Dopamine Transporter Uptake Research Articles

Magnetic susceptibility components reveal different aspects of neurodegeneration in alpha-synucleinopathies.

Nigrostriatal dopaminergic degeneration in alpha-synucleinopathies is indirectly reflected by low dopamine transporter (DaT) uptake through [123I]FP-CIT-SPECT. Bulk magnetic susceptibility (χ) in the substantia nigra, from MRI-based quantitative susceptibility mapping (QSM), is a potential biomarker of nigrostriatal degeneration, however, QSM cannot disentangle paramagnetic (e.g. iron) and diamagnetic (e.g. myelin) sources. Using the susceptibility source-separation technique DECOMPOSE, paramagnetic component susceptibility (PCS) and diamagnetic component susceptibility (DCS) were studied in prodromal and overt alpha-synucleinopathies, and their relationships with DaT-SPECT specific binding ratio (SBR) and clinical scores. 78 participants were included (23 controls, 30 prodromal and 25 overt alpha-synucleinopathies). Prodromal patients were subdivided into groups with positive or negative DaT-SPECT (SBR Z-scores below or above -1, respectively). Correlations of putamen and caudate SBR Z-scores with PCS and DCS in the substantia nigra, putamen, and caudate were investigated. Increased PCS was observed in the substantia nigra of prodromal alpha-synucleinopathy patients with positive DaT-SPECT compared to controls and prodromal patients with negative DaT-SPECT. SBR Z-scores in the putamen correlated with increased PCS in the substantia nigra and reduced |DCS| in the putamen, which may reflect dopaminergic degeneration ascribable to iron accumulation and nigrostriatal neuron axonal loss, respectively.

Cerebrospinal fluid tau and disease progression in early Parkinson's disease: an 8-year longitudinal study.

To explore whether CSF phosphorylated tau-181 (P-tau181) and total tau (T-tau) are associated with disease progression in early PD patients. We analyzed 8-year longitudinal clinical data from 368 early, drug-naive PD patients and 185 matched controls from the Parkinson's Progression Markers Initiative cohort. CSF P-tau181 and T-tau were measured over 5years, while CSF α-synuclein was measured over 3years. Dopamine transporter (DAT) imaging was performed at baseline and at 1, 2, and 4years. PD patients exhibited significantly lower CSF P-tau181, T-tau and P-tau181/T-tau ratio than controls at each visit. Higher baseline CSF P-tau181 predicted greater increases in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III (estimate: 0.067, P < 0.001) and Montreal Cognitive Assessment (MoCA) scores (estimate: -0.010, P = 0.009). Similarly, higher baseline CSF T-tau predicted greater increases in MDS-UPDRS III (estimate: 0.005, P < 0.001) and MoCA scores (estimate: -0.001, P = 0.013). Higher baseline P-tau181/T-tau ratio predicted greater increases in MDS-UPDRS III (estimate: 0.552, P < 0.001) but was not significantly associated with changes in MoCA scores (estimate: -0.052, P = 0.114). CSF P-tau181 (estimate = 84.889, P < 0.001), T-tau (estimate = 8.297, P < 0.001) and P-tau181/T-tau ratio (estimate = 263.425, P < 0.001) were positively correlated with CSF α-synuclein but not correlated with striatal DAT uptake. Elevated baseline CSF P-tau181, T-tau and P-tau181/T-tau ratio in early PD patients predict accelerated motor deterioration, with P-tau181 and T-tau also predicting cognitive decline, potentially through interactions with α-synuclein. However, the direct role of tau on nigrostriatal dopaminergic degeneration remains uncertain.

Gastric emptying time and its correlation with cardiac MIBG in body-first and brain-first subtype Parkinson's disease.

