Association of low serum BDNF with depression in patients with Parkinson's disease.

OBJECTIVE: Increasing evidence shows that brain-derived neurotrophic factor (BDNF) plays a critical role in the development of depression and the mechanisms of antidepressant. Parkinson disease (PD) is associated with depression and decreased BDNF. The aim of the present study was to examine the association of BDNF with depression in PD, which has not been investigated. METHODS: We recruited 96 PD patients with (n = 46) and without depression (n = 50) and 102 healthy controls and measured the serum BDNF levels in both groups. Zung Self-Rating Depression Scale (SDS) was administered for the severity of depression and Hoehn-Yahr staging scale for motor abilities in PD patients. RESULTS: Serum BDNF levels were significantly lower in PD patients than healthy controls (p < 0.01). Also serum BDNF levels were significantly decreased in PD patients with than without depression (p < 0.01). BDNF levels were negatively associated with SDS in both PD patients with and without depression (both p < 0.01). Multiple regression analysis confirmed that in either PD with or without depression group, BDNF was an independent contributor to SDS (both p < 0.05). CONCLUSIONS: Our findings suggest that decreased serum BDNF may be involved in the pathophysiology of depression in PD patients.

Low BDNF is associated with cognitive impairments in patients with Parkinson's disease.

OBJECTIVE: Increasing evidence show that brain-derived neurotrophic factor (BDNF) plays a critical role in neuroplasticity in the hippocampus that is related to learning and memory. Parkinson disease (PD) is associated with impairment of cognitive function that may evolve from decreased BDNF. The aim of the present study was to examine the association of BDNF with cognitive impairment in PD. METHODS: We compared 97 PD patients to 102 healthy controls on serum BDNF and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Hoehn-Yahr staging test was used to assess motor abilities. RESULTS: Serum BDNF levels were significantly lower in PD patients than in healthy controls (p < 0.01). Cognitive performance shown on the RBANS total and all of its five index scores were significantly lower in PD patients than normal controls (all p < 0.05). For the patients only, BDNF was positively associated with all five index and total scores of RBANS. CONCLUSIONS: Our findings suggest extensive cognitive impairments and decreased BDNF in PD patients. Moreover, decreased BDNF is associated with cognitive deficits of Parkinson's disease.

Neurotoxicity of cerebro-spinal fluid from patients with Parkinson's disease on mesencephalic primary cultures as an in vitro model of dopaminergic neurons.

Parkinson's disease is a degenerative disorder of the central nervous system. In spite of extensive research, neither the cause nor the mechanisms have been firmly established thus far. One assumption is that certain toxic substances may exist in the cerebro-spinal fluid (CSF) of Parkinson's disease patients. To confirm the neurotoxicity of CSF and study the potential correlation between neurotoxicity and the severity of Parkinson's disease, CSF was added to cultured cells. By observation of cell morphology, changes in the levels of lactate dehydrogenase, the ratio of tyrosine hydroxylase-positive cells, and the expression of tyrosine hydroxylase mRNA and protein, the differences between the two groups were shown. The created in vitro model of dopaminergic neurons using primary culture of mouse embryonic mesencephalic tissue is suitable for the study of neurotoxicity. The observations of the present study indicated that CSF from Parkinson's disease patients contains factors that can cause specific injury to cultured dopaminergic neurons. However, no obvious correlation was found between the neurotoxicity of CSF and the severity of Parkinson's disease.

Serum 25-hydroxyvitamin D predicts severity in Parkinson's disease patients.

In recent years, increasing evidence has shown that individuals with Parkinson's disease (PD) have lower levels of 25-hydroxyvitamin D [25(OH) D] relative to healthy controls. We therefore evaluated the relationship between serum 25(OH) D levels and severity in Chinese patients with a Parkinson's disease. From July 2010 to June 2012, consecutive PD patients admitted to the Department of Neurology of General Hospital, Tianjin Medical University, were identified. Clinical information and disease duration were collected. Serum level of 25(OH) D was measured at baseline. PD severity was assessed at admission using the Hoehn and Yahr (HY) stage and Unified Parkinson's Disease Rating Stage (UPDRS) total score. The results indicated that the mean serum 25(OH) D levels were significantly lower in PD patients as compared to normal cases (P < 0.001). There was a negative correlation between levels of 25(OH) D and the disease duration [r (spearman) = -0.124, P = 0.041]. There was a significant negative relationship between circulating serum 25(OH) D levels and severity of Parkinson's disease evaluated by HY stage (P = 0.030) and UPDRS Stage (P = 0.000) even after multivariate adjustment for possible confounders: age, gender, disease duration, levels of Ca, ALP, blood glucose, and seasons. These results suggest that lower 25(OH) D levels may be associated with severity of PD in Chinese patients.

[Clinical analyses of perinuclear antineutrophil cytoplasmic antibody associated hypertrophic pachymeningitis].

