Dopamine Transporter Availability Research Articles

Perivascular Spaces in the Basal Ganglia and Long-term Motor Prognosis in Newly Diagnosed Parkinson Disease.

To investigate the association between enlarged perivascular spaces (PVS) in the basal ganglia (BG-PVS) and long-term motor outcomes in Parkinson disease (PD). We reviewed the medical records of 248 patients with drug-naive early-stage PD (follow-up >3 years, mean age 67.44 ± 8.46 years, 130 female) who underwent brain MRI and dopamine transporter (DAT) scans at initial assessment. The number of baseline enlarged BG-PVS was counted on axial T2-weighted images. Then, patients were divided into 2 groups: a PD group with a low number (0-10) of enlarged PVS (PD-EPVS-; n = 156) and a PD group with a high number (>10) of enlarged PVS (PD-EPVS+; n = 92). We used Cox regression models to compare the levodopa-induced dyskinesia (LID)-, wearing-off-, and freezing of gait (FOG)-free times between groups. We also compared longitudinal increases in levodopa-equivalent dose per body weight between groups using a linear mixed model. Patients in the PD-EPVS+ group were older (72.28 ± 6.07 years) and had greater small vessel disease burden than those in the PD-EPVS- group (64.58 ± 8.38 years). The PD-EPVS+ group exhibited more severely decreased DAT availability in all striatal subregions except the ventral striatum. The risk of FOG was higher in the PD-EPVS+ group, but the risk of LID or wearing-off was comparable between groups. The PD-EPVS+ group required higher doses of dopaminergic medications for effective symptom control compared to the PD-EPVS- group. This study suggests that baseline enlarged BG-PVS can be an indicator of the progression of motor disability in PD.

White Matter Hyperintensities, Dopamine Loss, and Motor Deficits in De Novo Parkinson's Disease.

White matter hyperintensities, prevalent in patients with Parkinson's disease (PD), significantly affect parkinsonian motor symptoms. The objective of this study was to investigate the relationship between white matter hyperintensities and nigrostriatal dopamine depletion and their interaction or mediating effects on motor symptoms in patients with drug-naive early-stage PD. This cross-sectional study enrolled 501 patients with de novo PD who initially underwent [18 F] N-(3-fluoropropyl)-2β-carbonethoxy-3β-(4-iodophenyl) nortropane positron emission tomography and brain magnetic resonance imaging scans between April 2009 and September 2015 in a tertiary-care university hospital. We quantified dopamine transporter availability in each striatal subregion and assessed the severity of periventricular and lobar white matter hyperintensities using the Scheltens scale. The relationship between white matter hyperintensities, dopamine transporter availability in the posterior putamen, and Unified Parkinson's Disease Rating Scale (UPDRS) motor scores was assessed using multivariate linear regression and mediation analyses. Periventricular and frontal white matter hyperintensities were generally associated with dopamine transporter availability in striatal subregions after adjusting for age at symptom onset, sex, disease duration, and vascular risk factors. There was an interaction effect between periventricular white matter hyperintensities and dopamine transporter availability in the posterior putamen for the axial motor score. The effect of white matter hyperintensities on UPDRS total score and bradykinesia subscore was indirectly mediated by dopamine transporter availability in the posterior putamen, whereas the axial sub-score was directly affected by white matter hyperintensities. This study suggests that the detrimental effect of white matter hyperintensities on parkinsonian motor symptoms is more relevant and independent for axial motor impairments in the status of mildly decreased striatal dopamine transporter availability. © 2021 International Parkinson and Movement Disorder Society.

Changes in striatal dopamine transporters in bipolar disorder and valproate treatment.

Previous studies suggested that a disturbance of the dopamine system underlies the pathophysiology of bipolar disorder (BD). In addition, the therapeutic action of medications for treating BD, such as valproate (VPA), might modulate dopamine system activity, but it remains unclear. Here, we aimed to investigate the role of the striatal dopamine transporter (DAT) in BD patients and in social defeat (SD) mice treated with VPA. We enrolled community-dwelling controls (N=18) and BD patients (N=23) who were treated with VPA in a euthymic stage. The striatal DAT availabilities were approached by TRODAT-1 single photon emission computed tomography. We also established a chronic SD mouse model and treated mice with 350mg/kg VPA for 3weeks. Behavioral tests were administered, and striatal DAT expression levels were determined. In humans, the level of striatal DAT availability was significantly higher in euthymic BD patients (1.52±0.17 and 1.37±0.23, p=0.015). Moreover, the level of striatal DAT availability was also negatively correlated with the VPA concentration in BD patients (r=-0.653, p=0.003). In SD mice, the expression of striatal DAT significantly increased (p<0.001), and the SD effect on DAT expression was rescued by VPA treatment. The striatal DAT might play a role in the pathophysiology of BD and in the therapeutic mechanism of VPA. The homeostasis of DAT might represent a new therapeutic strategy for BD patients.

