1. Two-year prognostic utility of plasma p217+tau across the Alzheimer’s continuum
- Author
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Feizpour, A., Doré, V., Doecke, J. D., Saad, Z. S., Triana-Baltzer, G., Slemmon, R., Maruff, P., Krishnadas, N., Bourgeat, P., Huang, K., Fowler, C., Rainey-Smith, S. R., Bush, A. I., Ward, L., Robertson, J., Martins, R. N., Masters, C. L., Villemagne, V. L., Fripp, J., Kolb, H. C., Rowe, C. C., Feizpour, A., Doré, V., Doecke, J. D., Saad, Z. S., Triana-Baltzer, G., Slemmon, R., Maruff, P., Krishnadas, N., Bourgeat, P., Huang, K., Fowler, C., Rainey-Smith, S. R., Bush, A. I., Ward, L., Robertson, J., Martins, R. N., Masters, C. L., Villemagne, V. L., Fripp, J., Kolb, H. C., and Rowe, C. C.
- Abstract
Background: Plasma p217+tau has shown high concordance with cerebrospinal fluid (CSF) and positron emission tomography (PET) measures of amyloid- (A ) and tau in Alzheimer’s Disease (AD). However, its association with longitudinal cognition and comparative performance to PET A and tau in predicting cognitive decline are unknown. Objectives: 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 A (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 A (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: 153 cognitively unimpaired (CU) and 50 cognitively impaired (CI) individuals. Measurements: Baseline p217+tau Simoa assay 18F-MK6240 tau-PET and 18F-NAV4694 A -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 ( = −0.55, p < 0.001) and CDR-SB ( =0.61, p < 0.001) with an effect size similar to A Centiloid (MMSE = −0.48, p = 0.002; CDR-SB = 0.43, p = 0.004) and meta-temporal (MetaT) tau SUVR (MMSE: = −0.62, p < 0.001; CDR-SB: = 0.65, p < 0.001). In CU, only MetaT tau SUVR was significantly associated with change in AIBL-PACC ( = −0.22, p = 0.008). Screening pT+ CI participants into a trial could lead 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% biomarker test cost-saving assuming the p217+tau test cost one-fifth of a PET scan. In a trial requiring PET A+ or T+, p217+tau pre-screeni
- Published
- 2023