Dopamine Transporter Uptake Research Articles

Clinical assessment and striatal dopaminergic activity in healthy controls and patients with Parkinson's disease: a Bayesian approach.

We aimed to evaluate correlations between striatal dopamine transporter (DAT) uptake and clinical assessments in both patients with Parkinson's disease (PD) and healthy controls. This study enrolled 193 healthy controls, and 581 patients with PD. They underwent various clinical assessments and 123I-FP-CIT SPECT scans. After reconstruction, attenuation correction, and normalization of SPECT images, counts were measured from the bilateral caudate and putamen, and the occipital cortex for reference. Count densities for each region were extracted and used to calculate striatal binding ratios (SBRs) for each striatal region. SBR is calculated as (target region/reference region)-1. After logarithmic transformation of striatal SBRs, we analyzed the effects of clinical assessments on striatal SBRs using Bayesian hierarchical modeling. MDS-UPDRS total score, part I, part II, part III, Epworth Sleepiness Scale, REM sleep behavior disorder screening questionnaire, SCOPA-AUT total score were negatively associated with striatal SBR in patients with PD. Also, HVLT recognition discrimination was positively associated with striatal SBR in both healthy controls and patients with PD. In healthy control, MDS-UPDRS part II, MOCA, SCOPA-AUT total score were positively associated with striatal SBR. We demonstrated that motor symptom, sleep disturbance, autonomic symptom, and cognition of patients with PD were associated with striatal dopaminergic activity. In healthy controls, motor symptoms, autonomic symptom, and cognition were associated with striatal dopaminergic activity, some of which showing the opposite direction with patients with PD. This result might provide new insight to underlying mechanism of dopamine system with motor and non-motor assessments.

Differentiating Prodromal Dementia with Lewy Bodies from Prodromal Alzheimer's Disease: A Pragmatic Review for Clinicians.

This pragmatic review synthesises the current understanding of prodromal dementia with Lewy bodies (pDLB) and prodromal Alzheimer's disease (pAD), including clinical presentations, neuropsychological profiles, neuropsychiatric symptoms, biomarkers, and indications for disease management. The core clinical features of dementia with Lewy bodies (DLB)-parkinsonism, complex visual hallucinations, cognitive fluctuations, and REM sleep behaviour disorder are common prodromal symptoms. Supportive clinical features of pDLB include severe neuroleptic sensitivity, as well as autonomic and neuropsychiatric symptoms. The neuropsychological profile in mild cognitive impairment attributable to Lewy body pathology (MCI-LB) tends to include impairment in visuospatial skills and executive functioning, distinguishing it from MCI due to AD, which typically presents with impairment in memory. pDLB may present with cognitive impairment, psychiatric symptoms, and/or recurrent episodes of delirium, indicating that it is not necessarily synonymous with MCI-LB. Imaging, fluid and other biomarkers may play a crucial role in differentiating pDLB from pAD. The current MCI-LB criteria recognise low dopamine transporter uptake using positron emission tomography or single photon emission computed tomography (SPECT), loss of REM atonia on polysomnography, and sympathetic cardiac denervation using meta-iodobenzylguanidine SPECT as indicative biomarkers with slowing of dominant frequency on EEG among others as supportive biomarkers. This review also highlights the emergence of fluid and skin-based biomarkers. There is little research evidence for the treatment of pDLB, but pharmacological and non-pharmacological treatments for DLB may be discussed with patients. Non-pharmacological interventions such as diet, exercise, and cognitive stimulation may provide benefit, while evaluation and management of contributing factors like medications and sleep disturbances are vital. There is a need to expand research across diverse patient populations to address existing disparities in clinical trial participation. In conclusion, an early and accurate diagnosis of pDLB or pAD presents an opportunity for tailored interventions, improved healthcare outcomes, and enhanced quality of life for patients and care partners.

Association of Family History and Polygenic Risk Score With Longitudinal Prognosis in Parkinson Disease.

