Idiopathic
Parkinson’s disease (PD) is the most frequent cause of clinical parkinsonism.
However, the diagnostic accuracy of PD is suboptimal. One biomarker that
assists with the parkinsonism differential diagnostics is functional dopamine
transporter (DAT) imaging. The accuracy of DAT single photon emission computed
tomography (SPECT) imaging is high for detecting striatal dopamine deficiency
associated with neurodegenerative parkinsonism. However, its limitations and
associations with clinical characteristics are not yet fully understood,
particularly in patients with clinical parkinsonism of uncertain origin.

In this thesis, the retrospective studies investigated
the associations between striatal dopamine deficiency and structural midbrain
atrophy measurements and long-term survival in PD patients. As both visual and
semi-quantitative analysis methods are broadly used for DAT SPECT scans, the
concordance between these methods was investigated. The cross-sectional
clinical and imaging study investigated which of the parkinsonian motor signs
are associated with a higher likelihood of striatal DAT deficiency, and whether
these signs are associated with DAT loss in certain striatal regions in
patients with neurodegenerative parkinsonism.

The results showed that there were no associations
between the midbrain-to-pons ratios, suggestive of midbrain atrophy, and
striatal dopamine deficiency in DP. Expert visual DAT image analyses and the
semi-quantitative analyses did not match in 10% of cases; however, none of
these patients had neurodegenerative parkinsonism according to the clinical
follow-ups. The level of DAT deficiency was not associated with survival in PD.
Finally, both upper extremity rigidity and hypomimia were independently
associated with a higher likelihood of striatal dopamine deficiency. Hypomimia
was specifically associated with caudate nucleus dopamine loss in patients with
abnormal striatal DAT binding.

The results indicate that midbrain-to-pons ratios
cannot be used to estimate the level of striatal DAT deficiency in patients
with PD. The scans that showed a discrepancy between the different analysis
methods should likely be interpreted as normal. Dopamine deficiency levels
cannot be used to predict patient survival in PD. Presence of upper extremity
rigidity and hypomimia in clinical neurological examinations may be useful
markers in the differential diagnosis of clinically uncertain parkinsonism and
tremor as they point to striatal DAT deficiency.