Visual reading for [18F]Florzolotau Tau PET scans in progressive supranuclear palsy.

PURPOSE: The identification of tau accumulation within living brains holds significant potential in facilitating accurate diagnosis of progressive supranuclear palsy (PSP). While visual assessment is frequently employed, standardized methods for tau positron emission tomography (PET) specifically in PSP are absent. We aimed to develop a visual reading algorithm dedicated to the evaluation of [18F]Florzolotau PET in PSP. METHODS: 148 PSP and 30 healthy volunteers were divided into a development set (for the establishment of the reading rules; n = 89) and a testing set (for the validation of the reading rules; n = 89). For differential diagnosis, 55 α-synucleinopathies were additionally included into the testing set. The visual reading method was established by an experienced assessor (Reader 0) and was then validated by Reader 0 and two additional readers on regional and overall binary manners. A positive binding in both midbrain and globus pallidus/putamen regions was characterized as a PSP-like pattern, whereas any other pattern was classified as non-PSP-like. RESULTS: Reader 1 (94.4%) and Reader 2 (93.8%) showed excellent agreement for the overall binary determination against Reader 0. The regional binary determinations of midbrain and globus pallidus/putamen showed excellent agreement among readers (kappa > 0.80). The overall binary evaluation demonstrated reproducibility of 86.1%, 94.4% and 77.8% for three readers. The visual reading algorithm showed high agreement with regional standardized uptake value ratios and clinical diagnoses. CONCLUSION: Through the application of the suggested visual reading algorithm, [18F]Florzorotau PET imaging demonstrated a robust performance for the imaging diagnosis of PSP.

Incremental value of amyloid PET in a tertiary memory clinic setting in China.

INTRODUCTION: The objective of this study is to investigate the incremental value of amyloid positron emission tomography (Aß-PET) in a tertiary memory clinic setting in China. METHODS: A total of 1073 patients were offered Aß-PET using 18F-florbetapir. The neurologists determined a suspected etiology (Alzheimer's disease [AD] or non-AD) with a percentage estimate of their confidence and medication prescription both before and after receiving the Aß-PET results. RESULTS: After disclosure of the Aß-PET results, etiological diagnoses changed in 19.3% of patients, and diagnostic confidence increased from 69.3% to 85.6%. Amyloid PET results led to a change of treatment plan in 36.5% of patients. Compared to the late-onset group, the early-onset group had a more frequent change in diagnoses and a higher increase in diagnostic confidence. DISCUSSION: Aß-PET has significant impacts on the changes of diagnoses and management in Chinese population. Early-onset cases are more likely to benefit from Aß-PET than late-onset cases. HIGHLIGHTS: Amyloid PET contributes to diagnostic changes and its confidence in Chinese patients. Amyloid PET leads to a change of treatment plans in Chinese patients. Early-onset cases are more likely to benefit from amyloid PET than late-onset cases.

18F-Florzolotau PET imaging captures the distribution patterns and regional vulnerability of tau pathology in progressive supranuclear palsy.

PURPOSE: Human post mortem studies have described the topographical patterns of tau pathology in progressive supranuclear palsy (PSP). Recent advances in tau PET tracers are expected to herald the next era of PSP investigation for early detection of tau pathology in living brains. This study aimed to investigate whether 18F-Florzolotau PET imaging may capture the distribution patterns and regional vulnerability of tau pathology in PSP, and to devise a novel image-based staging system. METHODS: The study cohort consisted of 148 consecutive patients with PSP who had undergone 18F-Florzolotau PET imaging. The PSP rating scale (PSPrs) was used to measure disease severity. Similarities and differences of tau deposition among different clinical phenotypes were examined at the regional and voxel levels. An 18F-Florzolotau pathological staging system was devised according to the scheme originally developed for post mortem data. In light of conditional probabilities for the sequence of events, an 18F-Florzolotau modified staging system by integrating clusters at the regional level was further developed. The ability of 18F-Florzolotau staging systems to reflect disease severity in terms of PSPrs score was assessed by analysis of variance. RESULTS: The distribution patterns of 18F-Florzolotau accumulation in living brains of PSP showed a remarkable similarity to those reported in post mortem studies, with the binding intensity being markedly higher in Richardson's syndrome. Moreover, 18F-Florzolotau PET imaging allowed detecting regional vulnerability and tracking tau accumulation in an earlier fashion compared with post mortem immunostaining. The 18F-Florzolotau staging systems were positively correlated with clinical severity as reflected by PSPrs scores. CONCLUSIONS: 18F-Florzolotau PET imaging can effectively capture the distribution patterns and regional vulnerability of tau pathology in PSP. The 18F-Florzolotau modified staging system holds promise for early tracking of tau deposition in living brains.

