Derivation and utility of an Aβ-PET pathology accumulation index to estimate Aβ load
Johan Lilja et al.
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.