Derivation and utility of an Aβ-PET pathology accumulation index to estimate Aβ load

<p><b>Abstract</b></p> <p><b>Objective: </b>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 <i>post-mortem</i> neuritic-plaque burden as standards of truth.</p> <p><b>Methods: </b>1121 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.</p> <p><b>Results:</b> 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 <i>post-mortem </i>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.</p> <p><b>Conclusions</b><b>:</b> 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.</p>