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Abstract The effective dose represents the overall internal radiation exposure to the whole body when exposed to radiation sources. This study aims to compare conventional and software-aided methods to derive the effective dose. In the present study, 8F-T807 and 18F-Mefway, specific radiotracers for the paired helical tau and serotonin 1A receptor, were administered to healthy subjects (n = 6, each radiotracer), following which whole-body positron emission tomography (PET) images were obtained for 2 h. Subsequently, time-activity curves for major organs were obtained, and the residence times were calculated using the “conventional” and “Residence Times model” tools in PMOD software. The residence times from each method was input into OLINDA/EXM software, and the effective dose was estimated. The differences in the average residence times of the brain, heart, lung, and liver were 18.4, 20.8, 10.4, and 13.3% for 18F-T807, and 17.5, 16.4, 18.1, and 17.5% for 18F-Mefway, respectively. For the mean effective dose, the error rates between the methods were 3.8 and 1.9% for 18F-T807 and 18F-Mefway, respectively. The organs that showed the greatest difference in the absorbed dose were the urinary bladder for 18F-T807 (40.4%) and the liver for 18F-Mefway (14.1%). This method of obtaining the residence time using PMOD can be easily used to derive the effective dose, and is applicable in evaluating the safety of radiotracers for clinical trials.

Abstract Epidemiological studies have reported a link between essential tremor (ET) and Parkinson’s disease (PD). Recent studies have suggested ET as a possible neurodegenerative disease whose subgroup contained Lewy bodies in the brainstem, as in PD. PD with antedated ET (PDconv) might exhibit traits different from those of the pure form of ET or PD. This study aimed to unveil the interplay between PD and premorbid ET, which might be the core pathobiology that differentiates PDconv from PD. The study included 51 ET, 32 PDconv, and 95 PD patients who underwent positron emission tomography using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and 123I-meta-iodobenzylguanidine myocardial scintigraphy to analyze central dopaminergic and peripheral noradrenergic integrity. The results show that PDconv group followed the typical striatal pathology of PD but with a delay in noradrenergic impairment as it caught up with the denervating status of PD a few years after PD diagnosis. Whereas the two PD subtypes displayed similar patterns of presynaptic dopamine transporter deficits, ET patients maintained high densities in all subregions except thalamus. Presynaptic dopaminergic availability decreased in a linear or quadratic fashion across the three groups (ET vs. PDconv vs. PD). The age at onset and duration of ET did not differ between pure ET and PDconv patients and did not influence the striatal monoamine status. The myocardium in PDconv patients was initially less denervated than in PD patients, but it degenerated more rapidly. These findings suggest that PDconv could be a distinctive subclass in which the pathobiology of PD interacts with that of ET in the early phase of the disease.

Abstract Decreased cancer risk has been reported in patients with Parkinson’s disease (PD), and cancer prior to PD can have a protective effect on PD risk. We investigated cancer history prior to PD diagnosis to determine if such history can enhance motor reserve in PD by assessing the association between motor deficits and striatal subregional dopamine depletion. A total of 428 newly diagnosed, drug-naïve PD patients was included in the study. PD patients were categorized into three groups of no prior neoplasia, premorbid precancerous condition, and premorbid malignant cancer before PD diagnosis. Parkinsonian motor status was assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score and modified Hoehn and Yahr stage score. All patients underwent positron emission tomography (PET) with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (18F-FP-CIT), and the regional standardized uptake value ratios (SUVRs) were analyzed with a volume-of-interest template among the groups. The UPDRS motor score negatively correlated with SUVRs in the posterior putamen for all patient groups. Groups with neoplasia, especially those with premorbid cancer, showed lower motor scores despite similar levels of dopamine depletion in the posterior putamen relative to those without neoplasia. These results suggest that premorbid cancer acts as a surrogate for motor reserve in patients with PD and provide imaging evidence that history of cancer has a protective effect on PD.

Abstract Drug-induced parkinsonism (DIP) is caused by a dopamine receptor blockade and is a major cause of misleading diagnosis of Parkinson’s disease (PD). Striatal dopamine activity has been investigated widely in DIP; however, most studies with dopamine transporter imaging have focused on the clinical characteristics and prognosis. This study investigated differences in striatal subregional monoamine availability among patients with DIP, normal controls, and patients with early PD. Thirty-five DIP patients, the same number of age-matched PD patients, and 46 healthy controls were selected for this study. Parkinsonian motor status was examined. Brain magnetic resonance imaging and positron emission tomography with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane were performed, and the regional standardized uptake values were analyzed with a volume-of-interest template and compared among the groups. The groups were evenly matched for age, but there were numerically more females in the DIP group. Parkinsonian motor symptoms were similar in the DIP and PD groups. Monoamine availability in the thalamus of the DIP group was lower than that of the normal controls and similar to that of the PD group. In other subregions (putamen, globus pallidus, and ventral striatum), monoamine availability in the DIP group and normal controls did not differ and was higher than that in the PD group. This difference compared to healthy subject suggests that low monoamine availability in the thalamus could be an imaging biomarker of DIP.