Differential associations of dopamine synthesis capacity with the dopamine transporter and D2 receptor availability as assessed by PET in the living human brain

BackgroundThe dopamine (DA) neurotransmission has been implicated in fundamental brain functions, exemplified by movement controls, reward-seeking, motivation, and cognition. Although dysregulation of DA neurotransmission in the striatum is known to be involved in diverse neuropsychiatric disorders, it is yet to be clarified whether components of the DA transmission, such as synthesis, receptors, and reuptake are coupled with each other to homeostatically maintain the DA neurotransmission. The purpose of this study was to investigate associations of the DA synthesis capacity with the availabilities of DA transporters and D2 receptors in the striatum of healthy subjects. MethodsFirst, we examined correlations between the DA synthesis capacity and DA transporter availability in the caudate and putamen using PET data with L-[β-11C]DOPA and [18F]FE-PE2I, respectively, acquired from our past dual-tracer studies. Next, we investigated relationships between the DA synthesis capacity and D2 receptor availability employing PET data with L-[β-11C]DOPA and [11C]raclopride, respectively, obtained from other previous dual-tracer assays. ResultsWe found a significant positive correlation between the DA synthesis capacity and DA transporter availability in the putamen, while no significant correlations between the DA synthesis capacity and D2 receptor availability in the striatum. ConclusionThe intimate association of the DA synthesis rate with the presynaptic reuptake of DA indicates homeostatic maintenance of the baseline synaptic DA concentration. In contrast, the total abundance of D2 receptors, which consist of presynaptic autoreceptors and postsynaptic modulatory receptors, may not have an immediate relationship to this regulatory mechanism.

The pattern of FP-CIT PET in pure white matter hyperintensities–related vascular parkinsonism

ObjectivesTo determine whether vascular parkinsonism (VaP) patients with visually normal dopamine transporter (DAT) scans have presynaptic dopaminergic depletion. MethodsWe enrolled 23 VaP patients who had parkinsonism, relevant diffuse subcortical white matter hyperintensities (WMH), and visually normal DAT scans, 23 Parkinson's disease (PD) patients, and 31 control subjects. By quantitatively analyzing 18F–N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (18F-FP-CIT) positron emission tomography, we compared the pattern of striatal DAT availability among groups. The discriminatory power of striatal DAT availability to differentiate VaP patients from control subjects or PD patients was assessed using receiver operating characteristics (ROC) analyses. Additionally, correlation analysis was performed to determine whether WMH severity or Unified Parkinson Disease Rating Scale Part III (UPDRS-III) score is related to presynaptic dopaminergic depletion in VaP. ResultsVaP patients exhibited decreased DAT availability in all striatal subregions, including posterior putamen, compared to control subjects. VaP patients and control subjects had similar patterns of anteroposterior and ventrodorsal DAT gradients in caudate and putamen level, but VaP patients exhibited significantly different patterns at putamen level, relative to PD patients. The severity of periventricular WMH was significantly correlated with all substriatal DAT availability in VaP, but not with UPDRS-III scores. The ROC analysis showed that DAT availability in caudate and posterior putamen had a fair discriminatory power when differentiating VaP patients from control subjects. ConclusionsThis study demonstrates that VaP patients with WMH exhibited diffusely decreased DAT availability without any specific regional gradients of DAT patterns distinct from either control subjects or PD patients.

