Neurofilament Light Chain And Voice Acoustic Analyses In Dementia Diagnosis (NAVAIDD)

A Blood Test for Dementia? A Cohort Study to Assess the Diagnostic Utility of Plasma Neurofilament Light Chain Protein in All-cause Dementia

This cohort study aims to determine if a blood test can aid with diagnosing dementia in anyone presenting with cognitive complaints to a single healthcare network. The investigators will measure levels of a brain protein, Neurofilament light chain (Nfl), and assess changes in language using speech tests.

Participants will have a single blood test and speech test, and will be followed up at 12-months to complete questionnaires and cognitive scales over the phone. The speech test will also be completed again at 12-months.

Individuals at risk of a Fronto-temporal dementia syndrome will be eligible to complete optional genetic testing involving an 'at home' saliva sample.

Study Overview

• Status: Recruiting
• Conditions: Neurodegenerative Diseases; Dementia
• Intervention / Treatment: Diagnostic test: Venepuncture

Detailed Description

Problem: There is no "gold-standard test" to detect all forms of dementia. People can present with subtle changes that are missed on standard cognitive screening tests, which are not designed for people whose first language is not English or from diverse cultural and educational backgrounds. State-of-the art brain imaging is only available to Australians living in large urban centres, further entrenching health care inequities. The lack of validated diagnostic tests and pathways causes diagnostic delays, increases patient and caregiver stress. Therapies are on the horizon for many forms of dementia - not only Alzheimer's disease - meaning that the lack of identification of simple dementia diagnostic biomarkers represents a critical knowledge gap.

Mission: New technologies now allow us to test abnormal brain protein levels in a routine peripheral blood test, record a voice sample to analyse its acoustics and reveal brain disease, and perform "mail-out" genetic tests using a simple saliva sample. The levels of a brain derived blood protein, neurofilament light chain (NfL), will be estimated and natural language processing and acoustic analysis will be measured in all patients presenting with cognitive complaints to a single healthcare network servicing 1 million ethnically and culturally diverse Australians. Researchers will investigate the utility of early genetic testing for those at high risk of a genetic cause for their disease. They will use these data to develop diagnostic pathways, leveraging existing collaborations to develop future screening programs. Early to mid-career researchers will be supported to translate new technologies into clinical practice in the shortest practicable time-frame.

Significance: Accessible and cost effective tests will inform new pathways to dementia diagnosis. This will transform the dementia landscape, shortening time to diagnosis, increasing diagnostic certainty, and allowing more Australians access to appropriate care, education, and future therapies.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Prof. Amy Brodtmann, MBBS, FRACP, PhD, FANZAN; Phone Number: 03 9094 9540; Email: amy.brodtmann@monash.edu
• Study Contact Backup: Name: Svetlana Ivanic, BSc(Hons); Email: svetlana.ivanic@monash.edu

Study Locations

• Australia
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Recruiting
      • Box Hill Hospital
      • Contact: Svetlana Ivanic; Email: svetlana.ivanic@monash.edu
    • Wantirna, Victoria, Australia, 3152
      • Recruiting
      • Wantirna Health
      • Contact: Sarah Shue

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study cohort will include any individual of all ages, ethnicities, identities and genders. This is to ensure that the findings are generalisable to other national healthcare networks and to provide maximum information on the utility of using blood-biomarker estimation in real-world clinical settings

Description

Inclusion Criteria:

• All patients presenting to Eastern Health services with a cognitive complaint or potential neurodegenerative disorder

Exclusion Criteria:

• Prognosis <12 months
• No cognitive complaint
• Patients not involved within the single healthcare network

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline NfL level	Plasma Nfl (pg/ml), estimated using Quanterix SIMOA HD-X	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in speech processing	Staff and/or self administered using Redenlab software and analysed by speech pathologist for acoustic measures of timing (e.g., pause length (seconds) in reading and monologue tasks), vocal control (e.g., fundamental frequency (hertz) and loudness variation (decibel) from vowel and monologue), and vocal quality (e.g., dysphonia measures derived from sustained vowel).	Day 0 and 12-months
Change in language processing	Recorded by a member of the research team using Redenlab software and assessed by a speech therapist using Natural Language Processing techniques.	Day 0 and at 12-months
Change in Direct Magnitude Estimation	Perceptual rating of speech using Redenlab software; measuring intelligibility (i.e ability to be understood) and naturalness (deviation from healthy norm) of speech. Assessed by a speech therapist on a scale from 0 to 100; 0 indicates none of the speech is intelligible/natural, 100 indicates all the speech is intelligible/natural.	Day 0 and at 12-months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale	Functional screen; assessed by member of the research team based on clinical notes. Assessed as change from baseline. Scores ranging from 0-5, with higher scores indicating greater disability.	Day 0 and at 12-months
Montreal Cognitive Assessment score	Cognitive screen; staff administered via telephone. Scores include overall MoCA score (0-22) and Memory Index Score (0-15), greater scores indicate greater cognition.	At 12-months
Hospital Anxiety and Depression Scale score	Mood screen; staff administered via telephone. Scores include a total depression score (0-21) and total anxiety score (0-21); grouped according to normal (0-7), Borderline abnormal (8-10) and Abnormal (11-21).	At 12-months
Clinical Global Impression score	Global rating of improvement/change; staff administered via telephone. Scored on a 7 point scale, scores closer to 0 indicative of greater improvement and scores closer to 7 representing much worse).	At 12-months
WHO Disability Assessment 12-item telephone interview score	Functional screen, staff administered via telephone. Scored as an overall percentage (%) disability, higher scores indicating less function.	At 12-months
WHO Disability Assessment 36-item self report score	Functional screen, self administered. Scored as an overall percentage (%) disability, higher scores indicating less function.	At 12-months
DNA sample for testing known pathogenic dementia mutations	Self-administered saliva sample; Testing using Invitae Fronto-temporal dementia and AD panel: C9orf72, CHCHD10, CHMP2B, DCTN1, FUS, GRN, HNRNPA2B1, MAPT, SQSTM1, TARDBP, TBK1, TREM2, UBQLN2, VCP	Anytime before 12-months

Collaborators and Investigators

• Sponsor: Monash University
• Collaborators: University of Melbourne; Wake Forest University; Invitae Corporation; Eastern Health; Deakin University; The Florey Institute of Neuroscience and Mental Health; Redenlab
• Investigators: Principal Investigator: Prof. Amy Brodtmann, MBBS, FRACP, PhD, FANZAN, Monash University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: September 21, 2023
• First Submitted That Met QC Criteria: March 29, 2024
• First Posted (Actual): April 1, 2024

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 29, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Biomarker; Alzheimer's disease; Dementia; Neurodegeneration; Speech; Neurofilament light chain; Health care disparity
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Neurodegenerative Diseases
• Other Study ID Numbers: E21-006-72840

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No