Cognitive Health in Ageing Register: Investigational and Observational Trial Studies in Dementia Research (CHARIOT): Prospective Readiness Cohort (PRO) Longitudinal Study

The aim of the study is to prospectively evaluate factors and markers associated with varying cognitive performance and longitudinal trajectories in individuals with differing levels of brain amyloid burden cross-sectionally as defined by PET imaging or Aβ42 CSF measurements (at CPSS1 screening), over a period of up to 12 years from CPSS1 screening. Two C2N assays, i.e. the plasma Precivity AD2 and Multi-Tau assays, will be used at baseline and end -of-study, to assess the amyloid and tau cerebral burden, shown to have a comparable performance to PET and CSF. The former simultaneously quantifies specific plasma amyloid beta and tau peptide concentrations to calculate the Aβ42/40 Ratio and p-tau217/np-tau217(p-tau217 Ratio). The ratios are combined into a proprietary statistical algorithm to calculate the Amyloid Probability Score 2 (APS2), a numerical value ranging from 0-100, that determines whether a patient is Positive (has high likelihood) or Negative (has low likelihood) for the presence of abnormally high brain amyloid plaques by amyloid PET scan.A negative (0 - 47) is consistent with a negative amyloid PET scan; it reflects a low likelihood of brain amyloid plaques and is therefore not consistent with a neuropathological diagnosis of Alzheimer's disease (AD). A positive (48 - 100) is consistent with a positive amyloid PET scan; it reflects a high likelihood of brain amyloid plaques, one of the neuropathological findings of Alzheimer's disease (AD). The Multi-Tau assay measures the individual values and rations of phosphorylated and non- phosphorylated p/non p-tau 217, p/non p-t181 and p/non p- t205. The presence of high amyloid and/or tau cerebral burden alone does not establish a clinical diagnosis of AD and the APS2 and multi-tau results will be interpreted in conjunction with other patient information and will be clinically correlated.