Interaction of dopamine transporter and metabolite ratios underpinning the cognitive dysfunction in patients with carbon monoxide poisoning: A combined SPECT and MRS study

Cognitive dysfunction has been reported in patients with carbon monoxide (CO) poisoning. However, the underpinning mechanism remained unclear. This study examined dopamine transporter (DAT) and metabolite ratios concurrently and their relationships with cognitive dysfunction in CO poisoning. Eighteen suicide attempters with charcoal burning which results in CO poisoning and 18 age- and gender- matched normal controls were recruited. A battery of cognitive assessments including attention, memory, and executive function was administered. Each participant received one single photon emission computed tomography with 99mTc-TRODAT for measuring striatal DAT availability and proton magnetic resonance spectroscopy to determine N-acetyl aspartate/creatine (NAA/Cr), choline-containing compounds/creatine (Cho/Cr) and myo-inositol/creatine (mI/Cr) in the left parietal white matter and mid-occipital gray matter (OGM). CO poisoning patients had significant impairments in memory and executive function. Compared to normal, CO poisoning patients had lower striatal DAT availability, lower NAA/Cr levels in both regions and higher Cho/Cr levels in both regions. In CO poisoning patients, the altered left striatal DAT availability and Cho/Cr level in OGM were significantly associated with executive dysfunction in the expected directions. Moreover, there was a significant interaction between these two imaging indices on their relationships with executive dysfunction and combination of them could adequately predict executive dysfunction in more CO poisoning cases than either alone. The current results suggested that both alterations in DAT availability and metabolite ratios might play crucial roles in executive dysfunction in CO poisoning. This research also highlights the importance of multimodal imaging approaches for studying neurotoxicity effects.

Minimal parkinsonism in the elderly is associated with striatal dopamine loss and pontine structural damage

IntroductionTo investigate whether neurodegeneration underlying Parkinson's disease (PD) accounts for a substantial proportion of cases of minimal parkinsonism in the elderly. MethodsWe recruited 48 consecutive subjects with minimal parkinsonism who visited the clinic with cognitive complaints. All subjects did not show findings compatible with PD on 18F-FP-CIT PET scans, and had no evidence of other neurodegenerative disorders. Striatal dopamine transporter (DAT) availability was quantified, and mean diffusivity (MD) values in the pons were calculated to characterize structural damage using diffusion tensor imaging. Additionally, 35 patients with PD and 21 healthy controls were included as reference groups. ResultsIndividuals with minimal parkinsonism (mean age, 73.23 ± 7.03 years) exhibited mild decrease in DAT availability in the posterior putamen, which was at a level between that of healthy controls and patients with PD. DAT availability in the caudate and anterior putamen was also mildly decreased in the minimal parkinsonism group. Individuals with minimal parkinsonism also tended to have higher MD values in the pons compared to healthy controls. ConclusionsOur results suggest that a substantial proportion of minimal parkinsonism is associated with nigrostriatal dopamine depletion and pontine structural damage, which may be related to the disease process of prodromal PD.

Effect of sex on aging-related decline of dopamine transporter in healthy subjects.

Aging decreases dopamine transporter (DAT) availability of striatum both in humans and rodents. We aimed to investigate the relationship of DAT availabilities from ventral striatum, caudate nucleus, and putamen with aging in healthy subjects. 123I-FP-CIT single photon emission computed tomography (SPECT) was performed in all subjects. Specific binding of 123I-FP-CIT regarding DAT was calculated using a volume-of-interest-based analysis of ventral striatum, caudate nucleus, putamen. The cerebellum was chosen as a reference region. Specific binding ratios (SBRs) were calculated as follows: SBR = (target- cerebellum)/cerebellum. A total of 166 healthy subjects (109 males and 57 females) were included in this study. SBRs of ventral striatum, caudate nucleus, and putamen were negatively correlated with age. In young males, SBRs of ventral striatum and putamen were not correlated with aging. However, SBRs of caudate nucleus showed the trend toward negative correlation with age in the young group. In old males, SBR of caudate nucleus was negatively correlated with age and SBR of ventral striatum showed a trend toward negative correlation with age. Slopes of regression lines were not significantly different according to age groups in ventral striatum, caudate nucleus, or putamen. SBRs of ventral striatum, caudate nucleus, and putamen were negatively correlated with age in young females, but not in old females. Interestingly, slopes of regression line were significantly different between young and old females in ventral striatum, caudate nucleus, and putamen. We have shown that slopes of regression lines of DAT availabilities and age were significantly different between young and old subjects in females, not in males. Therefore, sex has an impact on aging-related decline of striatal DAT availability.