Recently, "body-first" and "brain-first" subtype in Parkinson's disease (PD) was proposed based on the propagation of α-synuclein. In isolated RBD considered asa premotor stage of body-first PD, α-synuclein was supposed to originate in the enteric nervous system and spreads via autonomic nervous system. Therefore, we hypothesized that body-first PD is more likely to have a delayed gastric emptying time and reduced cardiac sympathetic denervation. In this study, we aimed to assess gastric motility and its correlation with cardiac sympathetic denervation, dopamine transporter uptake in PD with the body-first PD in comparison with brain-first PD. We investigated gastric scintigraphy, dual-phase 18F-FP-CIT PET, and cardiac MIBG scintigraphy in patients with PD. Based on the presence of RBD and delayed H/M ratio in MIBG scintigraphy, we classified patients into the body-first PD and brain-first PD groups. Gastric emptying time (GET) was assessed by dynamic gastric scintigraphy, and half-emptying time (T1/2) was measured. A total of 18 PDpatients (mean age 68.8) were classified into body-first PD group (n = 10) and brain-first PD group (n = 8). Delayed GET was more prevalent in body-first PD group compared to brain-first PD (T1/2 > 110 min, 90.0 vs 37.5%, p = 0.043). Striatal dopamine depletion was similar between groups and no significant correlation with T1/2. Washout rate of cardiac MIBG showed a tendency of correlation with T1/2 (r = 0.454, p = 0.077). This study showed that body-first PD may be associated with a higher prevalence of delayed gastric emptying time compared to the brain-first PD, suggesting higher burden of gastrointestinal dysmotility in brain-first PD.

Neuroanatomical and clinical correlates of prodromal dementia with Lewy bodies: a systematic literature review of neuroimaging findings.

Prodromal Dementia with Lewy bodies (pro-DLB) has been recently defined; however, the neuroanatomical and functional correlates of this stage have not yet been univocally established. This study aimed to systematically review neuroimaging findings focused on pro-DLB. A literature search of works employing MRI, PET, and SPECT was performed. Forty records were included: 15 studies assessed gray matter (GM) and white matter (WM) integrity, and 31 investigated metabolism, perfusion, and resting-state connectivity. Results showed that, in pro-DLB, frontal lobe areas were characterized by decreased function, cortical atrophy, and WM damage. Volumetric reductions were found in the insula, which also showed heightened metabolism. A pattern of hypofunction and structural damage was observed in the lateral and ventral temporal lobe; instead, the parahippocampal cortex and hippocampus exhibited greater function. Hypofunction marked parietal and occipital regions, with additional atrophy in the medial occipital lobe and posterior parietal cortex. Subcortically, atrophy and microstructural damage in the nucleus basalis of Meynert were reported, and dopamine transporter uptake was reduced in the basal ganglia. Overall, structural and functional damage was already present in pro-DLB and was coherent with the possible clinical onset. Frontal and parieto-occipital alterations may be associated with deficits in attention and executive functions and in visuo-perceptual/visuo-spatial abilities, respectively. Degeneration of cholinergic and dopaminergic transmission appeared substantial at this disease stage. This review provided an updated and more precise depiction of the brain alterations that are specific to pro-DLB and valuable to its differentiation from physiological aging and other dementias.

White matter hyperintensities and cholinergic degeneration as Lewy body disease.

Although basal forebrain (BF) cholinergic degeneration and white matter hyperintensities (WMHs) are important in neurodegeneration in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), their relationships with dopaminergic degeneration and clinical manifestations remain unclear. A total of 407 patients with cognitive impairment meeting the diagnostic criteria for AD, DLB, or both (AD+DLB) were assessed. All participants underwent 3T MRI, dopamine transporter (DAT) positron emission tomography, neuropsychological tests, and assessments for parkinsonism, cognitive fluctuation, visual hallucination, and rapid eye movement sleep behavior disorder (RBD). General linear and logistic regression models were used to investigate the relationships among BF volume, DAT uptake in the anterior caudate (DAT-AC), WMH volumes in anterior, posterior, periventricular, and deep regions, and clinical manifestations. DAT-AC was positively associated with BF volume and negatively associated with anterior periventricular WMH volume, but not with deep WMHs. Both deep and periventricular WMHs volumes were associated with hypertension and the number of microbleeds and lacunae. Lower BF volume and DAT-AC were independently associated with increased risk of cognitive fluctuation and visual hallucination, whereas lower DAT-AC was additionally associated with increased risk of RBD and greater parkinsonian severity. Both lower BF volume and DAT-AC were independently associated with widespread cognitive impairment, whereas higher anterior periventricular WMH volume was associated with executive dysfunction. BF cholinergic degeneration and anterior periventricular WMHs are closely associated with dopaminergic degeneration. Anterior periventricular WMHs may represent axonal alterations caused by the interplay between Lewy body-related degeneration and vascular pathologies.