OBJECTIVE: To explore the clinical characteristics, diagnosis, treatment and prognosis of perinuclear antineutrophil cytoplasmic antibody (p-ANCA) associated hypertrophic pachymeningitis. METHODS: A retrospective study was performed for 6 inpatients with p-ANCA associated hypertrophic pachymeningitis at our hospital from 2005 to 2012. RESULTS: There were 3 males and 3 females with an age range of 52 - 68 years. The main clinical manifestations included headache and multiple cranial neuropathies. Erythrocyte sedimentation rate, C-reactive protein, titer of myeloperoxidase (MPO)-ANCA and protein in cerebrospinal fluid were uniformly elevated in all 6 patients during active phase while cytoplasmic(c)-ANCA was all negative. Head magnetic resonance imaging (MRI) enhancement scan had a high diagnostic sensitivity. Different parts of dura were all thickened and obviously enhanced. Glucocorticoid was uniformly effective. During the follow-up period, 2 cases relapsed and received immunosuppressive agents. CONCLUSION: The disease should be considered in elderly patients with headache, cranial nerve injury and positive p-ANCA. And head MRI enhancement scan is helpful for diagnosis.

[Effects of entacapone on plasma homocysteine in Parkinson's disease patients on levodopa].

OBJECTIVE: To explore the effects of entacapone on the plasma level of homocysteine (Hcy) in Parkinson's disease (PD) patients on levodopa. METHODS: This cross-sectional study was made up of 4 groups, i.e. 'L + E' group (primary PD patients on levodopa and entacapone), 'L' group (primary PD patients on levodopa alone), 'L(-)' group (primary PD patients never on levodopa) and control group (people without PD or any other nervous system diseases). They were randomly selected from the PD patient database of our department in September 2012. At the beginning, 60 cases were selected for each group. The C677T genotypes of methylenetetrahydrofolate reductase (MTHFR) were identified and the plasma concentrations of Hcy, folic acid and vitamin B12 detected in each subject. Then group t test, single factor analysis of variance and χ(2) test were used for statistical analysis by SPSS 11.5 software. RESULTS: Among 240 early subjects, 98 cases with CC genotype at 677 site of MTHFR gene were finally recruited. Statistical analysis revealed no differences in age, gender, plasma concentrations of folic acid and vitamin B12 among the groups. The PD duration of 'L + E' group (96 ± 21 months) were the longest among 3 groups, followed by those of 'L' group (51 ± 17 months) and 'L(-)' group (21 ± 6 months). The treatment duration and daily dose of levodopa in 'L + E' group (77 ± 22 months, 765 ± 110 mg) were all higher than those in 'L' group (42 ± 14 months, 673 ± 73 mg). The plasma Hcy concentrations of 'L + E' group (15.1 ± 3.1 µmol/L) were lower than those of 'L' group (20.4 ± 4.7 µmol/L), but still higher than those of 'L(-)' group (12.2 ± 2.4 µmol/L) and control group (9.1 ± 2.2 µmol/L). The Hcy concentrations of 'L(-)' group were also higher than those of control group. CONCLUSION: Entacapone increases the bioavailability of levodopa and simultaneously alleviates partially its resulting hyperhomocysteinemia.

[A study on the cerebral glucose metabolism in progressive supranuclear palsy].

OBJECTIVE: To study the regional cerebral glucose utilization with (18)F-fluorodeoxyglucose (FDG) PET and to investigate the correlation between cerebral glucose metabolism and the clinical characteristic of progressive supranuclear palsy (PSP). METHODS: A total of 13 patients with PSP and 30 matched healthy controls were performed (18)F-FDG PET imaging at rest state. Visual inspection and statistical parametric mapping (SPM) were used to investigate regional cerebral metabolic rate of glucose (rCMRglc). RESULTS: Based on the visual inspection, PET imaging in the PSP patients showed that the focal hypometabolic areas mainly included the bilateral frontal cortex, midbrain and subcortical structures. Compared to the controls, voxel-based analysis showed that the regional glucose metabolism decreased in bilateral superior, middle frontal gyrus, cingulate gyrus, midbrain and subcortical structures including basal ganglion and thalamus, which were consisted with the clinical characteristics, such as vertical gaze palsy, pseudobulbar palsy, postural instability, axial rigidity, dementia and so on. CONCLUSION: (18)F-FDG PET imaging is helpful for the early diagnosis of PSP.

Association of the manganese superoxide dismutase gene Ala-9Val polymorphism with clinical phenotypes and tardive dyskinesia in schizophrenic patients.

OBJECTIVE: Several recent studies that have investigated the genetic association between the manganese superoxide dismutase (MnSOD) gene Ala-9Val single-nucleotide polymorphism (SNP) and tardive dyskinesia (TD) have produced conflicting results. This study was to investigate whether this SNP was associated with clinical phenotypes and antipsychotic-induced tardive dyskinesia (TD) in schizophrenia in a genetically homogeneous Han Chinese inpatient population. METHODS: Genotyping was performed for the MnSOD gene Ala-9Val SNP in Chinese schizophrenia patients with (n=176) and without TD (n=346). The severity of TD was assessed using the abnormal involuntary movement scale (AIMS), and psychopathology using the Positive and Negative Syndrome Scale (PANSS). RESULTS: The frequencies of genotypes and alleles did not differ significantly between schizophrenic patients with and without TD (both p>0.05). Also, there was no significant difference in the AIMS total score between the Val/Val and Ala allele carrier groups (p>0.05). However, the PANSS negative symptom subscore was significantly higher in patients with Val/Val genotype (21.8+/-7.3) than those with Ala alleles (20.1+/-7.7) (t=2.32, p=0.03). CONCLUSION: While the MnSOD gene Ala-9Val polymorphism did not play a major role in the susceptibility to TD in schizophrenic patients, it might be associated with negative symptoms of schizophrenia.

