Perfusion and Metabolism PET studies in Parkinson's Disease
Accepted by: Faculty of Health Sciences Aarhus
March 27, 2008
Official opponents: Klaus Leenders, Groningen, The Netherlands
, Peter Johannsen, Copenhagen, Denmark
, Poul Videbech, Aarhus, Denmark
Tutors: Albert Gjedde, Aarhus, Denmark
, Paul Cumming, Aarhus, Denmark
, Karen ěstergaard, Aarhus, Denmark
Published in the PhD Database:
February 19, 2009
Perfusion and Metabolism PET Studies in Parkinson┐s Disease
The dissertation is based upon three PET studies of cerebral blood flow (CBF) and oxygen consumption in the brain of patients with Parkinson┐s disease (PD) and control subjects.
The NMDA receptor antagonist memantine is used for treating patients with Alzheimer┐s disease and studies of animal models have shown a possible neuroprotective effect of this drug in both PD and Alzheimer┐s disease. We investigated the effect of six weeks of memantine treatment on ten patients with early PD. Contrary to our hypotheses, we did not see an effect of memantine on the oxygen consumption in the basal ganglia in PD, but a tendency towards generally reduced CBF. Memantine may affect the basal neurovascular coupling mechanisms.
In earlier studies of PD, a characteristic pattern of altered perfusion and metabolism seems able to differentiate PD from other brain disorders. The pattern has also been claimed to be informative about the underlying neurometabolic disturbances in PD. This PD-related pattern consists of relatively increased metabolism in the putamen, pallidum, cerebellum, and primary motor cortex with concomitant hypometabolism in frontal and parietal cortical areas. However, this pattern is not in agreement with findings in animal models of PD, and moreover, similar patterns have been reported in Schizophrenia, Alzheimer┐s disease, hepatic encephalopathy, and healthy aging.
In study II we demonstrated that this PD pattern can arise as a consequence of a methodological bias. To reduce data variance in PET data certain normalization routines are commonly used, i.e. to divide the value in each region or voxel by the global mean value. By comparing healthy aged and young volunteers, and by comparing aged subjects to patients with hepatic encephalopathy we demonstrated a pattern, which is highly similar to the PD pattern. Thus the pattern cannot be completely specific for PD. The white matter values exhibited no between-group differences in any of the comparisons. White matter is therefore a more suitable normalization reference region compared to the global mean. In study III, we performed a meta-analysis of all available quantitative PET studies of PD and found that the brain global mean CBF and glucose consumption is most likely decreased in PD, which invalidates normalization to the global mean. White matter was unchanged, thus qualifying white matter as a superior reference region in PD also. Upon normalizing to white matter, we demonstrated that PD patients display more pronounced decreases in cortical perfusion and metabolism, even at early disease stages.