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Lookup NU author(s): Dr Oksana Pogoryelova, Dr Rosabeth White, Jane Newman, Aye Moe, Dr Yi NgORCiD, Professor Grainne Gorman
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2026 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.Background: Primary mitochondrial disease is a group of genetic disorders caused by pathogenic variants in nuclear or mitochondrial DNA, often resulting in progressive neurodegeneration and cognitive decline. Current management is primarily supportive, though recent research offers hope for disease-modifying treatments in the future. Selecting appropriate therapeutic outcomes for clinical trials in mitochondrial diseases is challenging due to limited sensitivity to changes, small sample sizes, and the burden of study related activities. This study aims to identify an efficient choice of cognitive endpoints for translational research. Methods: This study compared digital cognitive assessments with traditional paper-based tools. It included two cohorts: the Newcastle cohort of 45 patients recruited from the mitochondrial clinic Newcastle upon Tyne (UK) and the KHENERGYZE clinical trial cohort of 27 patients recruited from four European countries. Patients in the Newcastle cohort underwent two conventional cognitive assessments (Addenbrooke's Cognitive Examination and Montreal Cognitive Assessment), along with two computerized tests (Cogstate and Test of Attentional Performance). Potential confounding factors were also assessed. Results: Both cohorts showed a high prevalence of moderate to severe perceived fatigue. Over 50% of patients showed reduced reaction times. Strong correlations were found between conventional and digital assessments. Several confounding factors such as education and employment were identified as influencing cognitive performance. Conclusions: The findings support the understanding of mitochondrial disease as a slowly progressive condition, where impaired cognitive function is evident even in patients in the absence of devastating CNS manifestations such as stroke-like episodes. Observed variability in cognitive performance may help detect meaningful changes over time.
Author(s): Pogoryelova O, Smeitink J, Renkema H, White R, Barton F, Lyon R, Newman J, Moe A, Ng YS, Gorman GS
Publication type: Article
Publication status: Published
Journal: Annals of Clinical and Translational Neurology
Year: 2026
Pages: epub ahead of print
Online publication date: 31/07/2026
Acceptance date: 14/06/2026
Date deposited: 18/08/2026
ISSN (electronic): 2328-9503
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1002/acn3.70463
DOI: 10.1002/acn3.70463
Data Access Statement: Anonymised, aggregated data underlying the findings of this study may be made available upon reasonable request to the corresponding author. Any request for data access will be reviewed by the relevant local institutional authorities to ensure compliance with participant consent and applicable local data protection policies. Data will only be shared in accordance with ethical guidelines and where appropriate approvals are in place.
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