Yuhu Zhang

The putaminal abnormalities on 3.0T magnetic resonance imaging: can they separate parkinsonism-predominant multiple system atrophy from Parkinson's disease?

Background The putaminal abnormalities detected on 1.5u2009T magnetic resonance imaging (MRI), such as putaminal atrophy, slit-like hyperintense rim, and hypointensity in the putamen on T2-weighted (T2W) imaging are important signs on differentiating multiple system atrophy with parkinsonism (MSA-P) from Parkinsons disease (PD). However, the putaminal abnormalities may have different manifestations on 3.0u2009T from those on 1.5 T. Purpose To investigate the diagnostic value of putaminal abnormalities on 3.0u2009T MRI for differentiating MSA-P from PD. Material and Methods The study included a MSA-P group (9 men, 9 women), a PD group (12 men, 14 women), and a control group (11 men, 13 women). All subjects were examined with 3.0u2009T MRI using the conventional protocol. Putaminal atrophy, T2-hypointensity in the dorsolateral putamenat, and a slit-like hyperintense rim on the lateral putamen were evaluated in each subject. Results There were no significant differences in the slit-like hyperintense rim (Pu2009=u20090.782) or T2-hypointensity in the dorsolateral putamen (Pu2009=u20090.338) among the three groups. Bilateral putaminal atrophy was found in 44.4% (8 of 18) of the MSA-P patients, in only 7.7% (2 of 26) of the PD patients, and in none of the controls. The proportion of subjects with putaminal atrophy was significantly higher in the MAS-P group (Pu2009=u20090.008) and control group (Pu2009<u20090.001). The specificity and sensitivity of putaminal atrophy for distinguishing MSA-P from PD was 92.3% and 44.4%, respectively. Conclusion The signal changes in the putamen on T2W imaging on 3.0u2009T MRI, including slit-like hyperintense rim and putaminal hypointensity, are not specific signs for MSA-P. Putaminal atrophy is highly specific for differentiating MSA-P from PD and healthy controls, but its insufficient sensitivity limits its diagnostic value.

Discriminative Analysis of Parkinson’s Disease Based on Whole-Brain Functional Connectivity

Recently, there has been an increasing emphasis on applications of pattern recognition and neuroimaging techniques in the effective and accurate diagnosis of psychiatric or neurological disorders. In the present study, we investigated the whole-brain resting-state functional connectivity patterns of Parkinsons disease (PD), which are expected to provide additional information for the clinical diagnosis and treatment of this disease. First, we computed the functional connectivity between each pair of 116 regions of interest derived from a prior atlas. The most discriminative features based on Kendall tau correlation coefficient were then selected. A support vector machine classifier was employed to classify 21 PD patients with 26 demographically matched healthy controls. This method achieved a classification accuracy of 93.62% using leave-one-out cross-validation, with a sensitivity of 90.47% and a specificity of 96.15%. The majority of the most discriminative functional connections were located within or across the default mode, cingulo-opercular and frontal-parietal networks and the cerebellum. These disease-related resting-state network alterations might play important roles in the pathophysiology of this disease. Our results suggest that analyses of whole-brain resting-state functional connectivity patterns have the potential to improve the clinical diagnosis and treatment evaluation of PD.

Altered Resting-State Functional Connectivity of the Striatum in Parkinson's Disease after Levodopa Administration.

Background Despite improvement in motor symptoms, the effect of dopaminergic medications on cognition in patients with Parkinson’s disease (PD) is less clear. The purpose of this study was to reveal levodopa-induced acute changes in the functional connectivity of the striatum in patients with PD compared with matched untreated patients and healthy volunteers. Methods Twenty-two patients with PD underwent functional magnetic resonance imaging both ON and OFF dopamine-replacement therapy on two consecutive days. Twenty-eight normal aging volunteers also did them without taking in levodopa. Three caudate seeds and two putamen seeds were selected to calculate functional connectivity intensity. Results Motor symptoms measured by UPDRS were significantly worse in PD OFF than PD ON. Decreased functional connectivity in PD OFF compared to controls was detected in the following seed regions: dorsal caudate, ventral putamen and dorsal putamen. Increases in connectivity in PD ON compared to controls were found in the primary and supplementary motor areas and the associative prefrontal and parietal regions, while decreases in anterior cingulate, ventromedial prefrontal cortex, and parahippocampal gyrus. For the ventral striatal seeds, decreased connectivity in PD ON compared to PD OFF was found in the ventromedial prefrontal and orbitofrontal regions, dorsolateral prefrontal regions. For the dorsal striatal seeds, increased connectivity in PD ON compared to PD OFF was observed in the primary and secondary motor areas. Conclusion Our results suggest that levodopa significantly changes the motor and cognitive networks of the cortico-striatal pathways. This knowledge will lead clinicians to survey a broader range of symptoms in determining optimal therapy.

