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-screening followed by PET in those who were pT+ would cost more in the CI group, compared to 26–38% biomarker 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 AD trials, p217+tau provides significant cost-saving if used as a pre-screening measure for PET A+ or T+ but in MCI/mild dementia trials this may add to cost both in testing and in the increased number of participants needed for testing.
RAS ID
62067
Document Type
Journal Article
Date of Publication
1-1-2023
Funding Information
Australian Federal Government / National Health and Medical Research Council / Enigma Australia / Open Access funding enabled and organized by CAUL and its Member Institutions
School
School of Medical and Health Sciences
Grant Number
NHMRC Numbers : APP1132604, APP1140853, APP1152623
Grant Link
http://purl.org/au-research/grants/nhmrc/1132604 http://purl.org/au-research/grants/nhmrc/1140853
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Publisher
Springer
Recommended Citation
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. (2023). Two-year prognostic utility of plasma p217+tau across the Alzheimer’s continuum. DOI: https://doi.org/10.14283/jpad.2023.83
Comments
Feizpour, A., Doré, V., Doecke, J. D., Saad, Z. S., Triana-Baltzer, G., Slemmon, R., . . . Rowe, C. C. (2023). Two-year prognostic utility of plasma p217+tau across the Alzheimer’s continuum. Journal of Prevention of Alzheimer's Disease, 10(4), 828-836. https://doi.org/10.14283/jpad.2023.83