TAS Test: Online Motor-cognitive Tests for Early Detection of Alzheimer's Disease (TASTest)

TAS Test: Determining the Feasibility and Validity of Online Motor-cognitive Testing for Early Detection of Alzheimer's Disease

Global dementia prevalence is rising. Alzheimer's disease (AD), the most common cause, has devastating effects on people's quality of life. AD has a preclinical (pre-AD) period of 10-20 years when brain pathology silently progresses before any cognitive symptoms appear. Current tests for pre-AD are invasive, costly and unsuitable for screening at population level. Similar to screening for pre-diabetes and carcinoma in situ, it is important to detect AD at the preclinical stage in order to offer early interventions before the pathology progresses to the irrerversible degenerative stage. In the study, research will develop a new scalable test (TAS Test) by combining two innovative ideas: hand-movement tests to detect pre-AD >10 years before cognitive symptoms begin; and computer vision so people can "self-test" online using home computers. This unique approach builds on recent discoveries that hand-movement patterns change in pre-AD. The research team will use exquisitely precise computer vision methods to automatically analyse movement data from thousands of participants, and combine this with machine learning of overall motor-cognitive performance. The project team has access to 3 well-phenotyped cohorts, >10,000 existing participants and a cutting-edge assay for a blood AD biomarker, ptau181. The research team will develop a TAS Test algorithm to classify hand-movement and cognitive test data for pre-AD risk (p-taua181 levels) and determine TAS Test's precision to prospectively predict 5-year risks of cognitive decline and AD.

Study Overview

• Status: Recruiting
• Conditions: Dementia; Alzheimer Disease; Age-related Cognitive Decline
• Intervention / Treatment: Diagnostic test: Cognitive test scores, clinical diagnosis and blood biomarkers

Detailed Description

Sub-study 1: Cross-sectional study design: From two established cohorts with pre-existing datasets of up to 10 years of longitudinal cognitive, genetic and demographic data, the team will recruit 500 participants over 50 years old who are confirmed to have normal cognition. At baseline and months 3 and 6, the participants will be invited to complete TAS Test online at home, or in the research centre if preferred. The participants will also have a baseline blood test for ptau181 levels (and APOE4 if required). The research team will integrate movement data to develop a multivariable model that discriminates between pre-AD (positive p-tau181) and normal cognitive ageing (negative p-tau181).

Sub-study 2: Prospective 5-year cohort study design: The researchers will invite 10,000 adults from an established long-term (ISLAND Project) cohort to complete online tests at home: (i) TAS Test every 6 months, and (ii) Cambridge Neuropsychological Test Automated Battery (CANTAB) cognitive tests every 24 months. The prospective 'high risk' predictions of TAS Test at baseline will be validated against CANTAB scores, and also clinically (face to face gold standard consensus diagnosis of AD vs MCI vs normal) in a subsample of 300.

• Study Type: Observational
• Enrollment (Estimated): 3000

Contacts and Locations

• Study Contact: Name: A/Prof Alty, MD FRACP; Phone Number: +61 (0)3 36226 4273; Email: Jane.Alty@utas.edu.au

Study Locations

• Australia
  • Tasmania
    • Hobart, Tasmania, Australia, 7001
      • Recruiting
      • University of Tasmania
      • Contact: A/Prof Alty, MD FRACP; Phone Number: +61 (0)3 36226 4273; Email: Jane.Alty@utas.edu.au
      • Contact: Prof Vickers, PhD DSc; Phone Number: +61 3 6226 4808; Email: James.Vickers@utas.edu.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Currently focused on adults aged > 50 years in established cohort studies in Australia: ie participants from Tasmanian Healthy Brain Project, Healthy Brain and Ageing project or ISLAND Project.

Description

Inclusion Criteria: > 50years old

Exclusion Criteria: established diagnosis of dementia

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Develop and validate the optimal TAS Test protocol to detect pre-AD (p-tau 181 positivity)	Receiver Operating Characteristic (ROC) curves will be plotted against the positive p-tau181 cut-off to assess the sensitivity/specificity of TAS Test models to identify the pre-AD stage.	3 years
Prospectively validate TAS Test to predict risks of cognitive decline	Assess the sensitivity and specificity of TAS Test to predict cognitive trajectories (CANTAB scores) "stable" and "declining" using ROC curve analysis.	5 years
Prospectively validate TAS Test to predict risks of AD diagnosis	Multinomial logistic regression will estimate the (covariate adjusted) log-odds of being in each diagnostic category (AD, MCI and normal) at 5 years as predicted by baseline TAS Test results.	5 years

Collaborators and Investigators

• Sponsor: University of Tasmania
• Collaborators: National Health and Medical Research Council, Australia; University of Leeds; University of Sydney
• Investigators: Study Director: Prof Vickers, PhD DSc, University of Tasmania; Principal Investigator: A/Prof Bai, PhD MSc, University of Tasmania

Publications and helpful links

General Publications

• Alty J, Bai Q, Li R, Lawler K, St George RJ, Hill E, Bindoff A, Garg S, Wang X, Huang G, Zhang K, Rudd KD, Bartlett L, Goldberg LR, Collins JM, Hinder MR, Naismith SL, Hogg DC, King AE, Vickers JC. The TAS Test project: a prospective longitudinal validation of new online motor-cognitive tests to detect preclinical Alzheimer's disease and estimate 5-year risks of cognitive decline and dementia. BMC Neurol. 2022 Jul 18;22(1):266. doi: 10.1186/s12883-022-02772-5.

Helpful Links

• University profile for Principal Investigator

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: December 29, 2021
• First Submitted That Met QC Criteria: January 14, 2022
• First Posted (Actual): January 18, 2022

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: early detection; Artificial intelligence; pre-clinical; online tests
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: H0021660

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