MCP-1 and CCR2 gene polymorphisms in Parkinson’s disease in a Han Chinese cohort

Monocyte chemoattractant protein-1 (MCP-1) and its receptor CC chemokine receptor-2 (CCR2) play important roles in neuroinflammation and they have been shown to be involved in Parkinson’s disease (PD) pathogenesis. In addition, several studies have suggested a role for the MCP-1 and CCR2 genotypes in cognitive impairment and depression, which are common non-motor symptoms in PD patients. In this study, a cohort of 521 PD patients and 556 cases of healthy controls were recruited to investigate the association between the MCP-1 2518A/G (rs1064211) and CCR2 V64I (rs1799864) gene polymorphisms and PD risk in the Chinese population. We also analyze the influence of these genotypes on the cognitive function and depression in PD patients by comparing Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC), Wechsler Memory Scale-Chinese Revision (WMS-RC) and Hamilton Depression Rating Scale (HAMD) ratings in 217 PD patients. Our results showed no significant differences in the genotype frequency between the PD group and the control group (Pxa0>xa00.05). In addition, we also failed to find an influence of the MCP-1 and CCR2 genotypes on MMSE scores, MoCA scores, WAIS-RC scores, WMS-RC scores and HAMD scores in PD patients (Pxa0>xa00.05). The MCP-1 and CCR2 gene polymorphisms may not be genetic risk factors for PD in the Han Chinese population, and they do not appear to influence cognitive function and depression in PD patients.

RIT2 polymorphism is associated with Parkinson's disease in a Han Chinese population.

Recently, a meta-analysis including 5 large genome-wide association studies has identified rs12456492 variant of RIT2 gene as a novel risk locus for Parkinsons disease (PD) in Caucasian populations. However, the association between RIT2 polymorphism and PD risk has not been positively replicated in Asian population yet. We detected the genotypes of rs12456492 in 524 PD patients and 521 control subjects from a Han Chinese population. The allele and genotype distribution of rs12456492 variant were significantly different between PD patients and controls (allele p = 0.001, genotype p = 0.002). Logistic regression analysis showed that the G-carrying genotype (AG + GG) individuals exhibited a nearly 1.4-fold increased risk for PD compared with the AA genotype carriers (OR = 1.390; 95% confidence interval = 1.079-1.791; p = 0.011). Our data support that the carriage of G allele of rs12456492 variant of RIT2 gene significantly increases the risk for PD in Han Chinese population, suggesting a potential role of RIT2 in the etiology of PD.

Sex differences in cognition among Chinese people with Parkinson’s disease

To investigate sex differences in cognitive function in Parkinsons disease patients, a cohort of 172 male patients and 139 female patients were recruited for this study. Their demographic and clinical features, including age, disease duration, education level, Unified Parkinsons Disease Rating Scale-III, Hoehn-Yahr Scale, activities of daily living, Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale score were recorded. The Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC) and Wechsler Memory Scale-Chinese Revision (WMS-RC) scores were compared to distinguish the cognitive properties between the two groups. The MMSE values did not show a significant difference between the groups. However, the MoCA scores of male patients were significantly higher than those of female patients (adjusted p<0.05). The male group demonstrated better performances with respect to visuospatial function, naming and abstraction (adjusted p<0.05). The WAIS-RC data showed that female patients had lower scores in information, vocabulary, picture completion, block design and picture arrangement (adjusted p<0.05), and the WMS-RC data showed that 100-1 and cumulative addition abilities were significantly weaker in females than males (adjusted p<0.05). Cognitive disturbances were more prevalent and severe in women among Chinese Parkinsons disease patients.

Diffusion Kurtosis Imaging of Substantia Nigra Is a Sensitive Method for Early Diagnosis and Disease Evaluation in Parkinson's Disease

Background. To diagnose Parkinson disease (PD) in an early stage and accurately evaluate severity, it is important to develop a sensitive method for detecting structural changes in the substantia nigra (SN). Method. Seventy-two untreated patients with early PD and 72 healthy controls underwent diffusion tensor and diffusion kurtosis imaging. Regions of interest were drawn in the rostral, middle, and caudal SN by two blinded and independent raters. Mean kurtosis (MK) and fractional anisotropy in the SN were compared between the groups. Receiver operating characteristic (ROC) and Spearman correlation analyses were used to compare the diagnostic accuracy and correlate imaging findings with Hoehn-Yahr (H-Y) staging and part III of the Unified Parkinsons Disease Rating Scale (UPDRS-III). Result. MK in the SN was increased significantly in PD patients compared with healthy controls. The area under the ROC curve was 0.976 for MK in the SN (sensitivity, 0.944; specificity, 0.917). MK in the SN had a positive correlation with H-Y staging and UPDRS-III scores. Conclusion. Diffusion kurtosis imaging is a sensitive method for PD diagnosis and severity evaluation. MK in the SN is a potential biomarker for imaging studies of early PD that can be widely used in clinic.

