Mitochondrial DNA Mutations and Cognition: A Case-Series Report

Inczédy-Farkas, Gabriella; Trampush, Joey W.; Forintos, Dóra Perczel; Beech, Danielle; Andrejkovics, Mónika; Varga, Zsófia; Remenyi, Viktoria; Bereznai, Benjámin; Gál, Anikó; Molnár, Mária Judit

doi:10.1093/arclin/acu016

Cited by 33 publications

(17 citation statements)

References 20 publications

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“…Many patients with primary mtDNA mutations demonstrated pronounced cognitive deficits quite similar to those commonly seen in AD [69], which supports a critical role of mtDNA in proper cognitive function. Interestingly, it is reported that in families with a history of dementia, a consistently identified risk factor for AD, maternal transmission is significantly more frequent than paternal transmission.…”

Section: Disturbed Mitochondrial Genomic Homeostasis In Admentioning

confidence: 60%

Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances

Wang

Zhao

et al. 2020

Mol Neurodegeneration

786

506

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Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by impaired cognitive function due to progressive loss of neurons in the brain. Under the microscope, neuronal accumulation of abnormal tau proteins and amyloid plaques are two pathological hallmarks in affected brain regions. Although the detailed mechanism of the pathogenesis of AD is still elusive, a large body of evidence suggests that damaged mitochondria likely play fundamental roles in the pathogenesis of AD. It is believed that a healthy pool of mitochondria not only supports neuronal activity by providing enough energy supply and other related mitochondrial functions to neurons, but also guards neurons by minimizing mitochondrial related oxidative damage. In this regard, exploration of the multitude of mitochondrial mechanisms altered in the pathogenesis of AD constitutes novel promising therapeutic targets for the disease. In this review, we will summarize recent progress that underscores the essential role of mitochondria dysfunction in the pathogenesis of AD and discuss mechanisms underlying mitochondrial dysfunction with a focus on the loss of mitochondrial structural and functional integrity in AD including mitochondrial biogenesis and dynamics, axonal transport, ER-mitochondria interaction, mitophagy and mitochondrial proteostasis.

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Section: Disturbed Mitochondrial Genomic Homeostasis In Admentioning

confidence: 60%

Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances

Wang

Zhao

et al. 2020

Mol Neurodegeneration

786

506

View full text Add to dashboard Cite

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“…Inczedy-Farkas et al [22] found average FSIQ within normal limits, and lower PIQ than VIQ scores. Pronounced PIQ deficits were observed in processing speed and visuospatial functioning.…”

Section: Larger-scale Systematic Investigations Of Cognitionmentioning

confidence: 94%

Systematic review of cognitive deficits in adult mitochondrial disease

Moore

Blain

Turnbull

et al. 2019

Euro J of Neurology

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The profile and trajectory of cognitive impairment in mitochondrial disease are poorly defined. This systematic review sought to evaluate the current literature on cognition in mitochondrial disease, and to determine future research directions. A systematic review was conducted, employing PubMed, Medline, Psycinfo, Embase and Web of Science, and 360‐degree citation methods. English language papers on adult patients were included. The literature search yielded 2421 articles, of which 167 met inclusion criteria. Case reports and reviews of medical reports of patients yielded broad diagnoses of dementia, cognitive impairment and cognitive decline. In contrast, systematic investigations of cognitive functioning using detailed cognitive batteries identified focal cognitive rather than global deficits. Results were variable, but included visuospatial functioning, memory, attention, processing speed and executive functions. Conclusions from studies have been hampered by small sample sizes, variation in genotype and the breadth and depth of assessments undertaken. Comprehensive cognitive research with concurrent functional neuroimaging and physical correlates of mitochondrial disease in larger samples of well‐characterized patients may discern the aetiology and progression of cognitive deficits. These data provide insights into the pattern and trajectory of cognitive impairments, which are invaluable for clinical monitoring, health planning and clinical trial readiness.

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“…Interestingly, oxidized mtDNA activates pro-inflammatory cytokines ( Adzic et al, 2016 ) and increased inflammation is known to play a role in the development of depressive symptoms (e.g., Brymer et al, 2018 ; Wang et al, 2018 ). Variations in mtDNA have also been shown to cause cognitive impairments in mice ( Sharpley et al, 2012 ) and in humans ( Inczedy-Farkas et al, 2014 ; Petschner et al, 2018 ), and cognitive deficits are a common symptom associated with depression.…”

Section: Geneticsmentioning

confidence: 99%

Mitochondria and Mood: Mitochondrial Dysfunction as a Key Player in the Manifestation of Depression

et al. 2018

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Human and animal studies suggest an intriguing link between mitochondrial diseases and depression. Although depression has historically been linked to alterations in monoaminergic pharmacology and adult hippocampal neurogenesis, new data increasingly implicate broader forms of dampened plasticity, including plasticity within the cell. Mitochondria are the cellular powerhouse of eukaryotic cells, and they also regulate brain function through oxidative stress and apoptosis. In this paper, we make the case that mitochondrial dysfunction could play an important role in the pathophysiology of depression. Alterations in mitochondrial functions such as oxidative phosphorylation (OXPHOS) and membrane polarity, which increase oxidative stress and apoptosis, may precede the development of depressive symptoms. However, the data in relation to antidepressant drug effects are contradictory: some studies reveal they have no effect on mitochondrial function or even potentiate dysfunction, whereas other studies show more beneficial effects. Overall, the data suggest an intriguing link between mitochondrial function and depression that warrants further investigation. Mitochondria could be targeted in the development of novel antidepressant drugs, and specific forms of mitochondrial dysfunction could be identified as biomarkers to personalize treatment and aid in early diagnosis by differentiating between disorders with overlapping symptoms.

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Mitochondrial DNA Mutations and Cognition: A Case-Series Report

Cited by 33 publications

References 20 publications

Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances

Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances

Systematic review of cognitive deficits in adult mitochondrial disease

Mitochondria and Mood: Mitochondrial Dysfunction as a Key Player in the Manifestation of Depression

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