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. 2025 Feb;21(2):e14572.
doi: 10.1002/alz.14572.

Remote cognitive tests predict neurodegenerative biomarkers in the Insight 46 cohort

Martina Del Giovane  1   2 , Valentina Giunchiglia  1   3   4 , Ziyuan Cai  1   3 , Marguerite Leoni  1 , Rebecca Street  5 , Kirsty Lu  5 , Andrew Wong  6 , Maria Popham  6 , Jennifer M Nicholas  5   7 , William Trender  1 , Peter J Hellyer  3 , Thomas D Parker  1   2   5 , Heidi Murray-Smith  5 , David M Cash  5   8 , Josephine Barnes  5 , Carole H Sudre  6   9   10 , Paresh A Malhotra  1   2 , Sebastian J Crutch  5 , Marcus Richards  6 , Adam Hampshire  1   3 , Jonathan M Schott  5   6
Affiliations

Remote cognitive tests predict neurodegenerative biomarkers in the Insight 46 cohort

Martina Del Giovane et al. Alzheimers Dement. 2025 Feb.

Erratum in

Abstract

Background: Alzheimer's disease-related biomarkers detect pathology years before symptoms emerge, when disease-modifying therapies might be most beneficial. Remote cognitive testing provides a means of assessing early cognitive changes. We explored the relationship between neurodegenerative biomarkers and cognition in cognitively normal individuals.

Methods: We remotely deployed 13 computerized Cognitron tasks in 255 Insight 46 participants. We generated amyloid load and positivity, white matter hyperintensity volume (WMHV), whole brain and hippocampal volumes at age 73, plus rates of change over 2 years. We examined the relationship between Cognitron, biomarkers, and standard neuropsychological tests.

Results: Slower response time on a delayed recognition task predicted amyloid positivity (odds ratio [OR] = 1.79, confidence interval [CI]: 1.15, 2.95), and WMHV (1.23, CI: 1.00, 1.56). Brain and hippocampal atrophy rates correlated with poorer visuospatial performance (b = -0.42, CI: -0.80, -0.05) and accuracy on immediate recognition (b = -0.01, CI: -0.012, -0.001), respectively. Standard tests correlated with Cognitron composites (rho = 0.50, p < 0.001).

Discussion: Remote computerized testing correlates with standard supervised assessments and holds potential for studying early cognitive changes associated with neurodegeneration.

Highlights: 70% of the Online 46 cohort performed a set of remote online cognitive tasks. Response time and accuracy on a memory task predicted amyloid status and load (SUVR). Accuracy on memory and spatial span tasks correlated with longitudinal atrophy rate. The Cognitron tasks correlated with standard supervised cognitive tests. Online cognitive testing can help identify early AD-related memory deficits.

Keywords: Alzheimer's disease; Insight 46; amyloid; biomarkers; computerized cognitive testing; dementia; memory; neurodegeneration.

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Conflict of interest statement

A.H. is owner/director of H2 Cognitive Designs Ltd and Future Cognition Ltd, which produce online assessment technology and provide online survey data collection for third parties. P.H. is founder and director of H2 Cognitive Designs LTD, which develops and markets online cognitive tests. W.T. is an employee of H2 Cognitive Designs LTD. PM is lead for an NIHR‐funded trial with drug/placebo provided by Takeda Pharmaceuticals and sits on the Data Monitoring Committee for a trial being carried out by Johnson and Johnson. P.M. is vice chair of the Alzheimer's Society Research Strategy Council, and NIHR Specialty Lead for Dementia and Neurodegeneration, Research Delivery Network. He is also an independent member of a data monitoring committee. C.S. is a scientific BrainKey scientific advisor, part of MONAI advisory board. D.C. is chair of the Alzheimer's Association Neuroimaging professorial interest area and a member of the Scientific Programming Committee of the Alzheimer's Association. He also reports grants from the National Institute of Health. J.B. is an NFRFT 2024 Application Stage Expert Panel, director of SENBOX and Chair of Faculty Research Degrees Committee at University College London. J.M.S. is the Chief Medical Officer of Alzheimer's Research UK and clinical advisor at the UK Dementia Research Institute. He reports grants from the NIHR, LifeArc Foundation, and the British Hearth Foundation.

Figures

FIGURE 1
FIGURE 1
Recruitment flowchart.
FIGURE 2
FIGURE 2
Top: Illustrations of the Cognitron tasks. Bottom: Network plot showing clustering of the primary task scores, and the cognitive domains measured. The colors of the connecting lines indicate the 5 components derived from the PCA. A smaller distance and higher opacity of the connecting line indicate a stronger correlation. PCA, principal component analysis.
FIGURE 3
FIGURE 3
PCA applied to the Cognitron summary scores. Top: Scree plot showing eigenvalues (components extracted based on eigenvalues > 1). Bottom: Loadings of the Cognitron summary scores onto the derived cognitive components. PCA, principal component analysis.
FIGURE 4
FIGURE 4
Top: Density plots showing performance differences on the Objects delayed recognition task (accuracy and RT scores) between the amyloid positive and negative groups. Bottom: Association between SUVR and the Objects delayed recognition task (accuracy and RT scores). RT, reaction time; SUVR, standard uptake value ratio.
FIGURE 5
FIGURE 5
Scatter plots showing the associations between the Cognitron tasks and the biomarkers of AD, white matter pathology and neurodegeneration. The values represent the predicted outcomes from the regression models, adjusted for the included covariates (i.e., childhood cognitive abilities and total intracranial volume). AD, Alzheimer's disease.
FIGURE 6
FIGURE 6
Plots showing the association between: (A) the Cognitron composite score generated from the tasks which predicted the imaging biomarkers and the Insight 46 total composite score, (B) the Cognitron composite score generated from the tasks which predicted the imaging biomarkers and the PACC, and (C) the Cognitron memory composite score and the Insight 46 standard memory composite score. One participant had notably low Cognitron and Insight 46 memory composite scores, but excluding them from the analysis did not affect the statistical results. PACC, Preclinical Alzheimer cognitive composite.
See this image and copyright information in PMC

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