Dataset Information

Added Diagnostic Value of Cerebrospinal Fluid Biomarkers for Differential Dementia Diagnosis in an Autopsy-Confirmed Cohort.

ABSTRACT:

Background

Differential dementia diagnosis remains a challenge due to overlap of clinical profiles, which often results in diagnostic doubt.

Objective

Determine the added diagnostic value of cerebrospinal fluid (CSF) biomarkers for differential dementia diagnosis as compared to autopsy-confirmed diagnosis.

Methods

Seventy-one dementia patients with autopsy-confirmed diagnoses were included in this study. All neuropathological diagnoses were established according to standard neuropathological criteria and consisted of Alzheimer's disease (AD) or other dementias (NONAD). CSF levels of A?1 - 42, T-tau, and P-tau181 were determined and interpreted based on the IWG-2 and NIA-AA criteria, separately. A panel of three neurologists experienced with dementia made clinical consensus dementia diagnoses. Clinical and CSF biomarker diagnoses were compared to the autopsy-confirmed diagnoses.

Results

Forty-two patients (59%) had autopsy-confirmed AD, whereas 29 patients (41%) had autopsy-confirmed NONAD. Of the 24 patients with an ambiguous clinical dementia diagnosis, a correct diagnosis would have been established in 67% of the cases applying CSF biomarkers in the context of the IWG-2 or the NIA-AA criteria respectively.

Conclusion

AD CSF biomarkers have an added diagnostic value in differential dementia diagnosis and can help establishing a correct dementia diagnosis in case of ambiguous clinical dementia diagnoses.

SUBMITTER: Niemantsverdriet E

PROVIDER: S-EPMC5900550 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Added Diagnostic Value of Cerebrospinal Fluid Biomarkers for Differential Dementia Diagnosis in an Autopsy-Confirmed Cohort.

Niemantsverdriet Ellis E Feyen Bart F E BFE Le Bastard Nathalie N Martin Jean-Jacques JJ Goeman Johan J De Deyn Peter Paul PP Bjerke Maria M Engelborghs Sebastiaan S

Journal of Alzheimer's disease : JAD 20180101 1

<h4>Background</h4>Differential dementia diagnosis remains a challenge due to overlap of clinical profiles, which often results in diagnostic doubt.<h4>Objective</h4>Determine the added diagnostic value of cerebrospinal fluid (CSF) biomarkers for differential dementia diagnosis as compared to autopsy-confirmed diagnosis.<h4>Methods</h4>Seventy-one dementia patients with autopsy-confirmed diagnoses were included in this study. All neuropathological diagnoses were established according to standard ...[more]

PMID: 29614653

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Project description:ObjectiveThe prognostic value of cerebrospinal fluid neurofilament light chain, total tau, phosphorylated tau181, and amyloid beta1-42 was examined in frontotemporal dementia subtypes.MethodsWe compared baseline biomarkers between 49 controls, 40 patients with behavioral variant frontotemporal dementia, 24 with semantic variant primary progressive aphasia, and 26 with nonfluent variant primary progressive aphasia. Linear mixed effect models were used to assess the value of baseline biomarkers in predicting clinical and radiographic change in patient cohorts over multiple yearly follow up visits.ResultsNeurofilament light chain concentrations were lowest in controls. Elevated baseline neurofilament light chain predicted faster worsening in clinical severity, frontotemporal volume and frontotemporal fractional anisotropy in patients with behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. High total tau similarly predicted faster progression in nonfluent variant primary progressive aphasia. In behavioral variant frontotemporal dementia, higher phosphorylated tau181 predicted faster clinical progression whereas lower amyloid beta1-42 predicted faster volumetric and fractional anisotropy reduction. Neurofilament light chain and phosphorylated tau181 were of greater predictive value in patients with tau pathology as compared to TDP-43 pathology. Baseline neurofilament light chain correlated with baseline clinical severity and frontotemporal volume in behavioral variant frontotemporal dementia. Baseline total tau correlated with baseline clinical severity in semantic variant primary progressive aphasia.InterpretationHigh cerebrospinal fluid neurofilament light chain predicts more aggressive disease in behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. Total tau, phosphorylated tau181, and amyloid beta1-42 also predict some measures of disease aggressiveness in frontotemporal dementia.

Project description:The goal of this study is to investigate the value of tau phosphorylated at threonine 181 (P-tau181P) in the Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker panel for differential dementia diagnosis in autopsy confirmed AD and non-AD patients. The study population consisted of 140 autopsy confirmed AD and 77 autopsy confirmed non-AD dementia patients. CSF concentrations of amyloid-? peptide of 42 amino acids (A?1-42), total tau protein (T-tau), and P-tau181P were determined with single analyte ELISA-kits (INNOTEST(®), Fujirebio, Ghent, Belgium). Diagnostic accuracy was assessed through receiver operating characteristic (ROC) curve analyses to obtain area under the curve (AUC) values and to define optimal cutoff values to discriminate AD from pooled and individual non-AD groups. ROC curve analyses were only performed on biomarkers and ratios that differed significantly between the groups. Pairwise comparison of AUC values was performed by means of DeLong tests. The A?1-42/P-tau181P ratio (AUC?=?0.770) performed significantly better than A?1-42 (AUC?=?0.677, P?=?0.004), T-tau (AUC?=?0.592, P?<?0.001), and A?1-42/T-tau (AUC?=?0.678, P?=?0.001), while P-tau181P (AUC?=?0.720) performed significantly better than T-tau (AUC?=?0.592, P?<?0.001) to discriminate between AD and the pooled non-AD group. When comparing AD and the individual non-AD diagnoses, A?1-42/P-tau181P (AUC?=?0.894) discriminated AD from frontotemporal dementia significantly better than A?1-42 (AUC?=?0.776, P?=?0.020) and T-tau (AUC?=?0.746, P?=?0.004), while P-tau181P/T-tau (AUC?=?0.958) significantly improved the differentiation between AD and Creutzfeldt-Jakob disease as compared to A?1-42 (AUC?=?0.688, P?=?0.004), T-tau (AUC?=?0.874, P?=?0.040), and A?1-42/P-tau181P (AUC?=?0.760, P?=?0.003). In conclusion, this study demonstrates P-tau181P is an essential component of the AD CSF biomarker panel, and combined assessment of A?1-42, T-tau, and P-tau181P renders, to present date, the highest diagnostic power to discriminate between AD and non-AD dementias.

Dataset Information

Added Diagnostic Value of Cerebrospinal Fluid Biomarkers for Differential Dementia Diagnosis in an Autopsy-Confirmed Cohort.

Background

Objective

Methods

Results

Conclusion

Publications

Added Diagnostic Value of Cerebrospinal Fluid Biomarkers for Differential Dementia Diagnosis in an Autopsy-Confirmed Cohort.

Similar Datasets

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