Magnetic resonance imaging assessment of substantia nigral iron deposition in Parkinson's disease: a meta-analysis.

OBJECTIVE: The pathogenesis of Parkinson's disease (PD) is associated with abnormal iron accumulation. Magnetic resonance imaging (MRI) studies have shown that patients with Parkinson's disease have an increased amount of iron in their substantia nigra (SN). We have undertaken a meta-analysis of studies using MRI in PD, to explore the potential role of MRI in diagnosing PD using abnormal iron deposition in SN as a candidate biomarker. MATERIALS AND METHODS: Searches of PubMed, Embase, and Medline databases revealed 16 studies that compared PD patients and healthy controls (HC). A sensitivity analysis and subgroup analysis were performed to evaluate the reliability of our results. Estimates were pooled by the fixed-effects model. As an expression of I2, we computed the proportion of variation due to heterogeneity. RESULTS: We included 16 studies with sample sizes of 435 PD and 355 HC in our meta-analysis. Results showed that SN iron deposition was significantly elevated (p<0.00001) in patients with PD compared to HC ones (SMD=0.72, 95% confidence interval 0.57 to 0.87, p<0.00001). CONCLUSIONS: Our findings, based on a homogeneous group-level analysis, suggest that MRI-based SN iron deposition could be used to distinguish PD from HC. For a more rigorous investigation of SN iron deposition in PD, larger cohort studies are needed.

Dopamine and serotonin in human substantia nigra track social context and value signals during economic exchange.

Dopamine and serotonin are hypothesized to guide social behaviours. In humans, however, we have not yet been able to study neuromodulator dynamics as social interaction unfolds. Here, we obtained subsecond estimates of dopamine and serotonin from human substantia nigra pars reticulata during the ultimatum game. Participants, who were patients with Parkinson's disease undergoing awake brain surgery, had to accept or reject monetary offers of varying fairness from human and computer players. They rejected more offers in the human than the computer condition, an effect of social context associated with higher overall levels of dopamine but not serotonin. Regardless of the social context, relative changes in dopamine tracked trial-by-trial changes in offer value-akin to reward prediction errors-whereas serotonin tracked the current offer value. These results show that dopamine and serotonin fluctuations in one of the basal ganglia's main output structures reflect distinct social context and value signals.

Assessment of tRNAThr and tRNAGln Variants and Mitochondrial Functionality in Parkinson's Disease (PD) Patients of Tamil Nadu Population.

Parkinson's disease (PD) is speculated with genetic and environmental factors. At molecular level, the mitochondrial impact is stated to be one of the causative reasons for PD. In this study, we investigated the mitochondrial membrane potential (MMP), reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels along with mitochondrial tRNA alterations among three age categories of PD. By determining the genetic and organellar functionality using molecular techniques, the ROS levels were reported to be high with decreased MMP and ATP in the late-onset age group than in other two age categories. Likewise, the tRNA significancy in tRNAThr and tRNAGln was noticed with C4335T and G15927A mutations in late-onset and early-onset PD groups respectively. Therefore, from the findings, ageing has shown a disruption in tRNA metabolism leading to critical functioning of ATP synthesis and MMP, causing oxidative stress in PD patients. These physiological outcomes show that ageing has a keen role in the divergence of mitochondrial function, thereby proving a correlation with ageing and maintenance of mitochondrial homeostasis in PD.

Quantitative dopamine transporter imaging assessment in Parkinson's disease patients carrying GBA gene mutations compared with idiopathic PD patients: A case-control study.

