1. ¹Department of Neurology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA
2. ²Department of Neurology, and the Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri, USA
3. ³Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri, USA
4. ⁴Department of Psychiatry and the Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri, USA
5. ⁵Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA
6. ⁶Departments of Neurology, and Anatomy and Neurobiology, the Program in Physical Therapy and the Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri, USA

Correspondence: Dr WJ Powers, Department of Neurology, University of North Carolina School of Medicine, 3114 Bioinformatics Building, CB no. 7025, Chapel Hill, NC 27599-7025, USA. E-mail: powersw@neurology.unc.edu

Received 8 February 2008; Revised 13 May 2008; Accepted 29 May 2008; Published online 25 June 2008.

Abstract

Abnormal cerebral energy metabolism owing to dysfunction of mitochondrial electron transport has been implicated in the pathogenesis of Parkinson's disease (PD). However, in vivo data of mitochondrial dysfunction have been inconsistent. We directly investigated mitochondrial oxidative metabolism in vivo in 12 patients with early, never-medicated PD and 12 age-matched normal controls by combined measurements of the cerebral metabolic rate of oxygen (CMRO₂) and the cerebral metabolic rate of glucose (CMRglc) with positron emission tomography. The primary analysis showed a statistically significant 24% increase in bihemispheric CMRO₂ and no change in CMRO₂/CMRglc. These findings are inconsistent with a defect in mitochondrial oxidative phosphorylation owing to reduced activity of the mitochondrial electron transport system (ETS). Because PD symptoms were already manifest, deficient energy production owing to a reduced activity of the mitochondrial ETS cannot be a primary mechanism of neuronal death in early PD. Alternatively, this general increase in CMRO₂ could be due not to an increased metabolic demand but to an uncoupling of ATP production from oxidation in the terminal stage of oxidative phosphorylation. Whether this is the case in early PD and whether it is important in the pathogenesis of PD will require further study.