18 F-Florzolotau Positron Emission Tomography Imaging of Tau Pathology in the Living Brains of Patients with Corticobasal Syndrome.

BACKGROUND: Recent development in tau-sensitive tracers has sparkled significant interest in tracking tauopathies using positron emission tomography (PET) biomarkers. However, the ability of 18 F-florzolotau PET imaging to topographically characterize tau pathology in corticobasal syndrome (CBS) remains unclear. Further, the question as to whether disease-level differences exist with other neurodegenerative tauopathies is still unanswered. OBJECTIVE: To analyze the topographical patterns of tau pathology in the living brains of patients with CBS using 18 F-florzolotau PET imaging and to examine whether differences with other tauopathies exist. METHODS: 18 F-florzolotau PET imaging was performed in 20 consecutive patients with CBS, 20 cognitively healthy controls (HCs), 20 patients with Alzheimer's disease (AD), and 16 patients with progressive supranuclear palsy-Richardson's syndrome (PSP-RS). Cerebrospinal fluid (CSF) levels of ß-amyloid biomarkers were quantified in all patients with CBS. 18 F-florzolotau uptake was quantitatively assessed using standardized uptake value ratios. RESULTS: Of the 20 patients with CBS, 19 (95%) were negative for CSF biomarkers of amyloid pathology; of them, three had negative 18 F-florzolotau PET findings. Compared with HCs, patients with CBS showed increased 18 F-florzolotau signals in both cortical and subcortical regions. In addition, patients with CBS were characterized by higher tracer retentions in subcortical regions compared with those with AD and showed a trend toward higher signals in cortical areas compared with PSP-RS. An asymmetric pattern of 18 F-florzolotau uptake was associated with an asymmetry of motor severity in patients with CBS. CONCLUSIONS: In vivo 18 F-florzolotau PET imaging holds promise for distinguishing CBS in the spectrum of neurodegenerative tauopathies. © 2023 International Parkinson and Movement Disorder Society.

18 F-Florzolotau Tau Positron Emission Tomography Imaging in Patients with Multiple System Atrophy-Parkinsonian Subtype.

BACKGROUND: Anecdotal evidence suggests that patients diagnosed with the parkinsonian subtype of multiple system atrophy (MSA-P) may show uptake of the second-generation tau positron emission tomography (PET) tracer 18 F-Florzolotau (previously known as 18 F-APN-1607) in the putamen. OBJECTIVES: This study systematically investigated the localization and magnitude of 18 F-Florzolotau uptake in a relatively large cohort of patients with MSA-P. METHODS: 18 F-Florzolotau PET imaging was performed in 31 patients with MSA-P, 24 patients with Parkinson's disease (PD), and 20 age-matched healthy controls. 18 F-Florzolotau signal in the striatum was analyzed by visual inspection and classified as either positive or negative. Regional 18 F-Florzolotau binding was also expressed as standardized uptake value ratio (SUVR) to assess whether it was associated with core symptoms of MSA-P after adjustment for potential confounders. RESULTS: By visual inspection and semiquantitative SUVR comparisons, patients with MSA-P showed elevated 18 F-Florzolotau uptake in the putamen, globus pallidus, and dentate-a finding that was not observed in PD. This increased signal was significantly associated with the core symptoms of MSA-P. In addition, patients with MSA-P with cerebellar ataxia showed an elevated 18 F-Florzolotau uptake in the cerebellar dentate. CONCLUSIONS: 18 F-Florzolotau tau PET imaging findings may reflect the clinical severity of MSA-P and can potentially discriminate between this condition and PD. © 2022 International Parkinson and Movement Disorder Society.