BACKGROUND: Genetic risk factors impact around 15% of Parkinson's disease (PD) patients and at least 23 variants have been identified including Glucocerebrosidase (GBA) gene variants. Using different clinical and instrumental qualitative-based data, various studies have been published on GBA-PD cohorts which suggested possible differences in dopaminergic nigrostriatal denervation pattern, particularly in caudate and putamen nuclei. METHODS: This retrospective study included two consecutive homogenous cohorts of GBA-PD and idiopathic (I-PD) patients. Each consecutive GBA-PD patient has been matched with a 1:1 pairing method with a consecutive I-PD subject according to age, age at disease onset, sex, Hoehn & Yahr (H&Y) staging scale and comorbidity level (CCI). Semiquantitative volumetric data by the DaTQUANTTM software integrated in the DaTSCAN exam performed at time of the diagnosis (SPECT imaging performed according to current guidelines of I-123 FPCIT SPECT imaging) were extrapolated. Bilateral specific binding ratios (SBR) at putamen and caudate levels were calculated, using the occipital lobes uptake. The Mann-Whitney test was performed to compare the two cohorts while the Spearman's test was used to find correlations between motor and volumetric data in each group. Bonferroni correction was used to account for multiple comparisons. RESULTS: Two cohorts of 25 patients each (GBA-PD and I-PD), were included. By comparing GBA-PD and I-PD patients, lower SBR values were found in the most affected anterior putamen and left caudate of the GBA-PD cohort. Furthermore, in the GBA-PD cohort the SBR of the most affected posterior putamen negatively correlated with the H&Y scale. However, none of these differences or correlations remained significant after Bonferroni correction for multiple comparisons. CONCLUSIONS: We observed differences in SBR values in GBA-PD patients compared with I-PD. However, these differences were no longer significant after Bonferroni multiple comparisons correction highlighting the need for larger, longitudinal studies.

Influence of brain atrophy using semiquantitative analysis in [123I]FP-CIT single-photon emission computed tomography by a Monte Carlo simulation study.

The specific binding ratio (SBR) is an objective indicator of N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-[123I] iodophenyl) nortropane ([123I]FP-CIT) single-photon emission computed tomography (SPECT) that could be used for the diagnosis of Parkinson's disease and Lewy body dementia. One of the issues of the SBR analysis is that the setting position of the volume of interest (VOI) may contain cerebral ventricles and cerebral grooves. These areas may become prominent during the brain atrophy analysis; however, this phenomenon has not been evaluated enough. This study thus used Monte Carlo simulations to examine the effect of brain atrophy on the SBR analysis. The brain atrophy model (BAM) used to simulate the three stages of brain atrophy was made using a morphological operation. Brain atrophy levels were defined in the descending order from 1 to 3, with Level 3 indicating to the most severe damage. Projection data were created based on BAM, and the SPECT reconstruction was performed. The ratio of the striatal to background region accumulation was set to a rate of 8:1, 6:1, and 4:1. The striatal and the reference VOI mean value were decreased as brain atrophy progressed. Additionally, the Bolt's analysis methods revealed that the reference VOI value was more affected by brain atrophy than the striatal VOI value. Finally, the calculated SBR value was overestimated as brain atrophy progressed, and a similar trend was observed when the ratios of the striatal to background region accumulation were changed. This study thus suggests that the SBR can be overestimated in cases of advanced brain atrophy.

Energy expenditure, body composition and dietary habits in progressive supranuclear palsy.

INTRODUCTION: Little is known about metabolic changes in progressive supranuclear palsy. Goals of the present study are to: (1) investigate whether early progressive supranuclear palsy is associated with changes in energy expenditure, body composition and dietary intake compared with Parkinson's disease and healthy controls; (2) assess the accuracy of the Harris-Benedict equation to predict measured rest energy expenditure in progressive supranuclear palsy; (3) verify differences according to sex, phenotypes, disease severity and presence of dysphagia in progressive supranuclear palsy. METHODS: Twenty-one progressive supranuclear palsy, 41 Parkinson's disease and nine healthy controls were included. Rest energy expenditure was assessed with indirect calorimeter, body composition with bio-impedance analysis and physical activity and dietary intake were estimated with a validated frequency questionnaire. Parametric testing was used to analyze differences between groups. RESULTS: Progressive supranuclear palsy showed reduced total daily energy expenditure and physical activity compared to both other cohorts (p < 0.001) and a tendency toward lower fat-free mass compared to Parkinson's disease (p > 0.05). Limited accuracy was shown for the Harris-Benedict equation (accurate prediction frequency < 60%). Greater disease severity was associated with lower rest energy expenditure (p = 0.030), fat-free mass (p = 0.026) and muscle mass (p = 0.029). CONCLUSION: Greater disease severity is associated with reduction in rest energy expenditure likely due to the reduction in lean mass and muscle mass. Such data may pave the way to clinical trials evaluating the efficacy of muscle-targeted nutritional support and physical therapy in preserving muscle mass and improving motor performances in progressive supranuclear palsy at early stages.

