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. 2025 Jul 31;25(1):316.
doi: 10.1186/s12883-025-04325-y.

Cognitive impairment profile in patients with the m.3243A> G variant in mitochondrial DNA

Satu Winqvist  1 , Mikko Kärppä  1   2   3 , Jukka S Moilanen  2   3   4 , Kari Majamaa  5   6   7   8
Affiliations

Cognitive impairment profile in patients with the m.3243A> G variant in mitochondrial DNA

Satu Winqvist et al. BMC Neurol. .

Abstract

Background: The m.3243A>G variant in mitochondrial DNA is associated with a wide spectrum of clinical features ranging from asymptomatic subjects to severely symptomatic patients. Cognitive involvement is one of the clinical features, but its severity and frequency are not properly known. Here we describe neuropsychological features associated with m.3243 A > G.

Methods: We studied 45 adult patients with m.3243 A > G and 45 healthy subjects. Comprehensive neuropsychological test battery was applied. Cognitive impairment was defined, if at least five out of seven cognitive domains were impaired compared to matched controls. Major cognitive impairment was diagnosed, if the impairment was general across the domains.

Results: Sixteen patients (36%) with m.3243 A > G were diagnosed with cognitive impairment, and six of them (13%) had a major cognitive impairment. The median age at diagnosis of cognitive impairment was 53 years (range, 25-64). The profile consisted of impaired abstract reasoning, memory problems, motor function defects and executive problems. Executive functions were affected most, and verbal memory was affected the least. Higher variant heteroplasmy and more severe global phenotype were associated with cognitive impairment, whereas age and sex were not.

Conclusion: Cognitive impairment is found frequently in patients with m.3243 A > G, but major cognitive impairment is not common. The impairment affects all neuropsychological domains and no specific profile could be identified.

Keywords: Cognitive dysfunction; Heteroplasmy; Kaplan-Meier estimate; MELAS syndrome; Neuropsychological tests.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was approved by the Ethics Committee of the Medical Faculty, University of Oulu, and the study conforms with World Medical Association Declaration of Helsinki. Written informed consent has been obtained from each subject. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Neuropsychological test results of the 45 patients with m.3243A>G. The bars show 95 % confidence interval for the z score of the patients. Among the controls the mean z score in each test equals to 0 and standard deviation equals to 1
Fig. 2
Fig. 2
Kaplan-Meier plot for the probability of cognitive impairment in patients with m.3243 A > G. The event of interest was diagnosis of cognitive impairment and patients were censored at the age of death or at present age. One minus survival is plotted
See this image and copyright information in PMC

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