Cerebral oxygen metabolism in patients with early Parkinson's disease

Abstract 

Aim

Decreased activity of the mitochondrial electron transport chain (ETC) has been implicated in the pathogenesis of Parkinson's disease (PD). This model would most likely predict a decrease in the rate of cerebral oxygen consumption (CMRO₂). To test this hypothesis, we compared CMRO₂ and cerebral blood flow (CBF) PET scans from PD patients and healthy controls.

Materials and methods

Nine early-stage PD patients and 15 healthy age-matched controls underwent PET scans for quantitative mapping of CMRO₂ and CBF. Between-group differences were evaluated for absolute data and intensity-normalized values.

Results

No group differences were detected in regional magnitudes of CMRO₂ or CBF. Upon normalization using the reference cluster method, significant relative CMRO₂ decreases were evident in widespread prefrontal, parieto-occipital, and lateral temporal regions. Sensory-motor and subcortical regions, brainstem, and the cerebellum were spared. A similar pattern was evident in normalized CBF data, as described previously.

Conclusion

While the data did not reveal substantially altered absolute CMRO₂ in brain of PD patients, employing data-driven intensity normalization revealed widespread relative CMRO₂ decreases in cerebral cortex. The detected pattern was very similar to that reported in earlier CBF and CMRglc studies of PD, and in the CBF images from the same subjects. Thus, the present results are consistent with the occurrence of parallel declines in CMRO₂, CBF, and CMRglc in spatially contiguous cortical regions in early PD, and support the hypothesis that ETC dysfunction could be a primary pathogenic mechanism in early PD.

Keywords: Parkinson's disease, Energy metabolism, CBF, CMRO₂, Oxygen, Normalization, Positron emission tomography