Differential dopaminergic modulation of spontaneous cortico-subthalamic activity in Parkinson's disease.

Pathological oscillations including elevated beta activity in the subthalamic nucleus (STN) and between STN and cortical areas are a hallmark of neural activity in Parkinson's disease (PD). Oscillations also play an important role in normal physiological processes and serve distinct functional roles at different points in time. We characterised the effect of dopaminergic medication on oscillatory whole-brain networks in PD in a time-resolved manner by employing a hidden Markov model on combined STN local field potentials and magnetoencephalography (MEG) recordings from 17 PD patients. Dopaminergic medication led to coherence within the medial and orbitofrontal cortex in the delta/theta frequency range. This is in line with known side effects of dopamine treatment such as deteriorated executive functions in PD. In addition, dopamine caused the beta band activity to switch from an STN-mediated motor network to a frontoparietal-mediated one. In contrast, dopamine did not modify local STN-STN coherence in PD. STN-STN synchrony emerged both on and off medication. By providing electrophysiological evidence for the differential effects of dopaminergic medication on the discovered networks, our findings open further avenues for electrical and pharmacological interventions in PD.

Assessment of Cytotoxicity of α-Synuclein in Budding Yeast Using a Spot Growth Assay and Fluorescent Microscopy.

The budding yeast Saccharomyces cerevisiae is a model organism amenable both to genetic analysis and cell biology. Due to these advantages, yeast has provided platforms to examine the properties of pathogenic proteins involved in human diseases. The methods used to examine the cytotoxicity and intracellular localization of α-Synuclein, a human neuronal protein implicated in Parkinson's disease, using yeast have been described herein. These methods are readily accessible to researchers or graduate students unfamiliar with experiments using yeast and applicable to larger scale analyses, such as high-throughput genetic and chemical screenings.

The Functional Assessment of LRRK2 in Caenorhabditis elegans Mechanosensory Neurons.

The nematode Caenorhabditis elegans (C. elegans) is a powerful model organism to systematically analyze the functions of genes of interest in vivo. Especially, C. elegans nervous system is suitable for morphological and functional analyses of neuronal genes due to its optical transparency of the body and the well-established anatomy including neural connections. The C. elegans ortholog of Parkinson's disease-associated gene LRRK2, named lrk-1, has been shown to play a role in the regulation of axonal morphology in a subset of neurons. Here I describe the detailed methodologies for the assessment of LRK-1/LRRK2 function as well as the analysis of genetic interaction involving lrk-1/LRRK2 by performing live imaging of C. elegans mechanosenrory neurons.

Parkinson's disease in women: Mechanisms underlying sex differences.

