Estimating presymptomatic episodic memory impairment using simple hand movement tests: A cross-sectional study of a large sample of older adults

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Estimating presymptomatic episodic memory impairment using simple hand movement tests: A cross-sectional study of a large sample of older adults

Xinyi Wang, Rebecca J. St George, Aidan D. Bindoff, Alastair J. Noyce, Katherine Lawler, Eddy Roccati, Larissa Bartlett, Son N. Tran, James C. Vickers, Quan Bai, Jane Alty

First published: 30 July 2023

https://doi.org/10.1002/alz.13401

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Abstract

INTRODUCTION

Finding low-cost methods to detect early-stage Alzheimer's disease (AD) is a research priority for neuroprotective drug development. Presymptomatic Alzheimer's is associated with gait impairment but hand motor tests, which are more accessible, have hardly been investigated. This study evaluated how home-based Tasmanian (TAS) Test keyboard tapping tests predict episodic memory performance.

METHODS

1169 community participants (65.8 ± 7.4 years old; 73% female) without cognitive symptoms completed online single-key and alternate-key tapping tests and episodic memory, working memory, and executive function cognitive tests.

RESULTS

All single-key (R²_adj = 8.8%, ΔAIC = 5.2) and alternate-key (R²_adj = 9.1%, ΔAIC = 8.8) motor features predicted episodic memory performance relative to demographic and mood confounders only (R²_adj = 8.1%). No tapping features improved estimation of working memory.

DISCUSSION

Brief self-administered online hand movement tests predict asymptomatic episodic memory impairment. This provides a potential low-cost home-based method for stratification of enriched cohorts.

Highlights

• We devised two brief online keyboard tapping tests to assess hand motor function.
• 1169 cognitively asymptomatic adults completed motor- and cognitive tests online.
• Impaired hand motor function predicted reduced episodic memory performance.
• This brief self-administered test may aid stratification of community cohorts.

1 BACKGROUND

Dementia prevalence is predicted to triple to more than 150 million globally by 2050.^{1, 2} Most cases are caused by Alzheimer's disease (AD), which has a 10- to 20-year presymptomatic period of “silent” brain pathology (amyloid beta and tau deposition) before episodic memory symptoms emerge.³ To reduce dementia prevalence, there is an urgent need to identify at-risk individuals for early interventions. Up to 40% of dementia cases are attributable to modifiable risk factors,⁴ and the recent emergence of monoclonal therapies for AD may be most efficacious earlier in the disease course.^{5, 6} Dementia prevention and drug development are hindered by the lack of accessible, cost-effective tests to identify “at-risk” cohorts for specialist assessments, early recruitment to clinical trials, and targeted interventions. Current methods, such as neuropsychological assessments, blood- and cerebrospinal fluid (CSF)-based biomarkers, and positron emission tomography (PET) scans are too expensive, time-consuming, or invasive.³

Motor analysis holds strong potential to identify people at risk of AD. Gait slows down, with less rhythmic stepping, about 10 years before dementia diagnosis,⁷ but the need for specialist movement-sensing equipment and fall risk are barriers for translation to a population-level test. Though less explored than gait, hand motor function also declines in presymptomatic AD and has the advantage of accessible assessments through computer keyboards.⁸ Two recent studies found slower and less rhythmic tapping features in mild cognitive impairment (MCI) and AD, but both required laboratory-based equipment.^{9, 10} In 2019, Mollica et al. evaluated hand motor function in 72 older adults and found the speed and rhythm of repeatedly tapping a single computer key discriminated those with presymptomatic AD (n = 20, CSF Aβ-positive) from those with negative CSF biomarkers (n = 37).⁸ These promising findings have not yet been replicated in other at-risk groups or in larger samples.

This study builds upon Mollica et al.’s study by designing a self-administered keyboard tapping test to measure hand motor function at home. We aimed to evaluate (i) whether a single-key tapping test would help identify subtly impaired cognitive performance in episodic memory in a large community cohort of older cognitively asymptomatic adults, over and above a model that includes age, education, sex, level of education, anxiety, and depression; (ii) how a single-key motor performance test would compare with a more challenging alternate-key tapping test (based on the Bradykinesia Akinesia Incoordination [BRAIN] tap test¹¹); and (iii) which combination of motor features would best predict cognitive performance.

We hypothesized that impaired hand motor performance (defined as slower tapping frequency, arrhythmia, inaccurate target, or prolonged dwell time on each key) would associate with impairments in episodic memory but not in cognitive domains less sensitive to early AD (working memory, executive dysfunction)¹² and that the alternate-key test would have a stronger association due to greater cognitive loads required for key switching.

 

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