Evidence suggests that either family history or polygenic risk score (PRS) is associated with developing Parkinson disease (PD). However, little is known about the longitudinal prognosis of PD according to family history and higher PRS. From the Parkinson's Progression Markers Initiative database, 395 patients with PD who followed up for more than 2 years were grouped into those with family history within first-degree, second-degree, and third-degree relatives (N = 127 [32.2%]) vs those without (N = 268 [67.8%]). The PRS of 386 patients was computed using whole-genome sequencing data. Longitudinal assessment of motor, cognition, and imaging based on dopaminergic degeneration was conducted during the regular follow-up period. Effects of family history, PRS, or both on longitudinal changes of cognition, motor severity, and nigrostriatal degeneration were tested using a linear mixed model. The risk of freezing of gait (FOG) according to family history was assessed using the Kaplan-Meier analysis and Cox regression models. During a median follow-up of 9.1 years, PD with positive family history showed a slower decline of caudate dopamine transporter uptake (β estimate of family history × time = 0.02, 95% CI = 0.002-0.036, p = 0.027). Family history of PD and higher PRS were independently associated with a slower decline of Montreal Cognitive Assessment (β estimate of family history × time = 0.12, 95% CI = 0.02-0.22, p = 0.017; β estimate of PRS × time = 0.09, 95% CI = 0.03-0.16, p = 0.006). In those 364 patients without FOG at baseline, PD with positive family history had a lower risk of FOG (hazard ratio of family history = 0.57, 95% CI = 0.38-0.84, p = 0.005). Having a family history of PD predicts slower progression of cognitive decline and caudate dopaminergic degeneration, and less FOG compared with those without a family history independent of PRS. Taken together, information on family history could be used as a proxy for the clinical heterogeneity of PD. The study was registered at clinicaltrials.gov (NCT01141023), and the enrollment began June 1, 2010.

Microstructural alterations in white matter and related neurobiology based on the new clinical subtypes of Parkinson's disease.

The advent of new clinical subtyping systems for Parkinson's disease (PD) has led to the classification of patients into distinct groups: mild motor predominant (PD-MMP), intermediate (PD-IM), and diffuse malignant (PD-DM). Our goal was to evaluate the efficacy of diffusion tensor imaging (DTI) in the early diagnosis, assessment of clinical progression, and prediction of prognosis of these PD subtypes. Additionally, we attempted to understand the pathological mechanisms behind white matter damage using single-photon emission computed tomography (SPECT) and cerebrospinal fluid (CSF) analyses. We classified 135 de novo PD patients based on new clinical criteria and followed them up after 1 year, along with 45 healthy controls (HCs). We utilized tract-based spatial statistics to assess the microstructural changes of white matter at baseline and employed multiple linear regression to examine the associations between DTI metrics and clinical data at baseline and after follow-up. Compared to HCs, patients with the PD-DM subtype demonstrated reduced fractional anisotropy (FA), increased axial diffusivity (AD), and elevated radial diffusivity (RD) at baseline. The FA and RD values correlated with the severity of motor symptoms, with RD also linked to cognitive performance. Changes in FA over time were found to be in sync with changes in motor scores and global composite outcome measures. Furthermore, baseline AD values and their rate of change were related to alterations in semantic verbal fluency. We also discovered the relationship between FA values and the levels of α-synuclein and β-amyloid. Reduced dopamine transporter uptake in the left putamen correlated with RD values in superficial white matter, motor symptoms, and autonomic dysfunction at baseline as well as cognitive impairments after 1 year. The PD-DM subtype is characterized by severe clinical symptoms and a faster progression when compared to the other subtypes. DTI, a well-established technique, facilitates the early identification of white matter damage, elucidates the pathophysiological mechanisms of disease progression, and predicts cognitively related outcomes. The results of SPECT and CSF analyses can be used to explain the specific pattern of white matter damage in patients with the PD-DM subtype.

