Concordance and Diagnostic Accuracy of [11C]PIB PET and Cerebrospinal Fluid Biomarkers in a Sample of Patients with Mild Cognitive Impairment and Alzheimer's Disease.

Abstract

Alzheimer's disease (AD) pathology can be quantified in vivo using cerebrospinal fluid (CSF) levels of amyloid-β1-42 (Aβ1-42), total-tau (t-tau), and phosphorylated tau (p-tau181p), as well as with positron emission tomography (PET) using [(11)C]Pittsburgh compound-B ([(11)C]PIB). Studies assessing concordance between these measures, however, have provided conflicting results. Moreover, it has been proposed that [(11)C]PIB PET may be of greater clinical utility in terms of identifying patients with mild cognitive impairment (MCI) who will progress to the dementia phase of AD. To determine concordance and classification accuracy of CSF biomarkers and [(11)C]PIB PET in a cohort of patients with MCI and AD. 68 patients (MCI, n = 33; AD, n = 35) underwent [(11)C]PIB PET and CSF sampling. Cutoffs of >1.41 ([(11)C]PIB), <450 pg/mL-and a more lenient cutoff of 550 pg/mL-(Aβ1-42), <6.5 (Aβ1-42/p-tau181p), and 1.14 (Aβ1-42/t-tau), were used to determine concordance. Logistic regression was used to determine classification accuracy with respect to stable MCI (sMCI) versus MCI who progressed to AD (pMCI). Concordance between [(11)C]PIB and Aβ1-42 was highest for sMCI (67%), followed by AD (60%) and pMCI (33%). Agreement was increased across groups using Aβ1-42 <550 pg/mL, or Aβ1-42 to tau ratios. Logistic regression showed that classification accuracy of [(11)C]PIB, between sMCI and pMCI, was superior to Aβ1-42 (73% versus 58%), Aβ1-42/t-tau (63%), and Aβ1-42/p-tau181p (65%). In the present study, [(11)C]PIB proved a better predictor of progression to AD in patients with MCI, relative to CSF measures of Aβ1-42 or Aβ1-42/tau. Discordance between PET and CSF markers for Aβ1-42 suggests they cannot be used interchangeably, as is currently the case.