Clinical characteristics of cognitive impairment in patients with Parkinson's disease and its related pattern in 18 F-FDG PET imaging.

This study aimed to characterize the clinical features and the related cerebral glucose metabolism pattern of cognitive impairments in Parkinson's disease (PD) with positron emission tomography (PET) imaging. We recruited 168 PD patients and 100 age-matched healthy controls of similar education and gender distribution. All of those enrolled underwent clinical assessment including the unified Parkinson's disease rating scale motor score, Hoehn and Yahr scale, and comprehensive neuropsychological tests including domains of executive function, attention, memory, visuospatial function, and language. Demographics and the results of cognitive measures were compared between patients and healthy controls. Cognition status was classified as PD patients with dementia (PD-D), PD patients with mild cognitive impairment (PD-MCI), or PD patients with normal cognition (PD-NC). In 53 PD patients who underwent 18 F-fluorodeoxyglucose (18 F-FDG) PET imaging, correlations between Z-score values of the different cognitive domains and cerebral 18 F-FDG uptake were assessed using statistical parametric mapping (SPM8) corrected for age and motor severity. A total of 23.2% of PD patients were PD-MCI and 8.9% were PD-D. In the group of PD-MCI, 96.3% showed multiple-domain deficits, with executive function and attention impairment most predominantly involved. All the cognitive domain scores with the exception of language correlated with 18 F-FDG metabolisms, primarily in posterior temporo-parieto-occipital association cortical areas. This study found that cognitive impairment in PD particularly encompasses frontal/executive deficits. Posterior cortical areas, containing multiple neurotransmitters and neural circuits, may play an important role in the pathogenesis of cognitive impairment in PD.

Dopaminergic Dysfunction and Glucose Metabolism Characteristics in Parkin-Induced Early-Onset Parkinson's Disease Compared to Genetically Undetermined Early-Onset Parkinson's Disease.

While early-onset Parkinson's disease (EOPD) caused by mutations in the parkin gene (PRKN) tends to have a relatively benign course compared to genetically undetermined (GU)-EOPD, the exact underlying mechanisms remain elusive. We aimed to search for the differences between PRKN-EOPD and GU-EOPD by dopamine transporter (DAT) and glucose metabolism positron-emission-tomography (PET) imaging. Twelve patients with PRKN-EOPD and 16 with GU-EOPD who accepted both 11C-2b-carbomethoxy-3b-(4-trimethylstannylphenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose PET were enrolled. The 11C-CFT uptake was analyzed on both regional and voxel levels, whereas glucose metabolism was assessed in a voxel-wise fashion. Correlations between DAT and glucose metabolism imaging, DAT imaging and clinical severity, as well as glucose metabolism imaging and clinical severity were explored. Both clinical symptoms and DAT-binding patterns in the posterior putamen were highly symmetrical in patients with PRKN-EOPD, and dopaminergic dysfunction in the ipsilateral putamen was severer in patients with PRKN-EOPD than GU-EOPD. Meanwhile, the DAT binding was associated with the severity of motor dysfunction in  patients with GU-EOPD only. Patients with PRKN-EOPD showed increased glucose metabolism in the contralateral medial frontal gyrus (supplementary motor area (SMA)), contralateral substantia nigra, contralateral thalamus, and contralateral cerebellum. Notably, glucose metabolic activity in the contralateral medial frontal gyrus was inversely associated with regional DAT binding in the bilateral putamen. Patients with PRKN-EOPD showed enhanced metabolic connectivity within the bilateral putamen, ipsilateral paracentral and precentral lobules, and the ipsilateral SMA. Collectively, compared to GU-EOPD, PRKN-EOPD is characterized by symmetrical, more severe dopaminergic dysfunction and relative increased glucose metabolism. Meanwhile, SMA with elevated glucose metabolism and enhanced connectivity may act as compensatory mechanisms in PRKN-EOPD. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-022-00077-8.