Parkinson's disease is a neurodegenerative disease which is associated with different motor, cognitive and mood-related problems. Though it has been established that Parkinson's disease is less prevalent in women in comparison to men, the differences tend to diminish with the advancing age. Different genetic, hormonal, neuroendocrinal and molecular players contribute towards the differences in the Parkinson's disease pathogenesis. Furthermore, data available with respect to the therapeutic management of Parkinson's disease in females is limited; women often tend to suffer more from the side effects of the currently available drugs. The present review highlights the sex-specific differences which play a role in the manifestation of these symptoms and side effects of the currently available therapeutic strategies. We have also discussed the current and upcoming therapeutic strategies which are in the clinical trials such as adenosine 2A (A2A) receptor antagonists, estrogen replacement therapy, α-synuclein targeting vaccines and antibodies, Botulinum toxin A, Fas-associated factor-1 (FAF-1) inhibitors, thiazolidinediones, 5-HT1A receptor agonists, dopamine D1/D5 receptor agonists, Glucagon-like peptide 1 (GLP-1) analogues and certain plant based principles for the treatment of Parkinson's disease in women.

Inhibition of Orexin/Hypocretin Neurons Ameliorates Elevated Physical Activity and Energy Expenditure in the A53T Mouse Model of Parkinson's Disease.

Aside from the classical motor symptoms, Parkinson's disease also has various non-classical symptoms. Interestingly, orexin neurons, involved in the regulation of exploratory locomotion, spontaneous physical activity, and energy expenditure, are affected in Parkinson's. In this study, we hypothesized that Parkinson's-disease-associated pathology affects orexin neurons and therefore impairs functions they regulate. To test this, we used a transgenic animal model of Parkinson's, the A53T mouse. We measured body composition, exploratory locomotion, spontaneous physical activity, and energy expenditure. Further, we assessed alpha-synuclein accumulation, inflammation, and astrogliosis. Finally, we hypothesized that chemogenetic inhibition of orexin neurons would ameliorate observed impairments in the A53T mice. We showed that aging in A53T mice was accompanied by reductions in fat mass and increases in exploratory locomotion, spontaneous physical activity, and energy expenditure. We detected the presence of alpha-synuclein accumulations in orexin neurons, increased astrogliosis, and microglial activation. Moreover, loss of inhibitory pre-synaptic terminals and a reduced number of orexin cells were observed in A53T mice. As hypothesized, this chemogenetic intervention mitigated the behavioral disturbances induced by Parkinson's disease pathology. This study implicates the involvement of orexin in early Parkinson's-disease-associated impairment of hypothalamic-regulated physiological functions and highlights the importance of orexin neurons in Parkinson's disease symptomology.

Assessment of the role of non-coding RNAs in the pathophysiology of Parkinson's disease.

Parkinson's disease (PD) is the second main neurodegenerative disease causing motor abnormalities in the middle-aged and old individuals. In some cases, cognitive dysfunction also occurs. The clinical signs of PD are bradykinesia, rigidity and resting tremor. As these signs might be detected in other neurological conditions such as multiple systems atrophy and corticobasal degeneration, it is necessary to find specific and sensitive markers for this disorder. Non-coding RNAs are implicated in the different PD-associated features such as α-synuclein expression and Lewy body construction, mitochondrial dysfunction, apoptosis, neuroinflammation and defects in glial cell-derived neurotrophic factor. Several researches have confirmed dysregulation of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in brain tissues, plasma exosomes and leukocytes of affected individuals or animal models of PD. A number of these transcripts directly regulate the neurodegenerative process in PD. In the current study, we review the current data about dysregulation of ncRNAs and the role of their genomic variants in the pathogenesis of PD.

Expanded access: opening doors to personalized medicine for rare disease patients and patients with neurodegenerative diseases.

In neurodegenerative diseases, a select set of neuron population displays early vulnerability and undergoes progressive degeneration. The heterogeneity of the cerebral cortex and the heterogeneity of patient populations diagnosed with the same disease offer many challenges for developing effective and long-term treatment options. Currently, patients who are considered to have a 'rare' disease are left with no hopes for cure, and many of the neurodegenerative diseases progress fast without any effective solutions. However, as our understanding of disease mechanisms evolve, we begin to realize that the boundaries between diseases are not as sharp as once believed. There are many patients who develop disease due to common underlying causes and mechanisms. As we move forward with drug discovery effort, it becomes obvious that we will have to shift our focus from finding a cure for a disease, to finding solutions to the disease-causing cellular mechanisms so that patients can be treated by mechanism-based strategies. This paradigm shift will lay the foundation for personalized medicine approaches for neurodegenerative disease patients and patients diagnosed with a rare disease.

