Weak central coherence in patients with Alzheimer’s disease

Central coherence refers to the ability to interpret details of information into a whole.To date,the concept of central coherence is mainly used in research of autism,Asperger’s syndrome and recently in the research on eating disorders.The main purpose of the present study was to examine central coherence in patients with Alzheimer’s disease.Nine Alzheimer’s disease patients and ten age-and gender-matched control subjects,who differed significantly in neurological assessment,were shown a picture of a fire.Compared to control subjects,the Alzheimer’s disease patients described the picture in a fragmented way by mentioning details and separate objects without perceiving the context of the fire.In conclusion,patients with Alzheimer’s disease are at the weak end of central coherence,and hence suffer from a fragmented view of their surroundings.The findings have important clinical implications for the understanding of patients with Alzheimer’s diseaseand also for the possibility of caregivers to meet the Alzheimer’s disease individual in an appropriate way in the everyday care.     

Health-related quality of life in Parkinson’s disease patients in northeastern Sicily, Italy An ecological perspective

Parkinson’s disease has a negative impact on health-related quality of life in Parkinson’s disease patients. Depression, cognitive impairment, coping strategies, dyskinesia, gait disorders and complications of dopaminergic drugs are the variables that most affect health-related quality of life. The ecological model of human development focuses attention on both individual and social environmental factors as targets for health interventions. From this perspective, the aim of this cross-sectional survey was to evaluate the influence of gender, family size and perceived autonomy on health-related quality of life in Parkinson’s disease patients in northeastern Sicily, Italy. Ninety Parkinson’s disease patients, attending the Movement Disorders Clinic at IRCCS Centro Neurolesi "Bonino-Pulejo" (Messina), were consecutively enrolled. The Unified Parkinson Disease Rating Scale motor subscale (UPDRS-Ⅲ) scores, the Parkinson Disease Questionnaire-39 Item scores (as a disease-specific measure of health-related quality of life), scores on the Short Form (36) Health Survey Questionnaire (as a generic measure), and answers to a brief checklist were recorded. A total of 85 Parkinson’s disease patients (49% males and 51% females; mean age 70.8 ± 8.6 years; mean UPDRS-Ⅲ 24.15 ± 6.55; mean disease duration 5.52 ± 4.65 years) completed the booklet of questionnaires. In the multivariate regression analysis, we included clinical and social variables as independent predictors of health-related quality of life. Our results suggest a potential compounding effect of ecological intrapersonal and interpersonal levels on health-related quality of life outcomes. Gender, self-evaluated autonomy and family size significantly impacted health-related quality of life. If quality of life is used as an indicator of treatment outcomes, an ecological perspective of the case history will be important to disclose relevant prognostic information and trigger personalized health care interventions.     

Magnetic resonance morphometry of the loss of gray matter volume in Parkinson’s disease patients

Voxel-based morphometry can be used to quantitatively compare structural differences and functional changes of gray matter in subjects.In the present study,we compared gray matter images of 32 patients with Parkinson’s disease and 25 healthy controls using voxel-based morphometry based on 3.0 T high-field magnetic resonance T1-weighted imaging and clinical neurological scale scores.Results showed that the scores in Mini-Mental State Examination and Montreal Cognitive Assessment were lower in patients compared with controls.In particular,the scores of visuospatial/executive function items in Montreal Cognitive Assessment were significantly reduced,but mean scores of non-motor symptoms significantly increased,in patients with Parkinson’s disease.In addition,gray matter volume was significantly diminished in Parkinson’s disease patients compared with normal controls,including bilateral temporal lobe,bilateral occipital lobe,bilateral parietal lobe,bilateral frontal lobe,bilateral insular lobe,bilateral parahippocampal gyrus,bilateral amygdale,right uncus,and right posterior lobe of the cerebellum.These findings indicate that voxel-based morphometry can accurately and quantitatively assess the loss of gray matter volume in patients with Parkinson’s disease,and provide essential neuroimaging evidence for multisystem pathological mechanisms involved in Parkinson’s disease.     

