• Mejan-Fripp, Jurgen
• Villemagne, Victor
• Kolb, Hartmuth
• Robertson, Jo
• Ward, Larry
• Masters, Colin
• Martins, Ralph
• Huang, Kun
• Fowler, Christopher
• Feizpour, Azadeh
• Rowe, Christopher
• Doecke, James
• Bush, Ashley
• Rainey-Smith, Stephanie
• Saad, Ziad
• Triana-Baltzer, Gallen
• Slemmon, Randy
• Maruff, Paul
• Krishnadas, Natasha

Abstract

Background: Plasma p217+tau has shown high concordance with cerebrospinal fluid (CSF) and positron emission tomography (PET) measures of amyloid-β (Aβ) and tau. However, its association with longitudinal cognition and comparative performance to PET Aβ and tau in predicting cognitive decline are unknown.Objectives: This study aimed to evaluate whether p217+tau can predict the rate of cognitive decline observed over two-year average follow-up and compare this to prediction based on Aβ (18F-NAV4694) and tau (18F-MK6240) PET. We also explored the sample size required to detect a 30% slowing in cognitive decline in a 2-year trial and selection test cost using p217+tau (pT+) as compared to PET Aβ (A+) and tau (T+) with and without p217+tau pre-screening.Design: A prospective observational cohort study.Setting: Participants of the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL) and Australian Dementia Network (ADNeT).Participants: A total of 153 cognitively unimpaired (CU) and 50 cognitively impaired (CI) individuals.Measurements: Baseline p217+tau SIMOA assay, 18F-MK6240 tau-PET and 18F-NAV4694 Aβ-PET with neuropsychological follow-up (MMSE, CDR-SB, AIBL-PACC) over 2.4 ± 0.8 years.Results: In CI, p217+tau was a significant predictor of change in MMSE (β = -0.55, p < 0.001) and CDR-SB (β =0.61, p < 0.001) with an effect size similar to Aβ Centiloid (MMSE β = -0.48, p = 0.002; CDR-SB β = 0.43, p = 0.004) and MetaT tau SUVR (MMSE: β = -0.62, p < 0.001; CDR-SB: β = 0.65, p < 0.001). In CU, only MetaT tau SUVR was significantly associated with change in AIBL-PACC (β = -0.22, p = 0.008). Screening p217+tau positive (pT+) CI participants into a trial led to 24% reduction in sample size compared to screening with PET for A+ and 6-13% compared to screening with PET for T+ (different regions). This would translate to an 81-83% test cost-saving assuming the p217+tautest cost one-fifth of a PET scan. In a trial requiring PET A+ or T+, p217+tau pre-screening followed by PET in those who were pT+ would cost more in the CI group, compared to 30-38% test cost-saving in the CU.Conclusions: Substantial cost reduction can be achieved using p217+tau alone to select participants with MCI or mild dementia for a clinical trial designed to slow cognitive decline over two years, compared to participant selection by PET. In pre-clinical trials, p217+tau provides significant cost-saving if used as a pre-screening measure for PET A+ or T+ but in MCI/mild dementia cohort trials this may add to cost both in testing and in the increased number of participants needed for testing.

Topics

• tomography
• aging
• chemical ionisation