Autosomal dominant Parkinson's disease caused by the recently identified LRRK2 N1437D mutation in a Chinese family: Clinical features, imaging findings, and functional impact.

INTRODUCTION: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of autosomal dominantly inherited Parkinson's disease (PD). Recently, a novel pathogenic variant (N1437D; c.4309A > G; NM_98578) in the LRRK2 gene has been identified in three Chinese families with PD. In this study, we describe a Chinese family with autosomal dominant PD that segregated with the N1437D mutation. A detailed clinical and neuroimaging characterization of the affected family members is reported. We also sought to investigate the functional mechanisms by which the detected mutation could cause PD. METHODS: We characterized the clinical and imaging phenotype of a Chinese pedigree with autosomal dominant PD. We searched for a disease-causing mutation by targeted sequencing and multiple ligation-dependent probe amplification. The functional impact of the mutation was investigated in terms of LRRK2 kinase activity, guanosine triphosphate (GTP) binding, and guanosine triphosphatase (GTPase) activity. RESULTS: The disease was found to co-segregate with the LRRK2 N1437D mutation. Patients in the pedigree exhibited typical parkinsonism (age at onset: 54.0 ± 5.9 years). One affected family member - who had evidence of abnormal tau accumulation in the occipital lobe on tau PET imaging - developed PD dementia at follow-up. The mutation markedly increased LRRK2 kinase activity and promoted GTP binding, without affecting GTPase activity. CONCLUSIONS: This study describes the functional impact of a recently identified LRRK2 mutation, N1437D, that causes autosomal dominant PD in the Chinese population. Further research is necessary to investigate the contribution of this mutation to PD in multiple Asian populations.

Cerebral Metabolism Related to Cognitive Impairments in Multiple System Atrophy.

Objective: We aimed to characterize the cognitive profiles in multiple system atrophy (MSA) and explore the cerebral metabolism related to the cognitive decline in MSA using 18F-fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET). Methods: In this study, 105 MSA patients were included for cognitive assessment and 84 of them were enrolled for 18F-FDG PET analysis. The comprehensive neuropsychological tests covered five main domains including execution, attention, memory, language, and visuospatial function. The cognitive statuses were classified to MSA with normal cognition (MSA-NC) and MSA with cognitive impairment (MSA-CI), including dementia (MSA-D), and mild cognitive impairment (MSA-MCI). With 18F-FDG PET imaging, the cerebral metabolism differences among different cognitive statuses were analyzed using statistical parametric mapping and post-hoc analysis. Results: Among 84 MSA patients, 52 patients were found with MSA-CI, including 36 patients as MSA-MCI and 16 patients as MSA-D. In detail, the cognitive impairments were observed in all the five domains, primarily in attention, executive function and memory. In 18F-FDG PET imaging, MSA-D and MSA-MCI patients exhibited hypometabolism in left middle and superior frontal lobe compared with MSA-NC (p < 0.001). The normalized regional cerebral metabolic rate of glucose (rCMRglc) in left middle frontal lobe showed relative accuracy in discriminating MSA-CI and MSA-NC [areas under the curve (AUC) = 0.750; 95%CI = 0.6391-0.8609]. Conclusions: Cognitive impairments were not rare in MSA, and the hypometabolism in frontal lobe may contribute to such impairments.

Brain Metabolisms Involved in Self-Reported Quality of Mobility in Parkinson's Disease.

