TapTalkTest Project:Development of a Non-invasive Screening Test to Detect Risk of Alzheimer's Disease Pathology

Alzheimer Disease Clinical Trial

— TapTalkTest  

Official title:

TapTalkTest: Development of a Non-invasive Screening Test to Detect Risk of Alzheimer's Disease Pathology

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06114914
• Other study ID #: UTasmania
• Status: Enrolling by invitation
• Start date: August 1, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: November 2023
• Source: University of Tasmania
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This project aims to produce a solution for the rising incidence of dementia. This is particularly pertinent in Tasmania, Australia, with a rapidly ageing population and the oldest demographics of all Australian states. The team will develop TapTalk, a new screening test that detects risk of Alzheimer's disease (AD) pathology. TapTalk, will record a person's hand movements and speech patterns with a smartphone. Computer algorithms will learn which patterns of data are associated with AD pathology. This innovative test is based on: (i) emerging research that fine motor control required for hand and speech movements is sensitive to early AD pathology and (ii) the investigators' new machine learning methods.

Description:

This project aims to produce a solution for the rising incidence of dementia. This is particularly pertinent in Tasmania, with a rapidly ageing population. The investigators' will develop TapTalk, a new screening test that detects risk of Alzheimer's disease (AD) pathology. Accounting for 70% of all dementias, the brain pathology of AD progresses silently for more than 10 years before cognitive symptoms emerge (preclinical AD). It is possible to prevent 40% of dementia by modifying risk factors such as physical inactivity and smoking. However, the lack of a cost-effective screening tool means researchers and clinicians cannot target interventions, or recruit to drug trials, in early AD. Currently, cognitive tests lack sensitivity in preclinical AD, and specialist AD biomarker tests are invasive or costly.

The investigators will address the hypothesis: "Hand-speech movement patterns will detect the risk of Alzheimer's disease pathology in research and clinical cohorts" through three aims:

1. Develop and validate analytic algorithms for TapTalk by determining which combinations of hand-speech movement data most accurately detect preclinical AD

2. Develop smartphone capability for TapTalk and determine usability and validity

3. Prospectively validate TapTalk in people who have cognitive symptoms against gold-standard clinical diagnosis of Mild Cognitive Impairment (MCI) and AD dementia

AIM 1 Problem: Identify which combination of hand-speech tests will be most discriminatory.

Method: The investigators will develop software to video-record a 2-minute oral DDK (diadochokinesis) test, where participants make speech-like sounds repetitively e.g. pa-ta-ka. We already have software to collect hand movements (see TAS Test project). The research team will invite 500 ISLAND Project participants (>50 years old) with normal cognition to compete the hand-speech tests. All participants have provided blood samples for p-tau181 levels. This new assay quantifies AD pathology (using our ultrasensitive Simoa analyser) but the practicalities and cost of accessing the highly-specialist analytic equipment limit wide accessibility. We use ptau-181 as this is a highly predictive blood biomarkers of AD risk.

Analysis: The investigators will use deep neural networks to automatically track video key points (e.g. finger/thumb tips) and audio features (e.g. pa-ta-ka). A sliding window approach extracts measures (e.g. speed/rhythm) as input data for developing an algorithm that that classifies p-tau181 levels. Outcome: TapTalk protocol and algorithm.

AIM 2 Problem: Develop smartphone capabilities and age/cognitive status cut-offs Method We will develop a smartphone app. ISLAND Project participants (CANTAB cognitive tests every 24 months in-kind) will be invited to complete TapTalk online every 12 months.

Analysis: Multi-level regression models will measure within-subject variability, and group differences on TapTalk and CANTAB at baseline, 12 and 24 months.

Outcome: An externally validated TapTalk algorithm that produces AD risk scores across age and cognitive ranges.

AIM 3 Problem: Validate TapTalk in people with cognitive symptoms. Method: The clinician researchers working at the Royal Hobart Hospital (RHH) will recruit 100 patients with cognitive symptoms (>3 months) from RHH acute medical/subacute units. The research assistant (RHHF funding requested) will complete a standard cognitive screening tool (MoCA) and smartphone TapTalk then invite patients to attend the new ISLAND cognitive clinic after discharge. This 'one-stop' interdisciplinary clinic provides bulk-billed neuropsychological and geriatrician, neurologist and physiotherapist assessments. The team will also recruit 100 consecutive patients referred to the clinic by their GPs and all patients will complete TapTalk.

