Neurofilament light chain and voice acoustics in dementia diagnosis (NAVAIDD): Protocol for a cohort study assessing the real-world diagnostic utility of blood and digital biomarkers in clinical settings

Background: The advent of disease modifying therapies for dementia has highlighted the need for simple, accessible and low-cost diagnostic tests. Blood and digital biomarkers increase accuracy in highly selected research populations. However, their real-world applicability for diverse clinical populations remains unknown. Objective: We will investigate the utility of plasma neurofilament light chain (NfL) and voice acoustic analysis in a multi-ethnic and multi-lingual population. We hypothesise that NfL and voice acoustic biomarkers will discriminate between individuals with a neurodegenerative diagnosis and those with non-neurodegenerative causes; abnormal biomarker findings will have high prognostic validity for clinical progression; and shorten the time to diagnosis and reduce costs. Methods: All adults presenting with a cognitive concern to outpatient and inpatient settings at a community-based healthcare network in Melbourne, Australia are eligible to participate. Plasma NfL and speech sample recordings are performed at baseline and functional status (modified Rankin Scale) is recorded. Clinical diagnostic consensus meetings are convened wherein baseline diagnostic class (neurodegenerative vs non-neurodegenerative), syndrome (diagnosis), and certainty (low, moderate, high) are confirmed with the clinician prior to and following disclosure of NfL to examine effect on clinical decision-making. Participants complete cognitive, functional and mood screens and speech sampling via 12-month follow-up phone call. Discussion: Blood and digital biomarkers are transforming the landscape of dementia diagnosis. Our study design allowing inclusion of people from diverse linguistic, cultural and racial backgrounds offers an opportunity to evaluate the utility of NfL and speech markers in real-world clinical settings. Trial registration: https//www.clinicaltrials.gov (NCT06339190), Apr 2024.