The Journal of Prevention of Alzheimer’s Disease | July 5, 2023

Feizpour A, Doré V, Doecke JD, Saad ZS, Triana-Baltzer G, Slemmon R, Maruff P, Krishnadas N, Bourgeat P, Huang K, Fowler C, Rainey-Smith SR, Bush AI, Ward L, Robertson J, Martins RN, Masters CL, Villemagne VL, Fripp J, Kolb HC, Rowe CC.

J Prev Alzheimers Dis. 2023

https://doi.org/10.14283/jpad.2023.83

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 in Alzheimer’s Disease (AD). However, its association with longitudinal cognition and comparative performance to PET Aβ 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 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

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 meta-temporal (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 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.