Performance of [18F]flutemetamol amyloid imaging against the neuritic plaque component of CERAD and the current (2012) NIA-AA recommendations for the neuropathologic diagnosis of Alzheimer's disease

Abstract

Introduction: Performance of the amyloid tracer [¹⁸F]flutemetamol was evaluated against three pathology standard of truth (SoT) measures including neuritic plaques (CERAD "original" and "modified" and the amyloid component of the 2012 NIA-AA guidelines).

Methods: After [¹⁸F]flutemetamol imaging, 106 end-of-life patients who died underwent postmortem brain examination for amyloid plaque load. Blinded positron emission tomography scan interpretations by five independent electronically trained readers were compared with pathology measures.

Results: By SoT, sensitivity and specificity of majority image interpretations were, respectively, 91.9% and 87.5% with "original CERAD," 90.8% and 90.0% with "modified CERAD," and 85.7% and 100% with the 2012 NIA-AA criteria.

Discussion: The high accuracy of either CERAD criteria suggests that [¹⁸F]flutemetamol predominantly reflects neuritic amyloid plaque density. However, the use of CERAD criteria as the SoT can result in some false-positive results because of the presence of diffuse plaques, which are accounted for when the positron emission tomography read is compared with the 2012 NIA-AA criteria.

Keywords: Alzheimer's disease; Amyloid PET; Autopsy; Diagnostic; Sensitivity; Specificity; Thal phasing; [18F]Flutemetamol.

Fig. 1

Percentage of normal/abnormal [¹⁸F]flutemetamol majority image interpretations by Thal phase. Green bar: negative scan interpretation; red bar: positive scan interpretation.

Fig. 2

Distribution of the selected population for the mean neuritic plaque score across the spectrum of amyloid pathology. ▼ = False-negative read. ^∗ = False-positive read. mCERAD_SOT = neuritic plaque density CERAD scoring (0–3). Note: several cases had borderline pathology, leading to lower reader confidence.