Amyloid-β PET Classification on Cognitive Aging Stages Using the Centiloid Scale

Propose: This study aims to explore the use of the Centiloid (CL) method in amyloid-beta PET quantification to evaluate distinct cognitive aging stages, investigating subjects' mismatch classification using different cut-points for amyloid-beta positivity. Procedures: The CL equation was applied in four groups of individuals: SuperAgers (SA), healthy age-matched controls (AC), healthy middle-aged controls (MC), and Alzheimer's disease (AD). The amyloid-beta burden was calculated and compared between groups and quantitative variables. Three different cut-points (Jack CR, Wiste HJ, Weigand SD, et al., Alzheimer's Dement 13:205-216, 2017; Salvado G, Molinuevo JL, Brugulat-Serrat A, et al., Alzheimer's Res Ther 11:27, 2019; and Amadoru S, Dore V, McLean CA, et al., Alzheimer's Res Ther 12:22, 2020) were applied in CL values to differentiate the earliest abnormal pathophysiological accumulation of A beta and the established A beta pathology. Results: The AD group exhibited a significantly increased A beta burden compared to the MC, but not AC groups. Both healthy control (MC and AC) groups were not significantly different. Visually, the SA group showed a diverse distribution of CL values compared with MC; however, the difference was not significant. The CL values have a moderate and significant relationship between A beta visual read, RAVLT DR and MMSE. Depending on the cut-point used, 10 CL, 19 CL, or 30 CL, 7.5% of our individuals had a different classification in the A beta positivity. For the AC group, we obtained about 40 to 60% of the individuals classified as positive. Conclusion: SuperAgers exhibited a similar A beta load to AC and MC, differing in cognitive performance. Independently of cut-point used (10 CL, 19 CL, or 30 CL), three SA individuals were classified as A beta positive, showing the duality between the individual's clinics and the biological definition of Alzheimer's. Different cut-points lead to A beta positivity classification mismatch in individuals, and an extra care is needed for individuals who have a CL value between 10 and 30 CL.

Automated summary

This study utilized the Centiloid method to classify subjects using different amyloid-beta positivity cut-points, revealing significantly increased A beta burden in the Alzheimer's disease group compared to healthy controls. Different cut-points resulted in classification mismatch in amyloid-beta positivity.