Clinical correlates of Dopamine transporter imaging and EEG biomarkers in Dementia with Lewy bodies

AbstractBackgroundDiagnostic value of dopamine transporter (DAT) imaging and electroencephalography (EEG) biomarkers in Dementia with Lewy bodies (DLB) is well studied, but their relationships with clinical symptoms in DLB are not elusive. We investigated the association between DAT imaging and EEG biomarkers and clinical characteristics of DLB.MethodWe evaluated the 120 patients with DLB retrospectively. Quantitative analysis of DAT imaging was performed and uptakes for caudate, putamen, and ventral striatum (VST) were assessed. Frequency of posterior dominant rhythm and theta/beta ratio (TBR) were used as EEG biomarkers. Four core clinical features of DLB were assessed. Firstly, correlation analysis between biomarkers and clinical symptoms were assessed. Regression analyses with significantly correlated biomarkers as model variable were performed to investigate the association between clinical characteristics and biomarkers. Age, sex, and education were used as covariates.ResultParietal TBR (B = 0.498, P = 0.023) and putaminal DAT uptake (B = ‐0.609, P = 0.010) were related to the presence of fluctuation. The severity of visual hallucination was associated with the higher parietal TBR (B = 0.391, P = 0.045) and lower DAT uptake in putamen (B = ‐0.520, P = 0.010) and. Putaminal DAT uptake was related to the presence of REM sleep behavior disorder (B = ‐0.646, P = 0.010). Severity of parkinsonism was associated with the frontal TBR (B = 3.353, P < 0.001).ConclusionDAT imaging and EEG biomarkers were related to the clinical symptoms in DLB differently. In addition, TBR reflects characteristics of DLB better than posterior slow activity.

The Role of Dual-Phase 18 F-FP-CIT PET to Early Diagnosis of Corticobasal Syndrome.

Corticobasal syndrome (CBS) is a neurodegeneration characterized by asymmetric parkinsonism, dystonia, myoclonus, and apraxia. In the early stage, CBS presents with asymmetric parkinsonism and cortical symptoms (apraxia and alien hand), and neuroimaging finding is often vague, making early clinical differentiation from idiopathic Parkinson disease (IPD) challenging. This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter (DAT) uptake using dual-phase FP-CIT PET in discriminating between CBS and IPD at early stage. The study enrolled clinically diagnosed CBS (n = 11) and IPD (n = 22) patients (age and sex matched). All participants underwent dual-phase 18 F-FP-CIT PET, and regional SUV ratio (SUVR) was obtained by semiquantitative analysis. The early perfusion imaging and DAT imaging were compared between groups. The regional SUVRs (early phase) of the frontal lobe, thalamus, cingulate, and caudate were significantly lower in patients with CBS, whereas the SUVR of occipital lobe was lower in the IPD group. The CBS group exhibited more prominent asymmetry than the IPD group, particularly in the perirolandic area, superior frontal gyrus, and anterior parietal lobe in early phase PET. Striatal DAT uptake (delayed phase) revealed that the caudate showed lower SUVR and prominent asymmetry in the CBS group, and the caudate-to-putamen ratio (CP ratio) was significantly lower in CBS patients ( P < 0.001). Among the parameters (early and delayed), the CP ratio in DAT exhibited the most powerful discriminative power from receiver operating characteristic curve comparison (area under curve = 0.983). This study demonstrated that the dual-phase FP-CIT PET is useful in differentiating CBS and IPD in the early stage of the disease, and a lower CP ratio of DAT imaging is highly informative for distinguishing between corticobasal degeneration and IPD.

Prognostic significance of peripheral neutrophils and lymphocytes in early untreated Parkinson’s disease: an 8-year follow-up study

BackgroundTo explore whether peripheral blood neutrophils and lymphocytes are associated with longitudinal motor and cognitive decline in patients with early Parkinson’s disease (PD) and, to uncover the disease-specific mechanisms underlying...

Association between longitudinal changes in striatal dopamine transporter uptake and clinical features of dementia with Lewy bodies.

It is widely known that there is low striatal 123 I-2β-Carbomethoxy-3β-(4-iodophenyl)-N-(3- fluoropropyl) nortropane (123 I-FP-CIT) dopamine transporter single photon emission tomography (DaT-SPECT) uptake in patients with dementia with Lewy bodies (DLB). No studies to date have analyzed the association between longitudinal changes of clinical features and DaT uptake in patients with Parkinson syndrome, particularly those with DLB. The aim of this study was to investigate the association between the longitudinal changes in DaT uptake and the severity of parkinsonism and cognitive function in DLB patients. A total of 35 outpatients with probable DLB who underwent DaT-SPECT twice (at the initial examination and the follow-up period) in the Memory Disorder Clinic at the Department of Geriatric Medicine, Tokyo Medical University, were enrolled in this study between April 2014 and September 2020. The correlation between annual changes in DaT uptake and clinical features (cognitive function decline and parkinsonism) of the patients was analyzed. A significant correlation was detected between annual changes in parkinsonism symptom severity and DaT uptake in the left posterior putamen (r = -0.39, P = 0.03), and between Mini-Mental State Examination scores and DaT uptake in all regions except the right posterior putamen (P < 0.05) in patients with DLB. Our results suggested that the pathway from the ventrolateral tier of the substantia nigra to the putamen might be more crucial for motor function than other pathways, not only in Parkinson's disease but also in DLB.