Longitudinal change in dopamine transporter availability in idiopathic REM sleep behavior disorder.

To elucidate longitudinal changes in the dopamine transporter (DAT) availability in association with the prodromal markers in idiopathic REM sleep behavior disorder (iRBD), we analyzed a longitudinal prospective iRBD cohort data. The study cohort consisted of patients with iRBD, individuals with Parkinson disease (PD), and healthy controls. All participants were evaluated for olfaction, neuropsychological tests, and the Movement Disorders Society-Unified Parkinson's Disease Rating Scale and underwent 18F-FP-CIT PET scans every 2 years. We calculated the DAT pattern by performing the principal component analysis of tracer uptakes in 6 striatal regions. DAT patterns in patients with iRBD with baseline hyposmia, constipation, and mild parkinsonian signs distributed toward the PD pattern and clearly distinguished from the healthy control pattern. The DAT pattern moved toward the PD pattern over time in some patients with iRBD during the follow-up, and baseline hyposmia was the only biomarker significantly associated with this change. Baseline PD pattern of DAT predicted 58% of disease converters (hazard ratio 4.95 [95% confidence interval 1.16-21.08]). The combination of hyposmia and baseline PD pattern of DAT predicted 67% of the conversion (hazard ratio 7.89 [confidence interval 1.85-33.69]). The estimated sample size required for a simulated neuroprotective clinical trial was 63 per group when the annual change of DAT pattern was used as an outcome in the subgroup with baseline DAT PD pattern and hyposmia, which is the smallest number reported so far. Baseline and longitudinal monitoring of the DAT pattern can be a useful biomarker in identifying individuals with a high risk of disease conversion and in selecting the potential population for clinical trials in iRBD.

Simplified quantification of [18F]FE-PE2I PET in Parkinson’s disease: Discriminative power, test–retest reliability and longitudinal validity during early peak and late pseudo-equilibrium

Quantification of dopamine transporter (DAT) availability with [18F]FE-PE2I PET enables the detection of presynaptic dopamine deficiency and provides a potential progression marker for Parkinson`s disease (PD). Simplified quantification is feasible, but the time window of short acquisition protocols may have a substantial impact on the reliability of striatal binding estimates. Dynamic [18F]FE-PE2I PET data of cross-sectional (33 PD patients, 24 controls), test–retest (9 patients), and longitudinal (12 patients) cohorts were used to assess the variability and reliability of specific binding ratios (SBR) measured during early peak and late pseudo-equilibrium. Receiver operating characteristics area under the curve (PD vs. controls) was high for early (0.996) and late (0.991) SBR. Early SBR provided more favourable effect size, absolute variability, and standard error of measurement than late SBR (caudate: 1.29 vs. 1.23; 6.9% vs. 9.8%; 0.09 vs. 0.20; putamen: 1.75 vs. 1.67; 7.7% vs. 14.0%; 0.08 vs. 0.17). The annual percentage change was comparable for both time windows (−7.2%–8.5%), but decline was significant only for early SBR. Whereas early and late [18F]FE-PE2I PET acquisitions have similar discriminative power to separate PD patients and controls, the early peak equilibrium acquisition can be recommended if [18F]FE-PE2I is used to measure longitudinal changes of DAT availability.

Clinical and Striatal Dopamine Transporter Predictors of Mild Behavioral Impairment in Drug-Naive Parkinson Disease.

Neuropsychiatric symptoms are important and frequent nonmotor features in Parkinson disease (PD). We explored mild behavioral impairment (MBI) in drug-naive patients with PD and its clinical and dopamine transporter (DAT) correlates. We recruited 275 drug-naive patients with PD who had undergone Unified Parkinson's Disease Rating Scale, a neuropsychological battery, Neuropsychiatric Inventory, and N-(3-[F]fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) PET within 6 months. Patients with PD were divided into groups without MBI (PD-MBI-, n = 186) and with MBI (PD-MBI+, n = 89) according to the Neuropsychiatric Inventory. We performed comparative analysis of DAT availability, cognitive function, and motor deficits between the groups. Mild behavioral impairment was found in 32.4% of PD patients at the time of diagnosis, and affective dysregulation and decreased motivation were the 2 most common neuropsychiatric domains. Dopamine transporter availability in the anterior caudate (odds ratio, 0.60; P = 0.016) and anterior putamen (odds ratio, 0.58; P = 0.008) was associated with the development of MBI in PD. PD-MBI+ group had a lower z-score in memory-related tests and Stroop color reading test than PD-MBI- group. PD-MBI+ group had a higher Unified Parkinson's Disease Rating Scale motor score after controlling for DAT availability in the posterior putamen than PD-MBI- group (P = 0.007). This study suggests that early behavioral impairment is associated with more pathological involvement in the anterior striatum, memory and frontal dysfunction, and motor deficits, which could be regarded as a different phenotype in PD.