[Cerebral glucose metabolism in Parkinson's disease with dementia].

OBJECTIVE: To assess the regional cerebral glucose utilization and the imaging characteristic of Parkinson's disease with dementia (PDD) with (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). METHODS: Questionnaire survey, mini-mental state examination (MMSE), physical examination, and FDG PET on brain at rest state were performed on 20 patients with PDD, 13 males and 7 females, aged (70 +/- 6), and sex- and age-matched 8 patients with non-demented PD, and 30 healthy parsons. Visual inspection and statistical parametric mapping (SPM) were used to investigate the regional cerebral metabolic rate of glucose (rCMRglc) and the distribution of the tracer. RESULTS: The MMSE score of the PDD group was (27.5 +/- 2.4), (10 - 24), significantly lower than those of the non-PDD group [(27.5 +/- 2.4) (22 - 30)] and control group [(27.9 +/- 2.2) (21 - 30)] (F = 60.31, P = 0.000). There were no significant differences in Hoehn-Yahr staging and disease courses between the two PD groups (P > 0.05). Visual inspection showed that there were no significant focal hypometabolic areas in the imaging of the non-demented PD patients, while compared to the controls, the rCMRglc levels of the PDD patients decreased in bilateral superior parietal lobules (BA 7), inferior parietal lobules (BA 40, 39), superior frontal gyri (BA 6), middle frontal gyri (BA 6, 8, 9), middle temporal gyri (BA 21), cuneate lobes (BA 17, 18, 19), cingulate cortices (BA 31), lingual gyri (BA 19) basal ganglia, and thalamus. According to the severity of memory impairment and the onset of hallucination, the subtype of PDD was classified into memory impairment dominant group (MD) and hallucination dominant group (HD). The rCMRglc of MD subgroup decreased significantly in the parietotemporal association cortex, especially in the precuneus lobe. The rCMRglc of the HD subgroup decreased significantly in the occipital cortex. There were no significant differences in MMSE score and Hoehn-Yahr staging between the MD and HD groups (both P > 0.05), while the age of the HD subgroup was significantly lower, and the disease duration of the HD subgroup was significantly longer than those toe MD group (both P < 0.05). CONCLUSIONS: (18)F-FDG/PET imaging is helpful to the diagnosis of PDD and may help investigate the potential pathophysiology of PDD.

[Association between estrogen receptor beta gene polymorphisms and Parkinson disease].

OBJECTIVE: To investigate the association between two estrogen receptor (ER) beta gene polymorphisms and Parkinson disease (PD) as well as Parkinson disease with dementia (PDD) in Chinese people. METHODS: Peripheral blood samples were collected from 115 PD patients (including 26 PDD cases), 56 males and 55 females, aged 64 +/- 10, and 116 sex and age-matched healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to analyze the polymorphism of the fifth exon RsaI and the eighth exon AluI of ERbeta gene. Te relationship between each genotype or allele frequencies and PD/PDD was analyzed using chi-square test. RESULTS: There was no difference in the polymorphism of ERbeta genes AluI and Rsa I between the PD group and control group and between the PDD group and control group (all P > 0.05). CONCLUSION: Genetic variations from AluI and RsaI digestion in ERbeta gene do not affect the risk of PD and PDD.

[Association of the polymorphism in alpha-2 macroglobulin gene with essential tremor and Parkinson's disease].

OBJECTIVE: To study the association of two polymorphisms of alpha-2 macroglobulin gene (A2M), a 1000G/A in exon 24 and a pentanucleotide insertion/deletion (I/D) in the 5'splice site in exon 18, with Parkinson's disease (PD) and essential tremor (ET) in North China. METHODS: Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to investigate 87 cases of Parkinson's disease (PD),73 cases of ET and 100 randomly selected healthy control subjects. RESULTS: (1) The allelic and genotypic distributions of A2M G/A were significantly different among the PD, ET patients and controls (P<0.05). The allele G and genotype GA in PD patients were significantly higher than those in ET patients or controls (P<0.05). There was no statistically significant difference between ET patients and controls in allelic and genotypic distribution (P>0.05). (2) The differences in allelic and genotypic distributions of A2M I/D among PD, ET patients and selected controls were found to be of no statistical significance (P>0.05). CONCLUSION: (1) The polymorphism at the site of G/A might be associated with PD, but there might be no genetic association of polymorphism at this site with ET. (2) There might be no association of polymorphism at the site of I/D with PD and ET in North China.