White Matter Hyperintensities and Cholinergic Degeneration as Lewy Body Disease

AbstractBackgroundTo investigate the relationship between basal forebrain (BF) cholinergic activity, dopaminergic degeneration, white matter hyperintensities (WMHs), and their effects on clinical manifestations of Alzheimer’s disease (AD) and Lewy body disease (LBD).MethodA total of 407 subjects who underwent 3‐T MRI, dopamine transporter (DAT) positron emission tomography, neuropsychological tests, and assessments for parkinsonism, cognitive fluctuation (CF), visual hallucination (VH), and rapid eye movement sleep behavior disorder (RBD) were evaluated for probable AD, LBD, or both (AD+LBD). General linear models were used to investigate the relationships between BF volume (BFV), striatal DAT uptake, WMHs, and clinical manifestations after controlling for age, sex, education, vascular factors, and intracranial volume. Quantitative analyses of DAT uptake in the anterior caudate (AC), posterior caudate (PC), anterior putamen (AP), and posterior putamen (PP) and assessment of WHMs in the anterior/posterior periventricular (PWMH‐A/PWMH‐P) and deep regions (DWMH‐A/DWMH‐P) were performed.ResultDAT‐AC was positively associated with BFV. DAT‐AC was negatively associated with PWMH‐A, but not with DWMHs, independent of BFV. Both DWMHs and PWMHs were associated with hypertension and the number of microbleeds and lacunae. Lower BFV and DAT‐AC were independently associated with increased risk of CF and VH, whereas lower DAT‐AC was additionally associated with an increased risk of RBD and higher parkinsonian severity. Lower BFV and DAT‐AC were independently associated with widespread cognitive impairment, whereas higher PWMH‐A was associated with executive dysfunction.ConclusionCholinergic degeneration in the BF and PWMH‐A levels are closely associated with dopaminergic degeneration. PWMH‐A may be a manifestation of axonal alterations caused by the interplay between LB‐related degeneration and vascular pathologies.

Pilot study of Myocardial MIBG Scintigraphy with 123I‐FP‐CIT SPECT in Isolated REM Sleep Behavior Disorder