Association between regular physical activity and biomarker changes in early Parkinson's disease patients

IntroductionPhysical activity benefits patients with Parkinson's disease (PD) and is assumed to possess disease-modifying potential. PD-related biomarkers, such as dopamine transporter (DAT) imaging and cerebrospinal fluid (CSF) α-synuclein (α-syn) and amyloid β (Aβ), correlate with disease severity and, to some extent, reflect disease progression and pathology. However, the association between regular physical activity and PD biomarker changes remains unknown. This study aimed to investigate the association between physical activity and longitudinal trajectories of PD biomarkers. MethodsThis retrospective study included 444 patients with a median follow-up time of 5 years from the Parkinson's Progression Markers Initiative cohort. Data collection included physical activity as scaled by the Physical Activity Scale for the Elderly questionnaire, dopamine transporter imaging, CSF assessment, and serum biomarkers. We analyzed the data using a linear mixed regression model. ResultsRegular physical activity was associated with a slower decline of DAT uptake in the caudate (β = 0.063, p = 0.011) and the putamen (β = 0.062, p = 0.023). No association was detected between regular physical activity and CSF, as well as serum biomarkers. ConclusionRegular physical activity is associated with favorable PD biomarker progression, indicating a potential disease-modifying effect.

Striatal Dopamine Transporter Uptake, Parkinsonism, and Cognition in Alzheimer's Disease.

The correlates of motor parkinsonism in Alzheimer's disease (AD) remains controversial. We evaluated the effects of nigrostriatal dopaminergic degeneration on parkinsonism and cognition in biomarker-validated patients with AD. This study recruited 116 patients with AD who underwent dual-phase 18 F-N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane PET, 18 F-Florbetaben PET, 3-Tesla brain MRI, Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological tests. The mean cortical thickness in the frontal, temporal, parietal, and occipital cortices, and the dopamine transporter (DAT) uptake in the caudate, anterior/posterior putamen, and substantia nigra were quantified. We investigated the relationship between DAT uptake, mean lobar cortical thickness, UPDRS motor score, and cognition using general linear models (GLMs) after controlling for age, sex, education, intracranial volume, and deep and periventricular white matter hyperintensities. A path analysis was performed for the UPDRS motor score with the same covariates. Path analysis and multivariable GLM for UPDRS motor score showed that lower caudate DAT uptake was directly associated with a higher UPDRS motor score, whereas caudate DAT uptake confounded the association between mean frontal/parietal thickness and UPDRS motor score. Multivariable GLMs for cognitive scores showed that lower caudate DAT uptake was associated with visuospatial/executive dysfunction independent of mean frontal or parietal thickness. Nigrostriatal dopaminergic dysfunction is associated with parkinsonism and visuospatial/executive dysfunction in patients with AD.

Glymphatic function assessment in Parkinson's disease using diffusion tensor image analysis along the perivascular space