Dopamine transporter availability in alcohol and opioid dependent subjects – a 99mTc-TRODAT-1SPECT imaging and genetic association study

Drug dependence associated with increased dopamine neurotransmission and neuroplastic changes is influenced by Dopamine transporters (DAT) which are modulated by genetic and epigenetic factors. This study assesses DAT availability in relation to the 40bp DAT1 VNTR (genetic) and DAT1 promoter methylation (epigenetic) changes in patients with alcohol dependence (AD) and opioid dependence (OD). A total of 60 subjects (n=20 each of AD, OD and controls) were recruited. SPECT/CT imaging using 99mTc-TRODAT-1 was performed for measuring striatal DAT availability and DNA screened to check DAT1promoter methylation and 40bp VNTR polymorphism. SPECT/CT imaging revealed significant decrease in DAT availability in the striatum and putamen and significant increase in DAT1 promoter methylation in AD compared to control and OD. The 40bp VNTR distribution was similar in all three groups with 10repeat and 9repeat alleles being the most common. The AD individuals with DAT1promoter methylation showed significantly lower TRODAT-1 uptake compared to the ones with no methylation. AD individuals homozygous for the 10repeat VNTR also showed reduced DAT availability. This is the first imaging study using 99mTc-TRODAT-1 from India documenting significantly reduced striatal DAT availability, increased DAT methylation and frequency of 10repeat individuals associated with decreased DAT availability in AD.

Dysregulation of oxytocin and dopamine in the corticostriatal circuitry in bipolar II disorder

The oxytocin (OXT) and dopamine systems synergistically facilitate striatal reactivity. Abnormal striatal activation has repeatedly been observed in patients with bipolar disorder (BD); however, such abnormality remains unclear in BD II. Here we aimed to investigate whether the corticostriatal connectivity was altered and the possible relationships among corticostriatal connectivity, OXT, and dopamine systems in BD II. Twenty-five BD II patients, as defined by the DSM-V, and 29 healthy controls (HC) were enrolled in this study. Plasma OXT was measured and striatal dopamine transporter (DAT) availability was assessed using [99mTc]TRODAT-1 single-photon emission computed tomography (SPECT). Brain network functional connectivity (FC) was measured during the resting-state using functional magnetic resonance imaging, and the dorsal caudate (DC) was selected as the seed region. The results showed that the OXT level was significantly lower in the BD II patients, while the striatal DAT availability was not significantly different between the BD II and HC groups. The BD II patients exhibited significantly lower FC between the DC and the executive control network (dorsolateral prefrontal, anterior cingulate cortex, and posterior parietal cortex) as compared with the HC. Only observed in HC, the DC-posterior parietal cortex FC was negatively correlated with the OXT level and striatal DAT availability. Our findings in the HC support a model in which the OXT and dopamine systems act in tandem to regulate corticostriatal circuitry, while the synergistic interaction was perturbed in BD II. Taken together, these results implied a maladaptive neuroplasticity in BD II.

Hopelessness, Dissociative Symptoms, and Suicide Risk in Major Depressive Disorder: Clinical and Biological Correlates.