BACKGROUND: Objective motor ratings and subjective motor complaints are both widely used in Parkinson's disease (PD). However, the objective basis to the self-perceived mobility quality is still not well elucidated. PURPOSES: We aimed to figure out the relevancy between the UPDRS motor scores and PDQ39 mobility sub-scores, and further explore whether physician-assessed motor dysfunctions and patients-reported mobility deficits have some shared mechanisms. METHODS: 49 patients with PD who completed the PDQ39 scale were retrospectively included. The relevancy between mobility quality and UPDRS scores was assessed, as well as the related presynaptic dopaminergic binding (11C-CFT) and glucose metabolism (18F-FDG) in this dual-tracer PET imaging study. RESULTS: Modest correlation was found between UPDRS motor score and the PDQ39 mobility sub-score (r = 0.440, p = 0.002). No correlation was found between PDQ39 mobility SI and the dopaminergic lesions in putamen; however, the strict correlation was found with the UPDRS motor scores. In terms of global PD related pattern (PDRP) scores, the two motor scores both correlated strictly. In the further regional metabolism exploration, cerebellum correlated positively with PDQ39 mobility sub-scores, and the frontal and parietal regions mainly correlated negatively with the motor quality scores. CONCLUSION: UPDRS motor scores and PDQ39 mobility scores were only modestly correlated. The mechanisms involved under mobility quality were beyond dopaminergic deficiency, including motor related cerebellum hyper-metabolism and non-motor related frontal hypo-metabolism. Conclusively, the self-reported mobility experience may have the neurophysiological basis related to both motor and non-motor manifestations in PD.

Forniceal deep brain stimulation in severe Alzheimer's disease: A case report.

BACKGROUND: Forniceal deep brain stimulation (DBS) has been proposed as an alternative treatment for Alzheimer's disease (AD). Previous studies on mild to moderate AD patients demonstrated improvements in cognitive functions brought about by forniceal DBS. Here, we report our longitudinal findings in one severe AD patient for whom the activities of daily living (ADL) rather than cognitive function significantly improved after 3 mo of continuous stimulation. CASE SUMMARY: In 2011, a 62-year-old Chinese male with no previous history of brain injury or other neuropsychological diseases and no family history of dementia developed early symptoms of memory decline and cognitive impairment. Five years later, the symptoms had increased to the extent that they affected his daily living. He lost the ability to work as a businessman and to take care of himself. The patient was given a clinical diagnosis of probable AD and was prescribed donepezil and subsequently memantine, but no improvement in symptoms was observed. The patient then received DBS surgery. After 3 mo of continuous stimulation, the patient's ADL score decreased from 65 points to 47 points, indicating the quality of the patient's daily living improved distinctly. Other scores remained unchanged, suggesting no significant improvement in cognitive function. A follow-up positron emission tomography scan demonstrated perceivable increased glucose metabolism in the classical AD-related brain regions. CONCLUSION: Based on this case we hypothesize that forniceal DBS may improve ADL through elevating regional glucose metabolism in the brain.

Fasudil Promotes α-Synuclein Clearance in an AAV-Mediated α-Synuclein Rat Model of Parkinson's Disease by Autophagy Activation.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder, but the disease-modifying therapies focusing on the core pathological changes are still unavailable. Rho-associated protein kinase (ROCK) has been suggested as a promising target for developing neuroprotective therapies in PD. OBJECTIVE: We aimed to explore the promotion of α-synuclein (α-syn) clearance in a rat model. METHODS: In a rat model induced by unilateral injection of adeno-associated virus of serotype 9 (AAV9) expressing A53T α-syn (AAV9-A53T-α-syn) into the right substantia nigra, we aimed to investigate whether Fasudil could promote α-syn clearance and thereby attenuate motor impairments and dopaminergic deficits. RESULTS: In our study, treatment with Fasudil (5 mg/kg rat weight/day) for 8 weeks significantly improved the motor deficits in the Cylinder and Rotarod tests. In the in vivo positron emission tomography imaging with the ligand 18F-dihydrotetrabenazine, Fasudil significantly enhanced the dopaminergic imaging in the injected striatum of the rat model (p < 0.05 vs. vehicle group, p < 0.01 vs. left striatum in Fasudil group). The following mechanistic study confirmed that Fasudil could promote the autophagic clearance of α-syn by Becline 1 and Akt/mTOR pathways. CONCLUSION: Our study suggested that Fasudil, the ROCK2 inhibitor, could attenuate the anatomical and behavioral lesions in the Parkinsonian rat model by autophagy activation. Our results identify Fasudil as a drug with high translational potential as disease-modifying treatment for PD and other synucleinopathies.