IntroductionGlymphatic dysfunction can contribute to α-synucleinopathies. We examined glymphatic function in idiopathic Parkinson's disease (PD) utilizing Diffusion Tensor Image Analysis aLong the Perivascular Space (DTI-ALPS). MethodsThis study enrolled consecutive patients diagnosed with de novo PD between June 2017 and March 2019 who underwent brain DTI with concurrent 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT) SPECT, and age- and sex-matched controls. From DTI-ALPS, the ALPS-index was calculated as a ratio of diffusivities along the x-axis in the region of neural fibers passing vertically to the diffusivities perpendicular to them, which reflected perivascular water motion at the lateral ventricular body level. The ALPS-index of the PD and control groups was compared using Student's t-test; its correlations with clinical scores for motor and cognition (UPDRS-III, MMSE, and MoCA) and striatal dopamine transporter uptake measured by 123I-FP-CIT specific binding ratios (SBRs) were examined using a correlation coefficient. ResultsIn all, 54 patients in the de novo PD group (31 women, 23 men; mean age, 68.9 ± 9.4 years) and 54 in the control group (mean age, 69.0 ± 10.5 years) were included. The ALPS-index was lower in the PD group than in the controls (1.51 ± 0.22 versus 1.66 ± 0.20; P < 0.001). In the PD group, the ALPS-index negatively correlated with the UPDRS-III score (r = −0.526), and positively correlated with the MMSE (r = 0.377) and MoCA scores (r = 0.382) (all, P < 0.05). No correlation was observed between the ALPS-index and striatal 123I-FP-CIT SBRs (P > 0.05). ConclusionsDTI-ALPS can reveal glymphatic dysfunction in patients with PD, whose severity correlated with motor and cognitive dysfunction, but not striatal dopamine transporter uptake.

Antihypertensive drugs may not delay the symptom progression of Parkinson’s disease: A 2-year follow-up study

BackgroundParkinson's disease (PD) is one of the most common neurodegenerative disease, and half of PD patients have hypertension as well. The effect of antihypertensive drugs on the progression of PD has been less studied. The focus of this study was on the changes in dopamine transporter (DAT) levels to assess the effect of antihypertensive drugs on the progression of PD. MethodsData from 321 drug-naïve patients from the Parkinson's Disease Progression Marker Initiative (PPMI) were collected over a 2-year period. Patients were divided into the PD with arterial hypertension (AH) group (102 cases) with antihypertensive drugs, the PD with other cardiovascular risk factors (CVRFs) group (60 cases) with antidiabetic and/or lipid-lowering drugs, and the pure PD group (159 cases) without CVRFs. The Movement Disorder Society Sponsored Revision Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Hoehn-Yahr (H&Y) stage were used to assess progression. DAT semiquantitative values were used to evaluate damage to dopaminergic neurons in the substantia nigra, including the contralateral and ipsilateral count density ratio and asymmetry index. ResultsThere were no significant differences among the three groups in MDS-UPDRS score and H&Y stage. Changes in DAT levels among the three groups were without distinct differences in the first year and second year. In each group, DAT decreased more in the first year than in the second year. There was no decrease in DAT uptake in the PD with AH group compared with the other groups during the follow-up period. ConclusionsThere is no evidence that antihypertensive drugs can delay PD progression within 2 years.

WITHDRAWN: Association between regular physical activity and biomarker changes in early Parkinson's disease patients

Physical activity benefits patients with Parkinson's disease (PD) and is assumed to possess disease-modifying potential. PD-related biomarkers, such as dopamine transporter (DAT) imaging and cerebrospinal fluid (CSF) α-synuclein (α-syn) and amyloid β (Aβ), correlate with disease severity and, to some extent, reflect disease progression and pathology. However, the association between regular physical activity and PD biomarker changes remains unknown. This study aimed to investigate the association between physical activity and longitudinal trajectories of PD biomarkers. This retrospective study included 444 patients with a median follow-up time of 5 years from the Parkinson's Progression Markers Initiative cohort. Data collection included physical activity as scaled by the Physical Activity Scale for the Elderly questionnaire, dopamine transporter imaging, CSF assessment, and serum biomarkers. We analyzed the data using a linear mixed regression model. Regular physical activity was associated with a slower decline of DAT uptake in the caudate (β=0.063, p=0.011) and the putamen (β=0.062, p=0.023). No association was detected between regular physical activity and CSF, as well as serum biomarkers. Regular physical activity is associated with favorable PD biomarker progression, indicating a potential disease-modifying effect.

