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

This study aims to explore the use of the Centiloid (CL) method in amyloid-β PET quantification to evaluate distinct cognitive aging stages, investigating subjects' mismatch classification using different cut-points for amyloid-β positivity.

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-β 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; Salvadó G, Molinuevo JL, Brugulat-Serrat A, et al., Alzheimer's Res Ther 11:27, 2019; and Amadoru S, Doré 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 Aβ and the established Aβ pathology.

The AD group exhibited a significantly increased Aβ 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 Aβ 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 Aβ positivity. For the AC group, we obtained about 40 to 60% of the individuals classified as positive.

SuperAgers exhibited a similar Aβ 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 Aβ positive, showing the duality between the individual's clinics and the biological definition of Alzheimer's. Different cut-points lead to Aβ positivity classification mismatch in individuals, and an extra care is needed for individuals who have a CL value between 10 and 30 CL.