Chitosan coated synergistically engineered nanoemulsion of Ropinirole and nigella oil in the management of Parkinson's disease: Formulation perspective and In vitro and In vivo assessment.

The research presented aims at developing Ropinirole hydrochloride (RHCl) nanoemulsion (NE) with nigella oil for Parkinson's disease (PD). In silico study was done to explore interactions of ropinirole and thymoquinone at receptor site (TNF-α and NFK-ß). Ropinirole and Thymoquinone forms a hydrogen bond with residue Arginine 201 and residue Arginine 253 with a bond length of 1.89 Å and 2.30 Å at the NF-κß receptor. NE was optimized using Central Composite Rotatable Design (CCRD). The globule size of chitosan coated NE, Polydispersity index (PDI) and zeta potential were 183.7 ± 5.2 nm, 0.263 ± 0.005, and 24.9 mV respectively. NE exhibited 85.28% transmittance showing the formulation was clear and transparent. TEM showed that NE had spherical globules with no aggregation. The formulation had a stable pH value of 5.8 ± 0.18. In vitro release and permeation studies exhibited 2 folds and 3.4 folds enhancement when compared with the drug suspension. Neurobehavioral activity and biochemical parameters corroborated well with the pharmacokinetic results. Histopathological study and immunohistochemical analysis were performed to get better picture of 6-OHDA induced toxicity and reversal of PD symptoms. Thus, the NE tailored is a promising synergistic approach yielding enticing outcomes for better management of PD related symptoms.

Assessment of 18F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy.

Importance: Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers that support diagnosis. Objective: To investigate the potential of the novel tau radiotracer 18F-PI-2620 as a biomarker in patients with clinically diagnosed PSP. Design, Setting, and Participants: In this cross-sectional study, participants underwent dynamic 18F-PI-2620 positron emission tomography (PET) from 0 to 60 minutes after injection at 5 different centers (3 in Germany, 1 in the US, and 1 in Australia). Patients with PSP (including those with Richardson syndrome [RS]) according to Movement Disorder Society PSP criteria were examined together with healthy controls and controls with disease. Four additionally referred individuals with PSP-RS and 2 with PSP-non-RS were excluded from final data analysis owing to incomplete dynamic PET scans. Data were collected from December 2016 to October 2019 and were analyzed from December 2018 to December 2019. Main Outcomes and Measures: Postmortem autoradiography was performed in independent PSP-RS and healthy control samples. By in vivo PET imaging, 18F-PI-2620 distribution volume ratios were obtained in globus pallidus internus and externus, putamen, subthalamic nucleus, substantia nigra, dorsal midbrain, dentate nucleus, dorsolateral, and medial prefrontal cortex. PET data were compared between patients with PSP and control groups and were corrected for center, age, and sex. Results: Of 60 patients with PSP, 40 (66.7%) had RS (22 men [55.0%]; mean [SD] age, 71 [6] years; mean [SD] PSP rating scale score, 38 [15]; score range, 13-71) and 20 (33.3%) had PSP-non-RS (11 men [55.0%]; mean [SD] age, 71 [9] years; mean [SD] PSP rating scale score, 24 [11]; score range, 11-41). Ten healthy controls (2 men; mean [SD] age, 67 [7] years) and 20 controls with disease (of 10 [50.0%] with Parkinson disease and multiple system atrophy, 7 were men; mean [SD] age, 61 [8] years; of 10 [50.0%] with Alzheimer disease, 5 were men; mean [SD] age, 69 [10] years). Postmortem autoradiography showed blockable 18F-PI-2620 binding in patients with PSP and no binding in healthy controls. The in vivo findings from the first large-scale observational study in PSP with 18F-PI-2620 indicated significant elevation of tracer binding in PSP target regions with strongest differences in PSP vs control groups in the globus pallidus internus (mean [SD] distribution volume ratios: PSP-RS, 1.21 [0.10]; PSP-non-RS, 1.12 [0.11]; healthy controls, 1.00 [0.08]; Parkinson disease/multiple system atrophy, 1.03 [0.05]; Alzheimer disease, 1.08 [0.06]). Sensitivity and specificity for detection of PSP-RS vs any control group were 85% and 77%, respectively, when using classification by at least 1 positive target region. Conclusions and Relevance: This multicenter evaluation indicates a value of 18F-PI-2620 to differentiate suspected patients with PSP, potentially facilitating more reliable diagnosis of PSP.