AbstractBackgroundAutopsy studies in Lewy Body Disease (LBD) indicate that cardiac sympathetic denervation precedes Lewy body pathology and neuronal loss in the brain. Myocardial 123I‐metaiodobenzylguanidine (MIBG) scintigraphy noninvasively assesses postganglionic cardiac sympathetic denervation in LBD and is considered an important biomarker in the international diagnostic criteria of Dementia with Lewy Bodies and Parkinson’s Disease (PD). Despite the internationally recognized importance of MIBG scintigraphy in LBD, its use in neurodegenerative disorders is not FDA approved for this indication and is rarely used in the US for neurological research. We sought to add MIBG scintigraphy to our multimodal imaging research in prodromal LBD. We launched pilot MIBG scintigraphy study in isolated REM Sleep Behavior Disorder (iRBD) individuals, who are typically regarded as representing evolving LBD.MethodWe conducted MIBG scintigraphy and 123I‐FP‐CIT SPECT in seven individuals with iRBD including two RBD with mild cognitive impairment (MCI), one with PD, and one healthy control (mean age of 71.5±8.3). Heart‐to‐mediastinum (H/M) ratio of the MIBG uptake on delayed image (3‐4 hours after Adreview® injection) was calculated with MIM. Cutoff value of 1.68 was used for determining abnormal H/M ratio (Yoshita et al, 2006). Nigrostriatal dopamine transporter uptake was evaluated with DaTQUANT 2.0 software.ResultFour iRBD participants including two RBD with MCI had abnormal MIBG scintigraphy (mean age 73.5±8.6, delayed H/M ratio 1.25±0.29)) and three iRBD participants had a normal scan (mean age 67.8±4.5, delayed H/M ratio 2.57±0.25). Delayed H/M ratio was 1.00 for the PD participant and 2.60 for healthy control participant. Among the four iRBD participants with abnormal MIBG scintigraphy, one participant had 123I‐FP‐CIT SPECT with DaTQUANT putamen z‐score &lt;‐2.0 and three participants had z‐score in the range of ‐1.5 and ‐1.0. All iRBD participants with normal MIBG scintigraphy had normal 123I‐FP‐CIT SPECT with DaTQUANT putamen z‐score &gt;‐1.0.ConclusionMIBG scintigraphy was abnormal in half of this small cohort. Our preliminary data suggests its utility in detecting early signs of evolving LBD. Increasing the number of the MIBG scintigraphy in iRBD participants and controls are planned to determine if MIBG scintigraphy can facilitate early detection of progression for use in clinical trials targeting LBD.

Comparison of the ability of different quantitative indices in 123I-FP-CIT single-photon emission computed tomography to differentiate dopaminergic neurodegenerative disease

PurposeBy imaging dopamine transporter (DAT) uptake in the striatum, 123I-FP-CIT SPECT can differentiate dopaminergic neurodegenerative disease (dNDD) and non-dNDD, which differ in pathophysiology and clinical management. Our aim was to compare and validate the diagnostic abilities of various 123I-FP-CIT SPECT quantitative indices for dNDD.Materials and methodsDistribution volume ratio (DVR) and binding ratio (BR), measures of DAT uptake capacity, were measured by analyzing clinical 123I-FP-CIT SPECT images of 29 patients with dNDD, including dementia with Lewy bodies and Parkinson’s disease, and 18 patients with non-dNDD, using Montreal Neurological Institute space-based anatomical standardization and an atlas template, which utilizes statistical parametric mapping. Additionally, we computed the specific binding ratio (SBR) based on Bolt’s method and the maximum and mean standardized uptake values (SUVmax and SUVmean, respectively).ResultsThe caudate-to-occipital lobe, putamen-to-occipital lobe, and striatum-to-occipital lobe ratios (COR, POR, and SOR, respectively) on DVR and POR and SOR on BR were significantly lower in dNDD than in non-dNDD, with areas under the ROC curve (AUCs) of 0.941–0.960, showing high diagnostic accuracy for dNDD. However, the AUC of COR on BR was 0.839, indicating lower diagnostic performance. SBR had an AUC of 0.921, while SUVmax and SUVmean had AUCs of 0.906 and 0.900, respectively. Although striatal asymmetry on both DVR and BR exhibited AUCs of 0.728 and 0.734 and asymmetry on SBR showed an AUC of 0.757, the ratio-based DAT quantitative indices were superior. There were strong positive correlations of DVR with BR, DVR with SBR or SUVmax, BR with SBR or SUVmax, and SBR with SUVmax.ConclusionCOR, POR, and SOR on DVR and POR and SOR on BR were the most useful DAT quantitative indices. These indices can be compared with SBR and SUV, suggesting that comprehensive evaluation improves the diagnostic accuracy of dNDD.

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 &lt; 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

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.

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

Glymphatic 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). This 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. In 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). DTI-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

Parkinson'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. Data 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. There 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. There is no evidence that antihypertensive drugs can delay PD progression within 2 years.