Background: Major depressive disorder (MDD) has different clinical presentations and is associated with neurobiological alterations. Hopelessness, anhedonia, and dissociation represent some of the most pervasive psychopathological symptoms that often lead to suicidal thoughts, attempts, and actions. To further research on the concept of depression endophenotypes, this study aimed to assess the possible relationships between hopelessness and other clinical and biological correlates (i.e., striatal dopaminergic dysfunction) in depressed patients. Methods: We recruited 51 subjects with MDD. All subjects underwent 123I-FP-CIT SPECT to assess striatal dopamine transporter (DAT) availability and a psychometric evaluation using the psychometric scale to assess depressive, anxious, dissociative, and hopelessness symptoms aside from suicidal ideation. Result: An inverse correlation between the hopelessness score and dopamine transporter availability in all basal ganglia was bilaterally found. (Right Putamen, r = −0.445, p < 0.01; Left Putamen, r = −0.454, p < 0.01; Right Caudate, r = −0.398, p < 0.01; Left Caudate, r = −0.467, p < 0.01) Moreover, a positive correlation was also found between hopelessness and dissociative symptoms. Conclusions: These results provide important evidence on the neurobiological and clinical correlates of different psychopathological symptoms of depression with potential implications in terms of devising more effective treatment programs.

Patterns of striatal dopamine depletion in early Parkinson disease: Prognostic relevance.

To investigate whether the patterns of striatal dopamine depletion on dopamine transporter (DAT) scans could provide information on the long-term prognosis in Parkinson disease (PD). We enrolled 205 drug-naive patients with early-stage PD, who underwent 18F-FP-CIT PET scans at initial assessment and received PD medications for 3 or more years. After quantifying the DAT availability in each striatal subregion, factor analysis was conducted to simplify the identification of striatal dopamine depletion patterns and to yield 4 striatal subregion factors. We assessed the effect of these factors on the development of levodopa-induced dyskinesia (LID), wearing-off, freezing of gait (FOG), and dementia during the follow-up period (6.84 ± 1.80 years). The 4 factors indicated which striatal subregions were relatively preserved: factor 1 (caudate), factor 2 (more-affected sensorimotor striatum), factor 3 (less-affected sensorimotor striatum), and factor 4 (anterior putamen). Cox regression analyses using the composite scores of these striatal subregion factors as covariates demonstrated that selective dopamine depletion in the sensorimotor striatum was associated with a higher risk for developing LID. Selective dopamine loss in the putamen, particularly in the anterior putamen, was associated with early development of wearing-off. Selective involvement of the anterior putamen was associated with a higher risk for dementia conversion. However, the patterns of striatal dopamine depletion did not affect the risk of FOG. These findings suggested that the patterns of striatal dopaminergic denervation, which were estimated by the equation derived from the factor analysis, have a prognostic implication in patients with early-stage PD.

Detection of reduced dopamine transporter availability by 123 I-N-omega-fluoropropyl-2-beta-carbomethoxy-3-beta (4-iodophenyl) nortropane single-photon emission computed tomography in a patient of frontotemporal dementia with motor neuron disease.

Detection of reduced dopamine transporter availability by 123 I-N-omega-fluoropropyl-2-beta-carbomethoxy-3-beta (4-iodophenyl) nortropane single-photon emission computed tomography in a patient of frontotemporal dementia with motor neuron disease.

Areas of white matter hyperintensities and motor symptoms of Parkinson disease.

To determine whether deep white matter and periventricular hyperintensities affect the motor symptoms of Parkinson disease (PD) differently, we analyzed MRI and dopamine transporter imaging. We analyzed the medical records of patients with de novo PD who underwent dopamine transporter PET scanning and MRI at their first visit. Deep white matter and periventricular hyperintensities were scored with a visual rating scale, and motor symptoms were assessed by Unified Parkinson's Disease Rating Scale motor score and tremor, rigidity, bradykinesia, and axial symptom subscores. The influence of white matter hyperintensity on motor symptoms was explored using multivariable linear regression models. A total of 93 patients (mean age, 67.2 ± 9.9 years; 44 male) were included and the mean motor score was 25.0 ± 10.8. Subscores for bradykinesia and axial symptoms were correlated with both deep white matter and periventricular hyperintensities scores. Multivariable linear regression models revealed that deep white matter hyperintensities score was significantly associated with subscore for bradykinesia and periventricular hyperintensities score was associated with subscores for bradykinesia and axial symptoms after adjusting for putaminal dopamine transporter availability and clinical factors. These results demonstrate that deep white matter hyperintensities are associated with bradykinesia and periventricular hyperintensities are associated with bradykinesia and axial symptoms in patients with PD independently of the severity of dopaminergic depletion.

Dysautonomia Is Linked to Striatal Dopamine Deficits and Regional Cerebral Perfusion in Early Parkinson Disease.