Multimodal assessment of nigrosomal degeneration in Parkinson's disease.

BACKGROUND: Approximately forty percent of all dopaminergic neurons in SNpc are located in five dense neuronal clusters, named nigrosomes. T2- or T2*-weighted images are used to delineate the largest nigrosome, named nigrosome-1. In these images, nigrosome-1 is a hyperintense region in the caudal and dorsal portion of the T2- or T2*-weighted substantia nigra. In PD, nigrosome-1 experiences iron accumulation, which leads to a reduction in T2-weighted hyperintensity. Here, we examine neuromelanin-depletion and iron deposition in regions of interest (ROIs) derived from quantitative-voxel based morphometry (qVBM) on neuromelanin-sensitive images and compare the ROIs with nigrosome-1 identified in T2*-weighted images. METHODS: Neuromelanin-sensitive and multi-echo gradient echo imaging data were obtained. R2* was calculated from multi-echo gradient echo imaging data. qVBM analysis was performed on neuromelanin-sensitive images and restricted to SNpc. Mean neuromelanin-sensitive contrast and R2* was measured from the resulting qVBM clusters. Nigrosome-1 was segmented in T2*-weighted images of control subjects and its location was compared to the spatial location of the qVBM clusters. RESULTS: Two bilateral clusters emerged from the qVBM analysis. These clusters showed reduced neuromelanin-sensitive contrast and increased mean R2* in PD as compared to controls. Cluster-1 from the qVBM analysis was in a similar spatial location as nigrosome-1, as seen in T2*-weighted images. CONCLUSION: qVBM cluster-1 shows reduced neuromelanin-sensitive contrast and is in a similar spatial position as nigrosome-1. This region likely corresponds to nigrosome-1 while the second cluster may correspond to nigrosome-2.

Effectiveness of QSM over R2* in assessment of parkinson's disease - A systematic review.

The incidence and prevalence of Parkinson's (PD) are increasing rapidly in developing countries. PD is difficult to diagnose based on clinical assessment. Presently, magnetic resonance imaging (MRI) methods such as R2* and Quantitative Susceptibility Mapping (QSM) were found to be useful in diagnosing the PD based on the iron deposition in different regions of the brain. The objective of this review was to evaluate the efficacy of QSM over R2* in assessment of PD. A comprehensive literature search was made on PubMed-Medline, CINAHL, Science Direct, Scopus, Web of Science, and the Cochrane library databases for original research articles published between 2000 and 2018. Original articles that reported the efficacy of QSM and R2* in assessment of PD were included. A total of 327 studies were identified in the literature search. However, only ten studies were eligible for analysis. Of the ten studies, five studies compared the accuracy of QSM over R2* in measuring the iron deposition in different regions of brain in PD. Our review found that QSM has better accuracy in identifying iron deposition in PD patients compared to R2*. However, there is discrepancy in the results between MRI Imaging methods and Postmortem studies. Additional longitudinal research studies are needed to provide a strong evidence base for the use of MRI imaging methods such as R2*and QSM in accurately measuring iron deposition in different regions of brain and serve as biomarkers in PD.