Assessing gray matter volume in patients with idiopathic rapid eye movement sleep behavior disorder.

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is often a precursor to neurodegenerative disease. However, voxel-based morphological studies evaluating structural abnormalities in the brains of iRBD patients are relatively rare. This study aimed to explore cerebral structural alterations using magnetic resonance imaging and to determine their association with clinical parameters in iRBD patients. Brain structural T1-weighted MRI scans were acquired from 19 polysomnogram-confirmed iRBD patients (male:female 16:3; mean age 66.6 ± 7.0 years) and 20 age-matched healthy controls (male:female 5:15; mean age 63.7 ± 5.9 years). Gray matter volume (GMV) data were analyzed based on Statistical Parametric Mapping 8, using a voxel-based morphometry method and two-sample t-test and multiple regression analysis. Compared with controls, iRBD patients had increased GMV in the middle temporal gyrus and cerebellar posterior lobe, but decreased GMV in the Rolandic operculum, postcentral gyrus, insular lobe, cingulate gyrus, precuneus, rectus gyrus, and superior frontal gyrus. iRBD duration was positively correlated with GMV in the precuneus, cuneus, superior parietal gyrus, postcentral gyrus, posterior cingulate gyrus, hippocampus, lingual gyrus, middle occipital gyrus, middle temporal gyrus, and cerebellum posterior lobe. Furthermore, phasic chin electromyographic activity was positively correlated with GMV in the hippocampus, precuneus, fusiform gyrus, precentral gyrus, superior frontal gyrus, cuneus, inferior parietal lobule, angular gyrus, superior parietal gyrus, paracentral lobule, and cerebellar posterior lobe. There were no significant negative correlations of brain GMV with disease duration or electromyographic activity in iRBD patients. These findings expand the spectrum of known gray matter modifications in iRBD patients and provide evidence of a correlation between brain dysfunction and clinical manifestations in such patients. The protocol was approved by the Ethics Committee of Huashan Hospital (approval No. KY2013-336) on January 6, 2014. This trial was registered in the ISRCTN registry (ISRCTN18238599).

Use of radiomic features and support vector machine to distinguish Parkinson's disease cases from normal controls.

BACKGROUND: Parkinson's disease (PD) is an irreversible neurodegenerative disease. The diagnosis of PD based on neuroimaging is usually with low-level or deep learning features, which results in difficulties in achieving precision classification or interpreting the clinical significance. Herein, we aimed to extract high-order features by using radiomics approach and achieve acceptable diagnosis accuracy in PD. METHODS: In this retrospective multicohort study, we collected 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) images and clinical scale [the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn & Yahr scale (H&Y)] from two cohorts. One cohort from Huashan Hospital had 91 normal controls (NC) and 91 PD patients (UPDRS: 22.7±11.7, H&Y: 1.8±0.8), and the other cohort from Wuxi 904 Hospital had 26 NC and 22 PD patients (UPDRS: 20.9±11.6, H&Y: 1.7±0.9). The Huashan cohort was used as the training and test sets by 5-fold cross-validation and the Wuxi cohort was used as another separate test set. After identifying regions of interests (ROIs) based on the atlas-based method, radiomic features were extracted and selected by using autocorrelation and fisher score algorithm. A support vector machine (SVM) was trained to classify PD and NC based on selected radiomic features. In the comparative experiment, we compared our method with the traditional voxel values method. To guarantee the robustness, above processes were repeated in 500 times. RESULTS: Twenty-six brain ROIs were identified. Six thousand one hundred and ten radiomic features were extracted in total. Among them 30 features were remained after feature selection. The accuracies of the proposed method achieved 90.97%±4.66% and 88.08%±5.27% in Huashan and Wuxi test sets, respectively. CONCLUSIONS: This study showed that radiomic features and SVM could be used to distinguish between PD and NC based on 18F-FDG PET images.

