Derivation and utility of an Aβ-PET pathology accumulation index to estimate Aβ load
Antoine Leuzy, Johan Lilja, Christopher J. Buckley, Rik Ossenkoppele, Sebastian Palmqvist, Mark Battle, Gill Farrar, Dietmar R. Thal, Shorena Janelidze, Erik Stomrud, Olof Strandberg, Ruben Smith, Oskar Hansson
Objective To evaluate a novel Aβ-PET based quantitative measure (Aβ accumulation index [Aβ-index]), including the assessment of its ability to discriminate between subjects based on Aβ-status using visual-read, CSF Aβ42/Aβ40 and post-mortem neuritic-plaque burden as standards of truth.
Methods One thousand hundred twenty-one subjects (with and without cognitive impairment) scanned with Aβ-PET: Swedish BioFINDER, n = 392, [18F]flutemetamol; ADNI, n = 692, [18F]florbetapir; a phase-3 end-of-life study, n = 100, [18F]flutemetamol). The relationships between Aβ-index and standardized uptake values ratios (SUVR) from Aβ-PET were assessed. The diagnostic performance of Aβ-index and SUVR were compared when using visual reads, CSF Aβ42/Aβ40 and Aβ-histopathology as reference standards.
Results Strong associations were observed between Aβ-index and SUVR (R2, BioFINDER, 0.951; ADNI, 0.943, end-of-life, 0.916). Both measures performed equally well in differentiating Aβ-positive from Aβ-negative subjects, with AUCs of 0.979–0.991 to detect abnormal visual reads, AUCs of 0.961–0.966 to detect abnormal CSF Aβ42/40 and AUCs of 0.820–0.823 to detect abnormal Aβ-histopathology. Both measures also showed a similar distribution across post-mortem based Aβ-phases (based on anti-Aβ 4G8 antibodies). By comparison to models using visual-read alone, the addition of the Aβ-index resulted in a significant increase in AUC and a decrease in Akaike information criterion to detect abnormal Aβ-histopathology.
Conclusion The proposed Aβ-index showed a tight association to SUVR and carries an advantage over the latter in that it does not require the definition of regions of interest nor the use of MRI. Aβ-index may thus prove simpler to implement in clinical settings and may also facilitate the comparison of findings using different Aβ-PET tracers.
Classification of evidence This study provides Class III evidence that the Aβ accumulation index accurately differentiates Aβ-positive from Aβ-negative subjects when compared to Aβ-PET visual reads, CSF Aβ42/Aβ40 and Aβ-histopathology.