Substantia nigral dopamine transporter uptake in dementia with Lewy bodies

Nigrostriatal dopaminergic degeneration is a pathological hallmark of dementia with Lewy bodies (DLB). To identify the subregional dopamine transporter (DAT) uptake patterns that improve the diagnostic accuracy of DLB, we analyzed N-(3-[18F] fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane (FP-CIT) PET in 51 patients with DLB, in 36 patients with mild cognitive impairment with Lewy body (MCI-LB), and in 40 healthy controls (HCs). In addition to a high affinity for DAT, FP-CIT show a modest affinity to serotonin or norepinephrine transporters. Specific binding ratios (SBRs) of the nigrostriatal subregions were transformed to age-adjusted z-scores (zSBR) based on HCs. The diagnostic accuracy of subregional zSBRs were tested using receiver operating characteristic (ROC) curve analyses separately for MCI-LB and DLB versus HCs. Then, the effect of subregional zSBRs on the presence of clinical features and gray matter (GM) density were evaluated in all patients with MCI-LB or DLB as a group. ROC curve analyses showed that the diagnostic accuracy of DLB based on the zSBR of substantia nigra (area under the curve [AUC], 0.90) or those for MCI-LB (AUC, 0.87) were significantly higher than that based on the zSBR of posterior putamen for DLB (AUC, 0.72) or MCI-LB (AUC, 0.65). Lower zSBRs in nigrostriatal regions were associated with visual hallucination, severe parkinsonism, and cognitive dysfunction, while lower zSBR of substantia nigra was associated with widespread GM atrophy in DLB and MCI-LB patients. Taken together, our results suggest that evaluation of nigral DAT uptake may increase the diagnostic accuracy of DLB and MCI-LB than other striatal regions.

Neurofilament light chain and cardiac MIBG uptake as predictors for phenoconversion in isolated REM sleep behavior disorder.

Isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD) is considered as a prodromal stage of either multiple system atrophy (MSA) or Lewy body disease (LBD; Parkinson's disease and dementia with Lewy bodies). However, current knowledge is limited in predicting and differentiating the type of future phenoconversion in iRBD patients. We investigated the role of plasma neurofilament light chain (NfL) and cardiac metaiodobenzylguanidine (MIBG) uptake as predictors for phenoconversion. Forty patients with iRBD were enrolled between April 2018 and October 2019 and prospectively followed every 3months to determine phenoconversion to either MSA or LBD. Plasma NfL levels were measured at enrollment. Cardiac MIBG uptake and striatal dopamine transporter uptake were assessed at baseline. Patients were followed for a median of 2.92years. Four patients converted to MSA and 7 to LBD. Plasma NfL level at baseline was significantly higher in future MSA-converters (median 23.2pg/mL) when compared with the rest of the samples (median 14.1pg/mL, p = 0.003). NfL level above 21.3pg/mL predicted phenoconversion to MSA with the sensitivity of 100% and specificity of 94.3%. Baseline MIBG heart-to-mediastinum ratio of LBD-converters (median 1.10) was significantly lower when compared with the rest (median 2.00, p < 0.001). Heart-to-mediastinum ratio below 1.545 predicted phenoconversion to LBD with the sensitivity of 100% and specificity of 92.9%. Plasma NfL and cardiac MIBG uptake may be useful biomarkers in predicting phenoconversion of iRBD. Elevated plasma NfL levels may suggest imminent phenoconversion to MSA, whereas low cardiac MIBG uptake suggests phenoconversion to LBD.

Deep learning regressor model based on nigrosome MRI in Parkinson syndrome effectively predicts striatal dopamine transporter-SPECT uptake

