The impact of tau‐PET in a selected memory clinic cohort: design and rationale of the TAP‐TAU study

Abstract Background Tau‐PET is a diagnostic tool with high sensitivity and high specificity for discriminating Alzheimer Disease (AD) dementia from other neurodegenerative disorders in well‐controlled research environments. The role of tau‐PET in “real‐world” clinical practice, however, remains to be established. We hypothesize that tau‐PET will lead to some changes of the pre‐PET clinical diagnosis and will improve diagnostic certainty and patient management in patients with considerable diagnostic uncertainty. The aim of the TAP‐TAU study is therefore to investigate the impact of tau‐PET in clinical practice. Method The TAP‐TAU study, is a prospective, longitudinal multi‐center study in 300 patients (≥50 years old) with prodromal or mild dementia recruited in six Dutch memory clinics. Patients are eligible if diagnostic certainty is <85% after routine dementia screening and if the differential diagnosis includes AD. For example, patients i) are suspected of having mixed pathology (e.g., AD and vascular pathology), and/or ii) have an atypical clinical presentation, and/or iii) show conflicting or inconclusive outcomes on other biomarkers (e.g., magnetic resonance imaging or cerebrospinal fluid). Participants will undergo a [ 18 F]flortaucipir tau‐PET scan, blood‐based biomarker sampling, and fill out patient wellbeing surveys (Figure 1). The primary outcome measures are change (pre‐ versus post‐ tau‐PET) in diagnosis, diagnostic certainty, patient management and patient wellbeing. Secondary outcome measures are head‐to‐head comparisons between tau‐PET and less‐invasive, lower cost and more scalable diagnostic tools such as novel blood‐based biomarkers and artificial intelligence based classifiers. A control group will be formed by patients who do not wish to undergo any study intervention (n=60). All participants will be followed for a year in the memory clinic. Result The first participants will be enrolled in March 2024. Conclusion In TAP‐TAU, we will investigate the added clinical value of tau‐PET in a real‐world clinical setting, including memory clinic patients with limited diagnostic certainty after routine work‐up. Findings of our study may contribute to recommendations regarding which patients may benefit most from assessment with tau‐PET. This study is timely in the dawning era of disease‐modifying treatments as vigilance concerning mixed pathologies and atypical presentations in the memory clinic population grows.