How important could this paper turn out to be?!! It addresses one of the key questions regarding DAT-SPECT imaging and PD - does DAT deficit indicate neuronal loss or dysfunction?? This is important because once cells have gone, they are not coming back, but with dysfunction comes the hope of being able to restore function.
The numbers are small I know, but this provides further support that the DAT-SPECT could be a good biomarker of prodromal PD... perhaps not just by showing a slowing of decline over time, but potentially even an improvement in appearances given the right neuro-protective agent...
Neurology. 2017 Mar 10. pii: 10.1212/WNL.0000000000003810. doi: 10.1212/WNL.0000000000003810. [Epub ahead of print]
Saari L, Kivinen K, Gardberg M, Joutsa J, Noponen T, Kaasinen V.
http://www.neurology.org/content/early/2017/03/10/WNL.0000000000003810.long
OBJECTIVE:
To examine possible associations between in vivo brain dopamine transporter SPECT imaging and substantia nigra pars compacta (SNc) neuronal survival in Parkinson disease (PD).
METHODS:
Nigral neuron numbers were calculated for 18 patients (11 patients with neuropathologically confirmed PD) who had been examined with dopamine transporter (DAT) SPECT before death. Correlation analyses between SNc tyrosine hydroxylase (TH)-positive and neuromelanin-containing neuron counts and DAT striatal specific binding ratios (SBRs) were performed with semiquantitative region of interest-based and voxel-based analyses.
RESULTS:
Mean putamen SBR did not correlate with the number of substantia nigra TH-positive (r = -0.11, p = 0.66) or neuromelanin-containing (r = -0.07, p = 0.78) neurons. Correlations remained clearly nonsignificant when the time interval between SPECT and death was used as a covariate, when the voxel-based analysis was used, and when only patients with PD were included.
CONCLUSIONS:
This cohort study demonstrates that postmortem SNc neuron counts are not associated with striatal DAT binding in PD. These results fit with the theory that there is no correlation between the number of substantia nigra neurons and striatal dopamine after a certain level of damage has occurred. Striatal DAT binding in PD may reflect axonal dysfunction or DAT expression rather than the number of viable neurons.
Experience of return of sense of smell some years after its loss in PD seems to indicate that dopaminergic neurons only become dysfunctional but remain viable and capable of recovery when the cause of the dysfunction is removed or reduced. Concentration on death of cells in the substantia nigra is likely to be unproductive at such a late stage.
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