PurposeNigrosome imaging using susceptibility-weightedimaging (SWI) and dopamine transporter imaging using 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT) single-photon emission computerized tomography (SPECT) can evaluate Parkinsonism. Nigral hyperintensity from nigrosome-1 and striatal dopamine transporter uptake are reduced in Parkinsonism; however, quantification is only possible with SPECT. Here, we aimed to develop a deep-learning-based regressor model that can predict striatal 123I-FP-CIT uptake on nigrosome magnetic resonance imaging (MRI) as a biomarker for Parkinsonism.MethodsBetween February 2017 and December 2018, participants who underwent 3 T brain MRI including SWI and 123I-FP-CIT SPECT based on suspected Parkinsonism were included. Two neuroradiologists evaluated the nigral hyperintensity and annotated the centroids of nigrosome-1 structures. We used a convolutional neural network-based regression model to predict striatal specific binding ratios (SBRs) measured via SPECT using the cropped nigrosome images. The correlation between measured and predicted SBRs was evaluated.ResultsWe included 367 participants (203 women (55.3%); age, 69.0 ± 9.2 [range, 39–88] years). Random data from 293 participants (80%) were used for training. In the test set (74 participants [20%]), the measured and predicted 123I-FP-CIT SBRs were significantly lower with the loss of nigral hyperintensity (2.31 ± 0.85 vs. 2.44 ± 0.90) than with intact nigral hyperintensity (4.16 ± 1.24 vs. 4.21 ± 1.35, P < 0.01). The sorted measured 123I-FP-CIT SBRs and the corresponding predicted values were significantly and positively correlated (ρc = 0.7443; 95% confidence interval, 0.6216–0.8314; P < 0.01).ConclusionA deep learning-based regressor model effectively predicted striatal 123I-FP-CIT SBRs based on nigrosome MRI with high correlation using manually-measured values, enabling nigrosome MRI as a biomarker for nigrostriatal dopaminergic degeneration in Parkinsonism.

Extra-Basal Ganglia Brain Structures Are Related to Motor Reserve in Parkinson's Disease.

The "motor reserve" is an emerging concept based on the discrepancy between the severity of parkinsonism and dopaminergic degeneration; however, the related brain structures have not yet been elucidated. We investigated brain structures relevant to the motor reserve in Parkinson's disease (PD) in this study. Patients with drug-naïve, early PD were enrolled, who then underwent dopamine transporter (DAT) scan and diffusion tensor imaging (DTI). The severity of motor symptoms was evaluated with the Unified Parkinson's Disease Rating Scale score of bradykinesia and rigidity on the more affected side and dopaminergic degeneration of DAT uptake of the more affected putamen. Individual motor reserve estimate (MRE) was evaluated based on the discrepancy between the severity of motor symptoms and dopaminergic degeneration. Using DTI and the Brainnetome atlas, brain structures correlated with MRE were identified. We enrolled 193 patients with drug-naïve PD (mean disease duration of 15.6±13.2 months), and the MRE successfully predicted the increase of levodopa equivalent dose after two years. In the DTI analysis, fractional anisotropy values of medial, inferior frontal, and temporal lobes, limbic structures, nucleus accumbens, and thalamus were positively correlated with the MRE, while no brain structures were correlated with mean diffusivity. Additionally, degree centrality derived from the structural connectivity of the frontal and temporal lobes and limbic structures was positively correlated with the MRE. Our results show empirical evidence for MR in PD and brain structures relevant to MR, particularly, the extra-basal ganglia system including the limbic and frontal structures.

Longitudinal changes in dopamine transporter uptake scans in progressive apraxia of speech

PurposeTo describe qualitative and quantitative longitudinal changes in dopamine transporter uptake (DaT) scan findings in progressive apraxia of speech (PAOS) patients. MethodsDaTQUANT software was used to quantify uptake in the left and right caudate and putamen in DaT scans of 39 patients with PAOS, 19 with repeat scans. Clinical radiologic impressions were used as the gold standard for evaluating whether quantitative measures (z-score of left and right putamen and caudate uptake) aligned with gestalt impressions of DaT abnormalities and clinical impairments, cross-sectionally. Measures at first and last available DaT were used to evaluate change over time and the influence of qualitative abnormality at first visit on change over time. ResultsCross-sectionally, 16/39 patients had abnormal DaT scans on visual read, with differences in all quantitative DaT measures between those with (ab)normal scans, but without differences in any clinical measures (apraxia of speech, aphasia, or parkinsonism). Three patients that had normal DaT scans at baseline were read as abnormal at subsequent visits, with coinciding change in quantitative measures. At the group level, across the 19 patients with repeat imaging, no statistical change in left or right caudate or putamen scores was observed despite progression of clinical indices. Abnormality at first visit did not statistically influence the rate of change over time, although trends were observed. ConclusionsApproximately 40–50% of patients with PAOS have or will develop DaT scans that may be visually read as abnormal. Quantitative measures of DaT match visual reads cross-sectionally, but may not map to clinical progression, including of parkinsonism, observed in these patients.

Use of 99mTc-Trodat-1 SPECT to evaluate the efficacy of deep brain stimulation in Parkinson's disease.

