title: Dementia in Parkinson's disease is associated with enhanced mitochondrial complex I deficiency.
abstract: BACKGROUND
  Dementia is a common feature of Parkinson's disease (PD), but the neuropathological changes associated with the development of Parkinson's disease dementia (PDD) are only partially understood. Mitochondrial dysfunction is a hallmark of PD but has not been studied in PDD.
  
  
  METHODS
  Molecular and biochemical approaches were used to study mitochondrial activity and quantity in postmortem prefrontal cortex tissue. Tissues from pathologically confirmed PD and PDD patients and from age-matched controls were used to analyze the activity of mitochondrial enzyme complex nicotinamide adenine dinucleotide:ubiquinone oxidoreductase, or complex I (the first enzyme in the mitochondrial respiratory chain), mitochondrial DNA levels, and the expression of mitochondrial proteins.
  
  
  RESULTS
  Complex I activity was significantly decreased (27% reduction; analysis of variance with Tukey's post hoc test; P < 0.05) in PDD patients, and mitochondrial DNA levels were also significantly decreased (18% reduction; Kruskal-Wallis analysis of variance with Dunn's multiple comparison test; P < 0.05) in PDD patients compared with controls, but neither was significantly reduced in PD patients. Overall, mitochondrial biogenesis was unaffected in PD or PDD, because the expression of mitochondrial proteins in patients was similar to that in controls.
  
  
  CONCLUSIONS
  Patients with PDD have a deficiency in mitochondrial complex I activity and reduced mitochondrial DNA levels in the prefrontal cortex without a change in mitochondrial protein quantity. Therefore, mitochondrial complex I deficiency and reduced mitochondrial DNA in the prefrontal cortex may be a hallmark of dementia in patients with PD.
authors: Wolfson Center for Age-Related Diseases, King's College London, Guy's Campus, London, United Kingdom.
authors: Ariana P
authors: AP
authors: Gatt
authors: Wolfson Center for Age-Related Diseases, King's College London, Guy's Campus, London, United Kingdom.
authors: Olivia F
authors: OF
authors: Duncan
authors: Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
authors: Johannes
authors: J
authors: Attems
authors: Wolfson Center for Age-Related Diseases, King's College London, Guy's Campus, London, United Kingdom.
authors: Paul T
authors: PT
authors: Francis
authors: Wolfson Center for Age-Related Diseases, King's College London, Guy's Campus, London, United Kingdom.
authors: Clive G
authors: CG
authors: Ballard
authors: Wolfson Center for Age-Related Diseases, King's College London, Guy's Campus, London, United Kingdom.
authors: Joseph M
authors: JM
authors: Bateman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003704:Dementia / Q000150:complications / Q000378:metabolism; D042967:Electron Transport Complex I / Q000172:deficiency* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000150:complications / Q000209:etiology* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010300:Parkinson Disease / Q000150:complications / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D042967:Electron Transport Complex I
keywords: Parkinson's; complex I; dementia; mitochondria; mitochondrial DNA