Matching Clinical Diagnosis and Amyloid Biomarkers in Alzheimer's Disease and Frontotemporal Dementia.

ABSTRACT

BACKGROUND: The aims of this study were to compare the diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of different cerebrospinal fluid (CSF) amyloid biomarkers and amyloid-Positron Emission Tomography (PET) in patients with a clinical diagnosis of Alzheimer's disease (AD) and Frontotemporal Dementia (FTD); to compare concordance between biomarkers; and to provide an indication of their use and interpretation. METHODS: We included 148 patients (95 AD and 53 FTD), who underwent clinical evaluation, neuropsychological assessment, and at least one amyloid biomarker (CSF analysis or amyloid-PET). Thirty-six patients underwent both analyses. One-hundred-thirteen patients underwent Apolipoprotein E (ApoE) genotyping. RESULTS: Amyloid-PET presented higher diagnostic accuracy, sensitivity, and NPV than CSF Aß1-42 but not Aß42/40 ratio. Concordance between CSF biomarkers and amyloid-PET was higher in FTD patients compared to AD cases. None of the AD patients presented both negative Aß biomarkers. CONCLUSIONS: CSF Aß42/40 ratio significantly increased the diagnostic accuracy of CSF biomarkers. On the basis of our current and previous data, we suggest a flowchart to guide the use of biomarkers according to clinical suspicion due to the high PPV of both amyloid-PET and CSF analysis including Aß42/40, in cases of concordance between at least one biomarker and clinical diagnosis, performance of the other analysis could be avoided. A combination of both biomarkers should be performed to better characterize unclear cases. If the two amyloid biomarkers are both negative, an underlying AD pathology can most probably be excluded.