The aim of this study was to investigate the association between autonomic dysfunction and striatal dopamine depletion or metabolic changes in de novo Parkinson disease (PD). Based on the Composite Autonomic Severity Score (CASS), patients with de novo PD were classified into PD with (PD-AUT+) and without autonomic dysfunction (PD-AUT-) groups. We compared the dopamine transporter (DAT) availability in the striatum by quantitatively measuring F-FP-CIT PET between both groups. We also assessed the association between DAT availability and the CASS. In addition, we compared regional uptake in early-phase images of F-FP-CIT PET as well as cortical thickness between the PD-AUT+ and PD-AUT- groups. The PD-AUT+ group had significantly lower DAT availability in all striatal subregions than did the PD-AUT- group. The total CASS was significantly correlated with DAT availability in all striatal subregions. In addition, the subscores of the adrenergic component were correlated with DAT availability in all striatal subregions. The subscores of the cardiovagal component were negatively correlated with DAT availability in the caudate and ventral striatum. In early-phase F-FP-CIT PET, the PD-AUT+ group exhibited decreased regional perfusion in the parieto-occipital areas and increased regional perfusion in the pallidothalamic, pontocerebellar, inferior frontal, and primary motor areas compared with the PD-AUT- group. There were no regions of different cortical thickness between the PD groups. The present study revealed that autonomic dysfunction is closely linked to striatal dopamine depletion and prominent PD-related perfusion patterns in de novo PD, suggesting a greater pathological burden in patients with dysautonomia.

Low dopamine transporter binding in the nucleus accumbens in geriatric patients with severe depression.

Dysfunction of dopaminergic neurons in the central nervous system is considered to be related to major depressive disorder (MDD). Especially, MDD in geriatric patients is characterized by anhedonia, which is assumed to be associated with reduced dopamine neurotransmission in the reward system. Dopamine transporter (DAT) is considered to reflect the function of the dopamine nerve system. However, previous DAT imaging studies using single photon emission computed tomography or positron emission tomography (PET) have shown inconsistent results. The radioligand [18 F]FE-PE2I for PET enables more precise evaluation of DAT availability. Hence, we aimed to evaluate the DAT availability in geriatric patients with MDD using [18 F]FE-PE2I. Eleven geriatric patients with severe MDD and 27 healthy controls underwent PET with [18 F]FE-PE2I, which has high affinity and selectivity for DAT. Binding potentials (BPND ) in the striatum (caudate and putamen), nucleus accumbens (NAc), and substantia nigra were calculated. BPND values were compared between MDD patients and healthy controls. MDD patients showed significantly lower DAT BPND in the NAc (P = 0.009), and there was a trend of lower BPND in the putamen (P = 0.032) compared to controls. We found low DAT in the NAc and putamen in geriatric patients with severe MDD, which could be related to dysregulation of the reward system.

Relations of clinical symptoms with dopamine transporter imaging in drug-naïve Parkinson’s disease

ObjectivesThe aim of the present study was to determine the relations of clinical symptoms with nigrostriatal neuron loss in drug-naïve patients with Parkinson’s disease (PD). We examined the severity of motor symptoms and freezing of gait (FOG), falls and overactive bladder (OAB) in PD patients and their relations with striatal dopamine transporter (DAT) binding. Patients and Methods: Thirty-two untreated PD patients (14 men and 18 women with a mean age of 71.4 ± 7.2 years) were included in this study. Clinical assessments were performed by using Unified Parkinson’s Disease Rating Scale (UPDRS) and overactive bladder symptom score (OABSS), and striatal dopamine transporter (DAT) binding was measured by123I-FP-CIT SPECT. Results: The results showed that striatal DAT availability was significantly lower in the high UPDRS motor score group, high akinetic-rigid score group, FOG group, and OAB group than in the low UPDRS motor score group, low akinetic-rigid score group, non-FOG group, and non-OAB group. However, the results also showed that there was no significant difference in striatal DAT availability between the high tremor score group and low tremor score group or between the faller group and non-faller group. Conclusions: The severity of bradykinesia and axial symptoms and the existence of FOG and OAB in untreated PD patients are related to a decrease in striatal DAT availability. Severity of tremors and occurrence of falls are not related to a decrease in striatal DAT availability. The mechanisms underlying the clinical symptoms of PD involve not only dopaminergic pathways but also non-dopaminergic pathways.