Preserved caudate function in young-onset patients with Parkinson's disease: a dual-tracer PET imaging study.

Parkinson's disease (PD) is a highly heterogeneous clinical entity. Patients with young-onset PD (YOPD) show some characteristic manifestations to late-onset PD (LOPD). The current study aimed to investigate the cerebral dopaminergic and metabolic characteristics in YOPD with positron emission tomography (PET) imaging. In our study, 103 subjects (42 YOPD and 61 LOPD patients) accepted both 11C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) cerebral PET imaging. Sixty-two patients out of 103 patients in our study completed the cognition tests. In this limited subsection, YOPD patients performed better in cognitive functioning than LOPD patients of similar disease duration. In 11C-CFT imaging, dopamine transporter binding in caudate was relatively spared in YOPD compared with lesions in putamen. In 18F-FDG PET, YOPD patients showed increased metabolism in basal ganglia relative to the healthy controls. When compared with LOPD patients, YOPD patients exhibited hypermetabolism in caudate and hypometabolism in putamen. Furthermore, the regional metabolic values in caudate correlated positively and moderately with the dopaminergic binding deficiency in caudate. The findings of this imaging study might offer new perspectives in understanding the characteristic manifestations in YOPD in light of better-preserved cognition function.

Clinical, Dopaminergic, and Metabolic Correlations in Parkinson Disease: A Dual-Tracer PET Study.

PURPOSE: Neuroimaging indicators of Parkinson disease have been developed and applied in clinical practices. Dopaminergic imaging reflects nigrostriatal dopaminergic dysfunction, and metabolic network imaging offers disease-related metabolic changes at a system level. We aimed to elucidate the association between Parkinsonian symptoms and neuroimaging, and interactions between different imaging techniques. METHODS: We conducted a dual-tracer PET study for the combined assessments of dopaminergic binding (C-CFT) and glucose metabolism (F-FDG) in 103 participants with Parkinson disease (65 male and 38 female subjects). The detailed clinical rating scores were systematically collected in all members. The interactions among dopaminergic bindings, metabolic changes, and clinical manifestations were evaluated at voxel, regional, and network levels. RESULTS: Striatal DAT binding correlated with akinesia-rigidity (P < 0.001) but not with tremor; the metabolic PET imaging, nonspecific to the dopaminergic dysfunction, disclosed a set of brain regions correlating with the cardinal symptoms, including tremor. In addition, the unilateral symptom correlated with the contralateral nigrostriatal dopamine loss, but with bilateral metabolic changes, suggesting their differences in the application of disease-related mechanistic studies. Further imaging-imaging correlation study revealed that dopaminergic dysfunction correlated with widely distributed metabolic changes in Parkinson disease, and the modest correlations supported the findings on the clinical-imaging correlation. CONCLUSIONS: In this dual-tracer PET study, we demonstrated the robust interactions among dopaminergic dysfunction, metabolic brain changes and clinical manifestations at voxel, regional, and network levels. Our findings might promote the understanding in the proper application of dopaminergic and metabolic PET imaging in Parkinson disease and offer more evidence in support of Parkinsonian pathophysiological mechanisms.

Transition-Metal-Free Deacylative Cleavage of Unstrained C(sp(3))-C(sp(2)) Bonds: Cyanide-Free Access to Aryl and Aliphatic Nitriles from Ketones and Aldehydes.