Five-year follow-up of 23 asymmetrical Parkinson’s disease patients treated with unilateral subthalamic nucleus stimulation

In this study, 23 asymmetrical Parkinson’s disease patients were treated with unilateral deep brain stimulation of the subthalamic nucleus and followed up for 5 years. At 5 years after stimulation treatment, Unified Parkinson’s Disease Rating Scale II, III and axial symptom scores in the off-drug condition were significantly increased compared those at baseline. However, total Unified Parkinson’s Disease Rating Scale II, III and axial symptom scores were significantly lower with stimulation-on compared with the synchronous stimulation-off state in off-drug condition, and the motor symptoms of contralateral side limbs were effectively controlled. Only low Hoehn-Yahr stage was correlated with good long-term postoperative improvement in motor symptoms. The mean levodopa-equivalent daily dose after stimulation treatment was significantly lower than that before treatment, but dyskinesias became worse. Our experimental findings indicate that unilateral deep brain stimulation of the subthalamic nucleus is an effective treatment for improving motor symptoms in well selected asymmetrical Parkinson’s disease patients presenting no severe axial symptoms and dyskinesias.     

Baicalin and deferoxamine alleviate iron accumulation in different brain regions of Parkinson’s disease rats

Previous studies found that iron accumulates in the substantia nigra of Parkinson’s disease patients. However, it is still unclear whether other brain regions have iron accumulation as well. In this experiment, rats with rotenone-induced Parkinson’s disease were treated by gastric perfusion of baicalin or intraperitoneal injection of deferoxamine. Immunohistochemical staining demonstrated that iron accumulated not only in the substantia nigra pars compacta, but also significantly in the striatum globus pallidus, the dentate gyrus granular layer of the hippocampus, the dentate-interpositus and the facial nucleus of the cerebellum. Both baicalin and deferoxamine, which are iron chelating agents, significantly inhibited iron deposition in these brain areas, and substantially reduced the loss of tyrosine hydroxylase-positive cells. These chelators also reduced iron content in the substantia nigra. In addition to the substantia nigra, iron deposition was observed in other brain regions as well. Both baicalin and deferoxamine significantly inhibited iron accumulation in different brain regions, and had a protective effect on dopaminergic neurons.     

Dysfunction of two lysosome degradation pathways of α-synuclein in Parkinson’s disease: potential therapeutic targets?

Parkinson’s disease (PD) is pathologically characterized by the presence of α-synuclein (α-syn)-positive intra-cytoplasmic inclusions named Lewy bodies in the dopaminergic neurons of the substantia nigra. A series of morbid consequences are caused by pathologically high amounts or mutant forms of α-syn, such as defects of membrane trafficking and lipid metabolism. In this review, we consider evidence that both point mutation and overexpression of α-syn result in aberrant degradation in neurons and microglia, and this is associated with the autophagy-lysosome pathway and endosome-lysosome system, leading directly to pathological intracellular aggregation, abnormal externalization and re-internalization cycling (and, in turn, internalization and re-externalization), and exocytosis. Based on these pathological changes, an increasing number of researchers have focused on these new therapeutic targets, aiming at alleviating the pathological accumulation of α-syn and re-establishing normal degradation.     

Association of Nurr1 gene mutations with Parkinson’s disease in the Han population living in the Hubei province of China

Nurr1 defects could in part underlie Parkinson’s disease pathogenesis,and Nurr1 gene polymorphism has been found in Caucasian patients with Parkinson’s disease.In this study,heteroduplex technology was applied to compare the DNA sequences of eight exons of Nurr1 among 200 sporadic Parkinson’s disease patients and 200 healthy controls in the Han population in the Hubei province,China.One allele amplified from exon 3 of Nurr1 was polymorphic in five Parkinson’s disease patients(2.5%,5/200),and two individuals had a polymorphic allele amplified from exon 2 (1%,2/200).The anomalous electrophoresis fragment in exon 3 of Nurr1 gene contained a 709C/A missense mutation,and a polymorphic single nucleotide polymorphism at 388G/A was identified in exon 2.Compared with the control group,the Nurr1 gene expression level in the Parkinson’s disease group was decreased,and the Nurr1 gene expression levels in Parkinson’s disease patients carrying the polymorphisms at exons 2 and 3 were significantly decreased.Our data indicate that the single nucleotide polymorphism 388G/A in exon 2 and the 709C/A missense mutation in exon 3 of the Nurr1 gene in the Chinese population might affect the pathogenesis of Parkinson’s disease.     

