Comparison of Diagnostic Performances Between Cerebrospinal Fluid Biomarkers and Amyloid PET in a Clinical Setting

Abstract

 The diagnostic performances of cerebrospinal fluid (CSF) biomarkers and amyloid positron emission tomography (PET) were compared by examining the association and concordance or discordance between CSF Aβ_1-42 and amyloid PET, after determining our own cut-off values for CSF Alzheimer’s disease (AD) biomarkers. Furthermore, we evaluated the ability of CSF biomarkers and amyloid PET to predict clinical progression. CSF Aβ_1-42, t-tau, and p-tau levels were analyzed in 203 individuals [27 normal controls, 38 mild cognitive impairment (MCI), 62 AD dementia, and 76 patients with other neurodegenerative diseases] consecutively recruited from two dementia clinics. We used both visual and standardized uptake value ratio (SUVR)-based amyloid PET assessments for analyses. The association of CSF biomarkers with amyloid PET SUVR, hippocampal atrophy, and cognitive function were investigated by linear regression analysis, and the risk of conversion from MCI to AD dementia was assessed using a Cox proportional hazards model. CSF p-tau/Aβ_1-42 and t-tau/Aβ_1-42 exhibited the best diagnostic accuracies among the CSF AD biomarkers examined. Correlations were observed between CSF biomarkers and global SUVR, hippocampal volume, and cognitive function. Overall concordance and discordance between CSF Aβ_1-42 and amyloid PET was 77% and 23%, respectively. Baseline positive CSF Aβ_1-42 for MCI demonstrated a 5.6-fold greater conversion risk than negative CSF Aβ_1-42 .  However, amyloid PET findings failed to exhibit significant prognostic value. Therefore, despite presence of a significant correlation between the CSF Aβ_1-42 level and SUVR of amyloid PET, and a relevant concordance between CSF Aβ_1-42 and amyloid PET, baseline CSF Aβ_1-42 better predicted AD conversion.