This study aimed to explore the availability of striatal dopamine transporter (DAT) after deep brain stimulation (DBS) by single photon emission computed tomography (SPECT) using technetium-99m-labeled tropane derivative (99mTc-Trodat-1). In this cohort, 28 patients with PD were enrolled (including 18 males and 10 females). Among these patients, the age range was 55-75 years. All patients referred for optimized DBS programming were recruited for 99mTc-Trodat-1 imaging and symptom assessment. Dopamine transporter SPECT was performed under medication-off state before DBS and at the 6th month after DBS, respectively. The clinical scales including Unified Parkinson Disease Rating Scale (UPDRS), Modified Hoehn & Yahr Scale (MHYS) and Ability of Daily Life Scale (ADLS) were carried out before DBS and at 6 months after DBS under medication-on and medication-off, respectively. Dopamine transporter availability was assessed based on DAT SPECT. In addition, the correlation between DAT availability and clinical scales was investigated. The data were analyzed using SPSS 23.0. The mean UPDRS total, MHYS and ADLS scores were 62.36, 2.23 and 42.07 under medication-on, respectively. The medication improvement rate of UPDRS total, MHYS and ADLS scores were 27.55%, 21.88% and 54.19%, respectively. Interestingly, we found PD patients with MHYS grade I usually presented unilateral symptoms, but DAT imaging showed that DAT uptake of the bilateral striatum was lower than that of the normal and the S-value of the contralateral side was significantly lower than that of the ipsilateral side. Furthermore, we found that DBS can improve the laterality of symptoms. The DBS improvement rate of UPDRS total scores, ADLS scores and DAT S-value were 37.65%, 72.51% and 18.21%, respectively. The symptom laterality was significantly correlated with the DAT S-value at baseline and at 6 months after DBS (r=0.63, 0.69 and 0.66, 0.75). The dosage of levodopa was 696.43±146.52 and was 455.36±107.44 before DBS surgery and at DBS-on, respectively. Deep brain stimulation can significantly improve the symptom of PD. Dopamine transporter S-value was well correlated with the change of symptoms laterality. Therefore, DAT imaging can be used to diagnose PD in the early stage and to evaluate the curative effect of DBS. However, the validation of this result requires further study.

Dual-phase 18 F-FP-CIT positron emission tomography and cardiac 123 I-MIBG scintigraphy of Parkinson's disease patients with GBA mutations: evidence of the body-first type?

Parkinson's disease (PD) with glucocerebrosidase (GBA) gene mutation (GBA-PD) is known to show more rapid clinical progression than sporadic PD without GBA mutation (sPD). This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter uptake and cardiac meta-iodobenzylguanidine (MIBG) uptake of GBA-PD in comparison to sPD. Through next-generation sequencing analysis targeting 41 genes, a total of 16 GBA-PD and 24 sPD patients (sex, age matched) were enrolled in the study, and the clinical, dual-phase [18 F]-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (1 8 F-FP-CIT) positron emission tomography (PET)and cardiac 123 I-MIBG scintigraphy results were compared between the two groups. The GBA-PD group had higher rates of rapid eye movement sleep behavior disorder, orthostatic hypotension and neuropsychiatric symptoms than the sPD group. Early-phase 18 F-FP-CIT PETshowed significantly lower standard uptake value ratio on bilateral posterior parietal cortex (0.94 ± 0.05 vs. 1.02 ± 0.04, p=0.011) and part of the occipital cortex (p < 0.05) in the GBA-PD group than the sPD group. In striatal dopamine transporter uptake, the regional standard uptake value ratio, asymmetry index and caudate-to-putamen ratio were similar between the two groups. The GBA-PD group had a lower heart-to-mediastinum uptake ratio in 123 I-MIBG scintigraphy than the sPD group. The GBA-PD patients showed decreased regional perfusion in the bilateral posterior parietal and occipital cortex. Cardiac sympathetic denervation and non-motor symptoms (orthostatic hypotension, rapid eye movement sleep behavior disorder) were more common in GBA-PD than sPD. These findings suggest that GBA-PD patients have more widespread peripheral (extranigral) α-synuclein accumulation, representing a body-first PD subtype.