Changes of brain structure in Parkinson’s disease patients with mild cognitive impairment analyzed via VBM technology

OBJECTIVEnTo analyze changes in cerebral grey matter volume and white matter density in non-dementia Parkinsons disease patients using voxel-based morphometry (VBM) technology; to investigate features of brain structure changes in Parkinsons disease patients with mild cognitive impairment (PD-MCI), and reveal their intrinsic pathological changes.nnnMETHODSnBased on the diagnostic criteria of PD-MCI, 23 PD-MCI patients, 23 Parkinsons disease patients with normal cognition (PD-NC), and 21 age- and gender-matched healthy people were recruited for the study. Scans were performed on all subjects on a 3.0T MR scanner to obtain brain structural magnetic resonance images. Images were preprocessed using the VBM8 tool from SPM8 software package on the Matlab R2008a platform, and data were then analyzed using the SPM statistical software package to compare the differences of grey matter volume and white matter density between groups, and to evaluate the brain structural changes corresponding to the overall cognitive function.nnnRESULTSnCompared to the control group, the PD-NC group suffered from grey matter atrophy, mainly found in the prefrontal lobe, limbic lobe and left temporal gyrus. The PD-MCI group suffered from grey matter atrophy found in the frontal lobe, limbic lobe, basal ganglia and cerebellum. Compared to the PD-NC group, the PD-MCI group suffered from grey matter atrophy found in the left-side middle temporal gyrus, inferior temporal gyrus and frontal lobe. The grey matter regions correlated with MMSE score (mainly memory related) including the right cingulate gyrus and the limbic lobe. The grey matter regions correlated with MoCA score (mainly non-memory related) including the frontal lobe, basal ganglia, parahippocampal gyrus, occipital lobe and the cerebellum. Additionally, overall cognitive function in non-dementia PD was mainly located in the frontal and limbic system, and was dominated by subcortical atrophy.nnnCONCLUSIONnStructural changes in PD-MCI patients are associated with overall cognitive function, and the atrophic areas are mainly located in the frontal and limbic system, and are dominated by subcortical atrophy. Moreover, atrophy of limbic lobes is associated with impaired memory, whereas frontal lobe atrophy is associated with executive dysfunction. In addition, the subtle brain structure of the PD early cognitive impairment stage and PD-MCI stage can be detected via VBM technology, and thus, local brain atrophy may be a neuroimaging marker for the early diagnosis of PD-MCI.

Catechol-O-methyltransferase Val158Met polymorphism influences prefrontal executive function in early Parkinson's disease

OBJECTIVEnThe catechol-O-methyltransferase (COMT) Val158Met polymorphism has been proposed to be associated with increased risk of Parkinsons disease (PD) and have a specific impact on dopamine-mediated prefrontal executive function in an inverted-U curve manner. We explored the influence of this genetic polymorphism on prefrontal executive function in a well-established Chinese cohort of early PD patients with no current or past history of motor fluctuations or dyskinesias.nnnMETHODSnCognitive functions were assessed in 250 patients with early PD using Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC) and Wechsler Memory Scale-Chinese Revision (WMS-RC). These patients and 300 healthy controls were subsequently genotyped for the COMT gene Val158Met polymorphism. We employed analysis of covariance (ANCOVA) and a stratified analysis to determine the associations between the COMT Val158Met genotype and cognitive functions.nnnRESULTSnThe COMT Val158Met allele frequency and genotype distributions showed no statistically significant differences between PD patients and controls. However, patients with met/met genotype performed significantly worse on WAIS-RC similarities, a measure of executive function, compared to individuals with val/val genotype. Subsequent ANCOVA analysis revealed that COMT genotype interacted with sex and daily levodopa equivalent dose (LED) to influence executive function. Further stratified analysis showed that the lower-activity COMT met/met genotype has a detrimental effect on executive function among women.nnnCONCLUSIONSnOur results demonstrate that COMT Val158Met polymorphism is probably not associated with increased risk of PD, but has an effect on prefrontal executive function interacting with gender and dopaminergic medication.

Striatal silent lacunar infarction is associated with changes to the substantia nigra in patients with early-stage Parkinson's disease: A diffusion kurtosis imaging study.

A recent study has shown that striatal silent infarction may occur secondary to the degeneration of dopaminergic neurons in the substantia nigra (SN) of mice. However, it is uncertain whether this phenomenon occurs in patients with early-stage Parkinsons disease (PD) and can be detected by diffusion kurtosis imaging (DKI). A total of 72 untreated patients with early-stage PD underwent conventional MRI and DKI. Participants were divided into control and striatal silent lacunar infarction (SSLI) groups. The differences in mean kurtosis (MK) values of the SN, Hoehn-Yahr (H-Y) staging, and Unified Parkinsons Disease Rating Scale (UPDRS) III score between groups, were analyzed. Linear regression analysis was used to correlate age, SSLI count, silent lacunar infarction count in other brain areas and age-related white matter change score with MK values of the SN. Spearman correlation coefficient analysis was used to correlate MK values of the SN and SSLI count with H-Y staging and UPDRS III score. There was no significant difference in the severity of disease between two groups; however, MK values of the SN with SSLI present were significantly higher than in SN without SSLI. In addition, SSLI count had linear correlation with MK values of the SN, which had positive correlation with H-Y-staging and UPDRS III score. SSLI is associated with structural changes to the SN in patients with early-stage PD, detectable by DKI, and may aggravate their motor impairments.