Abstract To estimate dopaminergic dysfunction in patients with Parkinson disease (PD) during the premotor stage and to investigate the effect of genetic factors on the trajectories. Using longitudinal dopamine transporter single-photon emission computed tomography data from 367 sporadic PD (sPD), 72 LRRK2 (G2019S), and 39 GBA (N370S) PD patients in the Parkinson’s Progression Markers Initiative (PPMI) study, we estimated the temporal trajectories of putaminal-specific binding ratios using an integrating function between baseline values and their annual change rates. In order to test reproducibility, we computed another trajectory for sPD using positron emission tomography data of 38 sPD patients at Gangnam Severance Hospital (GSH). Temporal trajectories of sPD were compared between the groups separated by age at onset (AAO) and polygenic load for common PD risk variants, and also compared with genetic PD. sPD patients in both the PPMI and GSH cohorts showed similar onset of dopaminergic degeneration around 10 years before motor onset. Early-onset PD patients exhibited later onset of degeneration and a faster decline in dopaminergic activity during the premotor period than late-onset patients. sPD patients with high polygenic load were associated with earlier onset and slower progression of dopaminergic dysfunction. Compared to the sPD and LRRK2 PD groups, GBA PD patients exhibited faster deterioration of dopaminergic function during the premotor stage. Dopaminergic dysfunction in PD appears to start about 10 years before motor onset. Genetic factors may be contributing to the heterogeneity of dopaminergic deterioration during the premotor stage.

Abstract Full dynamics of biofluid biomarkers have been unknown in patients with Parkinson’s disease (PD). Using data from 396 PD patients and 182 controls in the Parkinson's Progression Markers Initiative (PPMI) database, we estimated long-term temporal trajectories of CSF α-synuclein (α-syn), amyloid-β (Aβ), total tau (t-tau), phosphorylated tau (p-tau) and serum neurofilament light chain (NfL) by integrating function between the baseline levels and annual changes. At baseline, PD patients showed lower CSF α-syn, Aβ, t-tau and p-tau levels than those of the controls. In all PD patients, CSF α-syn and Aβ decreased in a negative exponential pattern before the onset of motor symptoms, whereas CSF t-tau and p-tau, and serum NfL increased. Patients with cognitive impairment exhibited faster decline of Aβ and α-syn and faster rise of t-tau, p-tau and NfL, when compared to those without. Similarly, low Aβ group showed earlier decline of α-syn, faster rise of t-tau, p-tau and NfL, and faster decline of cognitive performances, when compared to high Aβ group. Our results suggest that longitudinal changes in biomarkers can be influenced by cognitive impairment and Aβ burden at baseline. PD patients with Aβ pathology may be associated with early appearance of α-synuclein pathology, rapid progression of axonal degeneration and neurodegeneration, and consequently greater cognitive decline.

Abstract This study aimed to evaluate the effect of levodopa on the phase coordination index (PCI) and gait asymmetry (GA) of patients with Parkinson’s disease (PD) and to investigate correlations between the severity of motor symptoms and gait parameters measured using an inertial sensor. Twenty-six patients with mild-to-moderate-stage PD who were taking levodopa participated in this study. The Unified Parkinson’s Disease Rating Scale part III (UPDRS III) was used to assess the severity of motor impairment. The Postural Instability and Gait Difficulty (PIGD) subscore was calculated from UPDRS III. Patients were assessed while walking a 20-m corridor in both “OFF” and “ON” levodopa medication states, and gait analysis was performed using inertial sensors. We investigated the changes in gait parameters after taking levodopa and the correlations between UPDRS III, PIGD, and gait parameters. There was a significant improvement in PCI after taking levodopa. No significant effect of levodopa on GA was found. In “OFF” state, PCI and GA were not correlated with UPDRS III and PIGD. However, in “ON” state, PCI was the only gait parameter correlating with UPDRS III, and it was also highly correlated with PIGD compared to other gait parameters. Significant improvement in bilateral-phase coordination was identified in patients with PD after taking levodopa, without significant change in gait symmetricity. Considering the high correlation with UDPRS III and PIGD in “ON” states, PCI may be a useful and quantitative parameter to measure the severity of motor symptoms in PD patients who are on medication.