Analysis: The accuracy of TapTalk and MoCA will be compared to diagnosis using ROC analysis.

Outcome: TapTalk prospectively clinically validated.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 1000
• Est. completion date: December 31, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

AIM 1 AND AIM 2 Eligibility criteria

Inclusion Criteria:

• Adults >50 years old who are participants in the ISLAND Project and who have provided a blood sample and have normal cognition and no persistent (>3 months) cognitive symptoms will be eligible.

Exclusion Criteria:

• Impaired cognition, defined by a validated cut-off score >1.5 SD above the mean total errors adjusted for age and gender on the Paired Associates Learning sub-test of CANTAB.

AIM 3 Eligibility criteria Inclusion Criteria: >3 months of persistent cognitive symptoms (patient- or family-reported) and >50 years old.

Exclusion criteria: Acutely unwell, significant impairment of hand function, or known diagnosis of mild cognitive impairment (MCI) or dementia.

Related Conditions & MeSH terms

• Alzheimer Disease
• Dementia
• Movement Disorders
• Speech Disorders

Intervention

Diagnostic Test:
• Tap Talk online program
Online hand and speech motor testing

Locations

Country	Name	City	State
Australia	University of Tasmania	Hobart	Tasmania

Sponsors (1)

Lead Sponsor	Collaborator
University of Tasmania

Country where clinical trial is conducted

Australia, 

References & Publications (5)

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. — View Citation

Alty J, Lawler K, Salmon K, McDonald S, Stuart K, Cleary A, Ma J, Rudd K, Wang X, Chiranakorn-Costa S, Collins J, Merl H, Lin X, Vickers JC. A new one-stop interdisciplinary cognitive clinic model tackles rural health inequality and halves the time to diagnosis: Benchmarked against a national dementia registry. Int J Geriatr Psychiatry. 2023 Aug;38(8):e5988. doi: 10.1002/gps.5988. — View Citation

Bartlett L, Bindoff A, Doherty K, Kim S, Eccleston C, Kitsos A, Roccati E, Alty J, King AE, Vickers JC. An online, public health framework supporting behaviour change to reduce dementia risk: interim results from the ISLAND study linking ageing and neurodegenerative disease. BMC Public Health. 2023 Sep 29;23(1):1886. doi: 10.1186/s12889-023-16805-2. — View Citation

Huang G, Li R, Bai Q, Alty J. Multimodal learning of clinically accessible tests to aid diagnosis of neurodegenerative disorders: a scoping review. Health Inf Sci Syst. 2023 Jul 22;11(1):32. doi: 10.1007/s13755-023-00231-0. eCollection 2023 Dec. — View Citation

Wang X, St George RJ, Bindoff AD, Noyce AJ, Lawler K, Roccati E, Bartlett L, Tran SN, Vickers JC, Bai Q, Alty J. Estimating presymptomatic episodic memory impairment using simple hand movement tests: A cross-sectional study of a large sample of older adults. Alzheimers Dement. 2023 Jul 30. doi: 10.1002/alz.13401. Online ahead of print. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Classification accuracy for blood biomarker of Alzheimer's disease, ptau181 in adults without cognitive symptoms	Area under a receiver operating characteristic (ROC) curve - AUC	2024
Primary	Odds ratio of cognitive decline in adults without cognitive symptoms	Mixed effects logistic regression will be used to estimate the odds of a participant being confirmed as 'declining' at time T2 (24 months) conditioned on TapTalk score at time T1 (12 months), where the main measure of cogitive function is the CANTAB paired associate learning (PAL) test.	2025
Primary	Classification accuracy for prospectively predicting risk of MCI and AD in adults with cognitive symptoms	The investigators will calculate AUC for TapTalk and MoCA. 95% confidence intervals will be obtained using bootstrapping. Covariates may include age, gender, APOE4, years of education, and handedness. The investigators will estimate cut-off scores for TapTalk and MoCA to differentiate between cognitively unimpaired vs MCI, and between cognitively unimpaired vs AD using the Youden index to optimise the trade-off between sensitivity and specificity. Classification accuracy (sensitivity and specificity) using these cut-offs will be compared using McNemar's test.	2025

External Links

•   ISLAND Clinic - a one-stop cognitive assessment clinic that we will recruit participants from in Aim 3
•   ISLAND Project - 10-year prospective cohort study that we will recruit participants from in Aims 1 and 2