Neurofilament Light Chain And Voice Acoustic Analyses In Dementia Diagnosis

Recruiting

• Conditions: Neurodegenerative Diseases; Dementia

• Registration Number: NCT06339190
• Lead Sponsor: Monash University

Brief Summary

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.

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 Timeline

• Study Start: 2021-08-01
• Study First Submitted: 2023-09-21
• Status Verified: 2023-12
• Study First Submitted QC: 2024-03-29
• Last Update Submitted: 2024-03-29
• Study First Posted: 2024-04-01
• Last Update Posted: 2024-04-01
• Primary Completion: 2025-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

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

Exclusion Criteria

• Individuals not likely to live for 12 months

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Nfl correlation with neurodegeneration	Day 0	Plasma Nfl (pg/ml), estimated using Quanterix SIMOA HD-X

Secondary Outcome Measures

Name	Time	Method
Change in speech processing	Day 0 and 12-months	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).
Change in language processing	Day 0 and at 12-months	Recorded by a member of the research team using Redenlab software and assessed by a speech therapist using Natural Language Processing techniques.
Change in Direct Magnitude Estimation	Day 0 and at 12-months	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.

Trial Locations

Locations (2)

Box Hill Hospital; 🇦🇺 Box Hill, Victoria, Australia

Wantirna Health; 🇦🇺 Wantirna, Victoria, Australia