Toggle Main Menu Toggle Search

Open Access padlockePrints

Cognitive deficits in adult m.3243A>G- and m.8344A>G-related mitochondrial disease: Importance of correcting for baseline intellectual ability

Lookup NU author(s): Dr Heather MooreORCiD, Dr Thomas Kelly, Alexandra Bright, Dr Andrew Schaefer, Dr Alasdair Blain, Professor Robert Taylor, Professor Bobby McFarlandORCiD, Emeritus Professor Doug Turnbull, Professor Grainne Gorman



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Objective - To determine the cognitive profile of adult patients with mitochondrial disease, and the effect of disease severity on cognition.Methods - Using a prospective case-control design, we compared cognition of patients to normative data and to matched controls, assessed three times over 18 months. Forty-nine patients with m.3243A>G (N = 36) and m.8344A>G (N = 13) mtDNA mutations and 32 controls, matched by age (±5 years) and premorbid cognition (±10 WTAR FSIQ points), participated. Participants completed neuropsychological assessments of general cognition (WAIS-IV), executive function (D-KEFS), and memory (WMS-IV). Potential predictors of cognition were explored.Results - Patients show mild-to-moderate premorbid cognitive impairment, but substantial impairment in current general cognition and distinct domains, including verbal comprehension, perceptual reasoning, working memory, processing speed, and memory retrieval. Executive dysfunction may be caused by slower decision-making. Patients performed worse than controls, except on memory tasks, indicating intact memory, when premorbid cognition is controlled for. Premorbid cognition and disease severity were consistent predictors of cognition in patients; however, cognitive decline appears slow and is unlikely in the short-term, when other disease-specific factors remain stable.Interpretation - Patients should be monitored to facilitate early identification of a complex profile of cognitive deficits and individuals with higher disease burden should be followed up more closely. On development of cognitive difficulties, appropriate compensatory strategies should be determined through in-depth assessment. Using strategies such as slower presentation of information, multiple modes of presentation, active discussion to aid understanding and decision-making, and use of memory aids, may ameliorate difficulties.

Publication metadata

Author(s): Moore HL, Kelly T, Bright A, Field RH, Schaefer AM, Blain AP, Taylor RW, McFarland R, Turnbull DM, Gorman GS

Publication type: Article

Publication status: Published

Journal: Annals of Clinical and Translational Neurology

Year: 2019

Volume: 6

Issue: 5

Pages: 826-836

Print publication date: 01/05/2019

Online publication date: 27/03/2019

Acceptance date: 17/12/2018

Date deposited: 06/06/2019

ISSN (electronic): 2328-9503

Publisher: Wiley


DOI: 10.1002/acn3.736


Altmetrics provided by Altmetric


Funder referenceFunder name
Wellcome Trust