal fluid (CSF), including amyloid β peptide (β1-42), total tau (t-tau), tau protein phosphorylated at threonine 181 (p-tau181), tau protein phosphorylated at serine 199 (p-tau199), tau protein phosphorylated at threonine 231 (p-tau231), and visinin-like protein 1 (VILIP-1) in differential diagnosis of AD in mild cognitive impairment (MCI) and AD patients. Subjects: The study involved 49 AD patients, 28 patients with MCI, 4 healthy control subjects and 16 patients with other primary causes of dementia. Results: ERP (P300RT, N200RT, P300 counting and N200 counting) showed a moderate to strong correlation with protein CSF biomarkers. We confirmed previous observations of moderate to strong correlation between ERP and neuropsychological testing and showed that P300 latency and RT are shortened in AD patients on therapy with acetylcholinesterase inhibitors. Using ERP and RT, a predictive model for determination of AD likelihood in MCI patients was developed, detecting 56.3% of MCI patients with high risk for development of AD in our cohort. MCI patients with pathological levels of Aβ1-42 had prolonged P300 latency, indicating that a combination of ERP and CSF protein biomarkers could improve the differential diagnosis of AD in MCI patients. Additionally, the results suggested the potential of P300 latency in differentiating AD and FTD patients. Conclusion: Our data provide possible solutions for improvement of differential diagnosis of AD, and reveal that the diagnostic efficiency of CSF protein biomarkers t-tau, p-tau181, p-tau199, p-tau231 and VILIP-1 could be improved by adding ERP in clinical practice.

A new tetra-plex fluorimetric assay for the quantification of cerebrospinal fluid β-amyloid42, total-tau, phospho-tau and α-synuclein in the differential diagnosis of neurodegenerative dementia.

2020 ◽  
Author(s):  
Daniela Diaz Lucena ◽  
Geòrgia Escaramis ◽  
Anna Villar-Piqué ◽  
Peter Hermann ◽  
Matthias Schmitz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Differential Diagnosis ◽  
Discriminant Analysis ◽  
Least Squares ◽  
Total Tau ◽  
Neurodegenerative Dementia ◽  
Jakob Disease ◽  
T Tau

Abstract Background Differential diagnosis of neurodegenerative dementia is currently supported by biomarkers including cerebrospinal fluid (CSF) tests. Among them, CSF total-tau (t-tau), phosphorylated tau (p-tau) and β-amyloid42 (Aβ42) are considered core biomarkers of neurodegeneration. In the present work, we hypothesize that simultaneous assessment of these biomarkers together with CSF α-synuclein (α-syn) will significantly improve the differential diagnostic of Alzheimer’s disease and other dementias. To that aim, we characterized the analytical and clinical performance of a new tetra-plex immunoassay that simultaneously quantifies CSF Aβ42, t-tau, p-tau and α-syn in the differential diagnosis of neurodegenerative dementia. Methods Biomarkers’ concentrations were measured in neurological controls (n=38), Alzheimer’s disease (n=35), Creutzfeldt-Jakob disease (n=37), vascular dementia (n=28), dementia with Lewy bodies/Parkinson’s disease dementia (n=27) and frontotemporal dementia (n=34) using the new tetra-plex assay and established single-plex assays. Biomarker’s performance was evaluated and diagnostic accuracy in the discrimination of diagnostic groups was determined using partial least squares discriminant analysis. Results The tetra-plex assay presented accuracies similar to individual single-plex assays with acceptable analytical performance. Significant correlations were observed between tetra-plex and single-plex assays. Using partial least squares discriminant analysis, Alzheimer’s disease and Creutzfeldt-Jakob disease were well-differentiated, reaching high accuracies in the discrimination from the rest of diagnostic groups. Conclusions The new tetra-plex assay coupled with multivariate analytical approaches becomes a valuable asset for the differential diagnosis of neurodegenerative dementia and related applications.

scholarly journals Cerebrospinal Fluid Biomarkers for the Diagnosis of Prodromal Alzheimer’s Disease in Amnestic Mild Cognitive Impairment

2019 ◽  
Vol 9 (1) ◽  
pp. 100-113 ◽  
Author(s):  
Jung Eun Park ◽  
Kyu Yeong Choi ◽  
Byeong C. Kim ◽  
Seong-Min Choi ◽  
Min-Kyung Song ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Tau Protein ◽  
Amnestic Mild Cognitive Impairment ◽  
Csf Biomarkers ◽  
Cutoff Values ◽  
Prodromal Ad ◽  
T Tau

Background/Aims: Disease-modifying therapy for Alzheimer’s disease (AD) has led to a need for biomarkers to identify prodromal AD and very early stage of AD dementia. We aimed to identify the cutoff values of cerebrospinal fluid (CSF) biomarkers for detecting prodromal AD. Methods: We assessed 56 patients with amnestic mild cognitive impairment (aMCI) who underwent lumbar puncture. Additionally, 87 healthy elderly individuals and 34 patients with AD dementia served as controls. Positron emission tomography was performed using florbetaben as a probe. We analyzed the concentration of Aβ1–42, total tau protein (t-Tau), and tau protein phosphorylated at threonine 181 (p-Tau181) in CSF with INNOTEST enzyme-linked immunosorbent assay. Results: For the detection of prodromal AD in patients with aMCI, the cutoff values of CSF Aβ1–42, t-Tau, and p-Tau181 were 749.5 pg/mL, 225.6 pg/mL, and 43.5 pg/mL, respectively. To discriminate prodromal AD in patients with aMCI, the t-Tau/Aβ1–42 and ­p-Tau181/Aβ1–42 ratios defined cutoff values at 0.298 and 0.059, respectively. Conclusions: CSF biomarkers are very useful tools for the differential diagnosis of prodromal AD in aMCI patients. The concentration of CSF biomarkers is well correlated with the stages of the AD spectrum.

