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

Abstract

Background:

Alzheimer’s disease (AD) pathology can be quantified in vivo using cerebrospinal fluid (CSF) levels of amyloid-β_1-42 (Aβ_1-42), total-tau (t-tau), and phosphorylated tau (p-tau_181p), as well as with positron emission tomography (PET) using [¹¹C]Pittsburgh compound-B ([¹¹C]PIB). Studies assessing concordance between these measures, however, have provided conflicting results. Moreover, it has been proposed that [¹¹C]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.

Objective:

To determine concordance and classification accuracy of CSF biomarkers and [¹¹C]PIB PET in a cohort of patients with MCI and AD.

Methods:

68 patients (MCI, n = 33; AD, n = 35) underwent [¹¹C]PIB PET and CSF sampling. Cutoffs of >1.41 ([¹¹C]PIB), <450 pg/mL—and a more lenient cutoff of 550 pg/mL—(Aβ_1-42), <6.5 (Aβ_1-42/p-tau_181p), and 1.14 (Aβ_1-42/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).

Results:

Concordance between [¹¹C]PIB and Aβ_1-42 was highest for sMCI (67%), followed by AD (60%) and pMCI (33%). Agreement was increased across groups using Aβ_1-42 <550 pg/mL, or Aβ_1-42 to tau ratios. Logistic regression showed that classification accuracy of [¹¹C]PIB, between sMCI and pMCI, was superior to Aβ_1-42 (73% versus 58%), Aβ_1-42/t-tau (63%), and Aβ_1-42/p-tau_181p (65%).

Conclusion:

In the present study, [¹¹C]PIB proved a better predictor of progression to AD in patients with MCI, relative to CSF measures of Aβ_1-42 or Aβ_1-42/tau. Discordance between PET and CSF markers for Aβ_1-42 suggests they cannot be used interchangeably, as is currently the case.