A transition-metal-free deacylative C(sp(3))-C(sp(2)) bond cleavage for the synthetically practical oxidative amination of ketones and aldehydes to nitriles is first described, using cheap and commercially abundant NaNO2 as the oxidant and the nitrogen source. Various nitriles bearing aryl, heteroaryl, alkyl, and alkenyl groups could be smoothly obtained from ketones and aldehydes in high yields, avoiding highly toxic cyanides or transition metals.

Analysis of glucose metabolism of (18)F-FDG in major depression patients using PET imaging: Correlation of salivary cortisol and α-amylase.

Current diagnosis of Major depressive disorder (MDD) depends on its clinical symptoms, not on the results of any laboratory examinations. Establishing biological markers for diagnosis of MDD is one of the most important problems to be solved in psychiatry practice. MDD patients (n=8) and a healthy control group (n=8) were recruited in this study. Hamilton Depression Rating Scale (HAM-D) assessments were completed and saliva samples were collected for assessments of salivary cortisol and salivary α-amylase (sAA). PET examination was performed. Salivary cortisol and sAA in the MDD patients group were significantly higher than the healthy control group (P<0.001). MDD patients showed lower glucose metabolism of 18F-FDG in Cingulate Gyrus (BA24), Superior Frontal Gyrus (BA6), Rectal Gyrus (BA11) and Orbital Gyrus (BA11/47) compared with the healthy control group. The severity of depression, salivary cortisol and sAA correlated negatively with regional glucose metabolism in Cingulate Gyrus (BA 24), Superior Frontal Gyrus (BA 6), Rectal Gyrus (BA 11) and Orbital Gyrus (BA 11/47). The combination of salivary cortisol, sAA, superior frontal gyrus and rectal gyrus was the potential predictor of depression for MDD patients (ΔR(2)=0.981, p<0.001). The present study showed that, MDD patients group showed higher salivary cortisol, sAA levels and lower glucose metabolism of (18)F-FDG in several brain areas compared with the healthy control group. The combination of salivary cortisol, sAA, glucose metabolism of (18)F-FDG of superior frontal gyrus and rectal gyrus may serve as a simple clinical tool for the early diagnosis of MDD.

Onset-related subtypes of Parkinson's disease differ in the patterns of striatal dopaminergic dysfunction: A positron emission tomography study.

PURPOSE: The young-onset subtype of Parkinson's disease (YOPD) differs from the late-onset subtype (LOPD) in drug responsiveness, incidence of motor complications, and prognosis. The pathophysiology underlying these differences remains largely unknown. This study investigated whether the two subtypes differ in the pattern of dysfunction in striatal (caudate and putamen) dopaminergic system and if the dopamine transporter (DAT) imaging patterns are associated with the clinical features of corresponding PD subtype. METHODS: We assessed the spatial pattern of striatal dopaminergic dysfunction in 40 YOPD and 47 LOPD with early to mid-stage PD with DAT imaging by positron emission tomography. Two sub-regional parameters (caudate/putamen ratio and asymmetry index) were calculated to measure the spatial pattern of striatal dopaminergic dysfunction. RESULTS: The caudate/anterior putamen ratios were significantly higher in YOPD than that in the LOPD (P = 0.03 contralateral to the most affected side of the body and P = 0.004 ipsilateral), which was supported by significantly inverse correlations between age of onset and caudate/anterior putamen ratios (r = -0.428, P < 0.001 for the contralateral and r = -0.576, P < 0.001 for the ipsilateral). Sub-regional DAT binding in caudate ipsilateral to affected limbs was significantly correlated with age, while DAT bindings in putamen were significantly inversely correlated with disease duration and UPDRS motor scores. CONCLUSION: The YOPD subtype suffers from an uneven pattern of dopaminergic dysfunction: more sparing of the caudate compared with the putamen, while the LOPD patients is with a relatively uniform pattern.