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Cognitive decline as a manifestation of mitochondrial disorders (mitochondrial dementia)

      Abstract

      Mitochondrial disorders, in particular respiratory chain diseases (RCDs), present either as single organ problem or as multi-system disease. One of the most frequently affected organs in RCDs, in addition to the skeletal muscle, is the central nervous system (CNS). CNS manifestations of RCDs include epilepsy, stroke-like episodes, migraine-like headache, ataxia, spasticity, movement disorders, psychosis, demyelination, calcification, but also dementia. Cognitive impairment may be a feature of syndromic as well as non-syndromic RCDs. Syndromic RCDs associated with cognitive impairment include MELAS, KSS, Leigh syndrome, and many others. RCDs with cognitive decline not only result from mtDNA mutations but also from mutations in nuclear genes. At onset there is often no general intellectual deterioration in these patients but specific cognitive deficits, particularly in the visual construction, attention, abstraction, or flexibility. Diagnosis of cognitive impairment from RCDs is based on neuropsychological testing, imaging studies, including MRI, PET, SPECT, or MR-spectroscopy, CSF investigations, or electroencephalography. Therapeutic strategies for dementia in RCDs rely on symptomatic measures. Only single patients may profit from cholinesterase inhibitors or memantine, antioxidants, vitamins, or other substitutes. Overall, cognitive decline in RCDs (mitochondrial dementia) needs to be included in the differentials of dementia.

      List of abbreviations:

      AD (Alzheimer's disease), ADC (Apparent diffusion coefficient map), ADEM (Acute demyelinating encephalomyelitis), ANT1 (Adenine nucleotide translocator), ATP (Adenosine-tri-phosphate), CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy), CCT (Cerebral computed tomography scan), CJD (Creutzfeld–Jacob disease), CMRI (Cerebral magnetic resonance imaging), CNS (Central nervous system), COX (Cytochrome-c oxidase), CPEO (Chronic progressive external ophthalmoplegia), CSF (Cerebrospinal fluid), DDP1 (Deafness–dystonia peptide 1), DNA (Deoxy-ribonucleic acid), DTI (Diffusion tensor imaging), DWI (Diffusion weighted imaging), EEG (Electroencephalogram), EPS (Extra-pyramidal system), FDG (Fluorodeoxyglucose), KSS (Kearns–Sayre syndrome), LHON (Leber's hereditary optic neuropathy), LH (Luteiotropic hormone), LS (Leigh syndrome), MCD (Mitochondrial disorder), MELAS (Mitochondrial encephalomyopathy, lactacidosis, stroke-like episodes), MERRF (Myoclonic epilepsy with ragged red fibers), MILS (Maternally inherited Leigh syndrome), MMS (Mini mental score), MNGIE (Mitochondrial neurogastrointestinal encephalomyopathy), MRI (Magnetic resonance imaging), MtDNA (Mitochondrial DNA), MTS (Mohr–Tranebjaerg syndrome), NARP (Neurogenic muscle weakness, ataxia, and retinitis pigmentosa), ND (Nicotine-adenosine-dehydrogenase), nDNA (Nuclear DNA), NPT (Neuropsychological testing), PDC (Pyruvate–dehydrogenase complex), PET (Positron emission tomography), P-MRS (Phosphorus-magnetic resonance spectroscopy), PNS (Peripheral nervous system), POLG (Polymerase gamma), PS (Pearson syndrome), RBD (Rapid eye movement sleep behavioral disorder), RCD (Respiratory chain disease), RNA (Ribo-nucleic acid), ROS (Reactive oxygen species), SANDO (Sensory ataxic neuropathy, dysarthria, ophthalmoplegia), SLC19A2 (Thiamin transporter protein), SLE (Stroke-like episode), SPECT (Single photon emission computed tomography), STH (Somatotropic hormone), TK2 (Tyrosine-kinase), TSH (Thyroid stimulating hormone), Twinkle (C10orf2), VEP (Visually-evoked potentials), WMS (Working Memory Scores.)

      Keywords

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