Energy Metabolism In Pd

Although the etiology of PD is unknown, the possibility of an underlying defect in mitochondrial metabolism has been addressed in several biochemical studies (76). There is evidence of reduced complex I activity in the substantia nigra in PD, and Gu et al. have suggested that a mitochondrial DNA abnormality may underlie this complex I defect in at least a subgroup of PD patients (77). Studies in other tissues, however, have produced conflicting results, perhaps in part because biochemical studies involve removal of mitochondria from their natural milieu, with consequent mechanical disruption and a loss of normal control mechanisms. In contrast, MRS provides the potential to study mitochondrial metabolism in vivo.

The rate of intracellular energy metabolism is reflected by the ratio of inorganic phosphate (Pi) to phosphocreatine (PCr), readily measured with 31P-MRS. The measurement of this ratio in resting muscle has been shown to be a useful diagnostic test for mitochondrial disease (78). Penn et al. have used 31P-MRS to investigate energy metabolism in muscle in patients with PD. The Pi/PCr ratio was significantly increased in PD, suggesting a small, generalized mitochondrial defect (79). Further studies are needed to determine whether these changes are limited to a clinically definable subset of parkinsonian individuals. 31P-MRS studies of brain have recently been reported in MSA and PD (80). In these studies, patients with MSA showed significantly increased Pi content and reduced PCr content, whereas those with PD showed significantly increased Pi but unchanged PCr, suggesting abnormal energy metabolism in both disorders.

The combination of 31P-MRS and fluorodeoxyglucose/PET has been used to suggest that temporoparietal cortical glyco-lytic and oxidative metabolism are both impaired in non-demented PD patients (81). These observations are consistent with a previous report of temporoparietal cortical reduction in NAA/Cr ratio in nondemented PD patients, which correlated with measures of global cognitive decline independently of motor impairment (73).

An alternate approach to study energy metabolism is with 1H-MRS. Normal brain energy production is derived from the oxidative metabolism of glucose by way of the Krebs cycle and, ultimately, the electron transport chain. A defect at the level of either of the two latter processes will result in decreased metabolism of pyruvate through these pathways, and increased production of lactate. Regional brain lactate concentrations can be readily assessed with 1H-MRS. For example, this methodology has been used to demonstrate increased occipital lactate levels, thereby suggesting impaired energy metabolism in Hunting-ton's disease (82). We have found similar changes in some but not all patients with PD (W. R. W. Martin, unpublished observations), providing further evidence for the presence of a mito-chondrial defect in this disorder. In contrast, however, Hoang et al. (83) have reported normal energy metabolism in the putamen and in occipital and parietal lobes when using both 31P- and 1H-MRS in patients with PD.

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