Detection and Assessment of α-Synuclein Oligomers in the Urine of Parkinson's Disease Patients.

BACKGROUND: α-Synuclein (α-syn) is a major component of Lewy bodies, a pathologic marker of Parkinson's disease (PD) in post-mortem studies. The use of α-syn as a practical PD biomarker has been investigated by numerous researchers. However, reports of differences in α-syn levels in biofluids, such as cerebrospinal fluid, plasma, and saliva, between PD patients and controls are inconsistent. Recently, the measurement of α-syn oligomer levels has emerged as a novel approach to diagnose PD. OBJECTIVE: Lysates and culture media from two different types of dopaminergic neuronal cells or urine samples from 11 non-PD and 21 PD patients were collected and analyzed. METHODS: We developed and performed an enzyme-linked immuno-absorbent assay (ELISA) to detect various oligomeric α-syn using distinct pairs of antibodies. RESULTS: We validated our ELISA using rotenone-induced alterations of α-syn levels in human dopaminergic neurons. Total urinary α-syn levels, measured using our ELISA method, showed no difference between PD and non-PD individuals, but a higher level of α-syn oligomer recognized by MJFR-14-6-5-2 in PD urine samples was observed. Levels of distinct oligomeric α-syn detected by ASyO5 were lower in PD urine samples. Three different α-syn ELISA results were analyzed with respect to the severity of PD, but only the correlation between total α-syn levels and PD index was significant. CONCLUSION: Our findings suggest that detection of distinct oligomeric formations of α-syn and measurement of their levels in urine might be feasible for use in PD diagnostics.

Positron emission tomography/computed tomography dual imaging using 18-fluorine flurodeoxyglucose and 11C-labeled 2-ß-carbomethoxy-3-ß-(4-fluorophenyl) tropane for the severity assessment of Parkinson disease.

The value of dual imaging mode for the severity assessment of Parkinson disease (PD) is explored by conducting positron emission tomography computed tomography (PET/CT) double imaging using combined 18-fluorine flurodeoxyglucose (F-FDG) brain metabolism and 11C-2ß-carbomethoxy-3ß-(4-fluorophenyl) tropane (C-CFT) brain dopamine transporter (DAT).A total of 102 patients with PD and 50 healthy people in the control group are enrolled for the PET/CT dual imaging of F-FDG brain metabolism and C-CFT brain DAT. The characteristics of F-FDG PET/CT and C-CFT PET/CT imaging are analyzed by delineating the region of interest. Differences in the glucose metabolism and DAT distribution in the basal ganglia of patients with PD and healthy control group in the PET/CT imaging and the radioactive distribution characteristics of cerebral cortex in glucose metabolism imaging are compared. The characteristics of PET/CT imaging of C-CFT brain DAT in the ganglion region in absorbing C-CFT in different PD groups are analyzed.Compared with the healthy control group, changes in the cerebral glucose metabolism in the PD group mainly occur due to the increased symmetry metabolism of the nucleus of bilateral basal ganglia and the decreased metabolism of the cerebral cortex as shown in the F-FDG PET/CT images. With disease progression, the bilateral parietal, frontal, temporal, and occipital leaves showed different degrees of FDG metabolism. Statistically significant difference is observed for theC-CFT absorption among the caudate nucleus and the anterior, middle, and posterior nuclei of the bilateral basal ganglia of the PD and healthy control groups. In the PD group, the bilateral caudate nucleus and the anterior, middle, and posterior parts of the putamen show decreased DAT distribution. Regardless of unilateral or bilateral symptoms, the DAT distribution in the nucleus of the contralateral basal ganglia and in the posterior part of the nucleus is substantially reduced.PET/CT dual imaging by F-FDG PET/CT combined with C-CFT PET/CT features high application value for the severity assessment of PD.