On the value of P300 Event-Related Potentials in the Differential Diagnosis of Dementia

1984 ◽  
Vol 145 (6) ◽  
pp. 652-656 ◽  
Author(s):  
J. P. J. Slaets ◽  
C. Fortgens
Keyword(s):  
Differential Diagnosis ◽  
Elderly Patients ◽  
Auditory Evoked Potentials ◽  
Event Related Potentials ◽  
P300 Latency ◽  
Age Related ◽  
Significant Difference ◽  
Diagnosis Of Dementia ◽  
Related Potentials ◽  
Differential Diagnosis Of Dementia

SummaryThe possible value of event-related potentials (ERPs) in the differential diagnosis of dementia was investigated in a group of 42 demented elderly patients, 29 non-demented elderly patients, and 10 healthy young controls. The auditory evoked potentials were elicited by using target and non-target auditory stimuli. There was no significant difference in N100 and P200 latency between these groups. Our results indicate an age-related increase of P300 latency of 0.3 msec/year in the non-demented subjects. There was no significant difference in P300 latency between demented and non-demented patients, and the latencies vary widely within the groups of elderly patients.

scholarly journals Cerebrospinal fluid amyloid beta and tau protein: Biomarkers for Alzheimer's disease

2008 ◽  
Vol 65 (12) ◽  
pp. 901-905
Author(s):  
Gorana Mandic ◽  
Ivanka Markovic ◽  
Marija Ostojic ◽  
Tanja Stojkovic ◽  
Sonja Misirlic-Dencic ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Tau Protein ◽  
Symptomatic Treatment ◽  
Amyloid Peptide ◽  
Control Group ◽  
Csf Biomarkers ◽  
Diagnostic Potential ◽  
T Tau

Background/Aim. Introduction of acetylcholine esterase inhibitors as a symptomatic treatment of Alzheimer's disease (AD) has additionally highlighted the importance of diagnostic markers in cerebrospinal fluid (CSF) for early AD diagnosis: low level of 42 amino acid form of amyloid-? peptide (A?42), and levels of tau protein (T-tau) and phosphorylated tau protein (P-tau). The aim of this study was to diagnostic potential of CSF biomarkers T-tau, P-tau and A?42 as biochemical markers for AD. Methods. Lumbar puncture was performed in 63 patients with AD and 26 control subjects who passed orthopedic surgery. The Innotest, ELISA sandwich test (Innogenetics - Belgium) was used for measuring the levels of T-tau, P-tau and A?42. Results. The patients and the control group did not differ in age, education and sex. Mean levels of CSF T-tau and P-tau were significantly higher in the patients with AD (p < 0.001) compared to the control group, in contrast to significantely lower CSF A?42 in AD group (p < 0.001). A significant progressive decrease of A?42, as well as significant progressive increase of T-tau and P-tau was found among AD subgroups (according to MMSE staging) and controls. Conclusion. The obtained results suggest that these biomarkers may be supportive in the diagnosis of AD, especially in the early course of the disease and could be used in the routine clinical practice considering the approaching target therapeutics.

scholarly journals Cortical function in Alzheimer’s disease and frontotemporal dementia

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Pan Wang ◽  
Huihong Zhang ◽  
Lu Han ◽  
Yuying Zhou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Motor Cortex ◽  
Frontotemporal Dementia ◽  
Silent Period ◽  
Event Related Potentials ◽  
P300 Latency ◽  
Cortical Function ◽  
Motor Cortex Excitability ◽  
Related Potentials

AbstractObjectivesAlzheimer’s disease (AD) and the behavioral variant of frontotemporal dementia (bvFTD) are the most common causes of dementia; however, their overlapping clinical syndromes and involved brain regions make a differential diagnosis difficult. We aimed to identify the differences in the cognition and motor cortex excitability between AD and bvFTD patients.MethodsTwenty-seven AD patients and 30 bvFTD patients were included in the study. Each participant received a neurological evaluation. Cognitive event-related potentials (P300) were recorded during an auditory oddball task. Next, the excitability of the motor cortex, including the resting, facilitated motor threshold (RMT and FMT) and cortical silent period (CSP), were assessed during transcranial magnetic stimulation (TMS).ResultsThe bvFTD patients exhibited significantly longer P300 latencies compared with AD patients. There was a significant negative correlation between cognition and P300 latency in the bvFTD group. The AD patients showed significantly reduced RMT and FMT values compared to the bvFTD group; however, no significant correlation was found between AD severity and the excitability of the motor cortex.ConclusionsCognition and motor cortical functions are different between AD and bvFTD patients. Noninvasive electrophysiological examinations have the potential to identify unique pathophysiological features that can be used to differentially diagnose AD and bvFTD patients.

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