Neuroprotective role of fibronectin in neuron-glial extrasynaptic transmission

Most hypotheses concerning the mechanisms underlying Parkinson’s disease are based on altered synaptic transmission of the nigrostriatal system.However,extrasynaptic transmission was recently found to affect dopamine neurotransmitter delivery by anisotropic diffusion in the extracellular matrix,which is modulated by various extracellular matrix components such as fibronectin.The present study reviewed the neuroprotective effect of fibronectin in extrasynaptic transmission.Fibronectin can regulate neuroactive substance diffusion and receptor activation,and exert antineuroinflammatory,adhesive and neuroprotective roles.Fibronectin can bind to integrin and growth factor receptors to transactivate intracellular signaling events such as the phosphatidylinositol 3-kinase/protein kinase B pathway to regulate or amplify growth factor-like neuroprotective actions.Fibronectin is assembled into a fibrillar network around cells to facilitate cell migration,molecule and ion diffusion,and even drug delivery and treatment.In addition,the present study analyzed the neuroprotective mechanism of fibronectin in the pathogenesis of Parkinson’s disease,involving integrin and growth factor receptor interactions,and discussed the possible therapeutic and diagnostic significance of fibronectin in Parkinson’s disease.     

The role of autophagy in Parkinson’s disease

Although Parkinson’s disease is the most common neurodegenerative movement disorder, the mechanisms of pathogenesis remain poorly understood. Recent findings have shown that deregulation of the autophagy-lysosome pathway is involved in the pathogenesis of Parkinson’s disease. This review summarizes the most recent findings and discusses the unique role of the autophagy-lysosome pathway in Parkinson’s disease to highlight the possibility of Parkinson’s disease treatment strategies that incorporate autophagy-lysosome pathway modulation.     

Progression of motor symptoms in Parkinson’s disease

Parkinson’s disease(PD)is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms-rigidity,bradykinesia and tremor-due to loss of dopaminergic neurons.The motor symptoms of PD become progressively worse as the disease advances.PD is also a heterogeneous disease since rigidity and bradykinesia are the major complaints in some patients whereas tremor is predominant in others.In recent years,many studies have investigated the progression of the hallmark symptoms over time,and the cardinal motor symptoms have different rates of progression,with the disease usually progressing faster in patients with rigidity and bradykinesia than in those with predominant tremor.The current treatment regime of dopamine-replacement therapy improves motor symptoms and alleviates disability.Increasing the dosage of dopaminergic medication is commonly used to combat the worsening symptoms.However,the drug-induced involuntary body movements and motor complications can significantly contribute to overall disability.Further,none of the currently-available therapies can slow or halt the disease progression.Significant research efforts have been directed towards developing neuroprotective or disease-modifying agents that are intended to slow the progression.In this article,the most recent clinical studies investigating disease progression and current progress on the development of disease-modifying drug trials are reviewed.     

Role of calbindin-D28K in estrogen treatment for Parkinson's disease

Studies have shown that estrogen has neuroprotective effects on the nigrostriatal system. The present study established a Parkinson''s disease model in C57BL/6 mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrapyridine. The mice were subjected to 17β estradiol injection into the lateral ventricle. Immunofluorescence double staining showed that estrogen increased tyrosine hydroxylase and calbindin-D28K expression and co-expression in dopaminergic neurons of midbrain substantia nigra pars compacta of model mice. Behavior experiments showed that estrogen improved swimming and hanging behaviors in this mouse model of Parkinson''s disease.     

A comparison of gray and white matter density in patients with Parkinson's disease dementia and dementia with Lewy bodies using voxel‐based morphometry

Despite clinical and neuropsychological similarities between Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), recent studies have demonstrated that structural and pathological changes are more severe in DLB than in PDD. We used voxel‐based morphometry using a 3‐T MRI scanner to compare gray and white matter densities in 20 patients with probable PDD and 18 patients with probable DLB, who had similar overall severity of dementia and similar demographic characteristics. The gray matter density was significantly decreased in the left occipital, parietal, and striatal areas in patients with DLB compared with patients with PDD. The white matter density was significantly decreased in bilateral occipital and left occipito‐parietal areas in patients with DLB compared with those with PDD. The degree of white and gray matter atrophy was similar in patients with DLB; in contrast, there was markedly less atrophy in the white matter than in the gray matter in patients with PDD. On analyzing the change of WM density relative to that of GM density in patients with DLB compared to those with PDD, the area of WM atrophy in the occipital areas was more extensive than that of GM atrophy. Our data demonstrate that atrophy of both gray and white matter was more severe in patients with DLB and that white matter atrophy relative to gray matter atrophy was less severe in patients with PDD. These data may reflect a difference in the underlying nature of PDD and DLB. © 2009 Movement Disorder Society     

Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease

Introduction

Both polymorphisms and mutations in glucocerebrosidase (GBA) may influence the development of dementia in patients with Parkinson's disease.

Estrogen receptor beta treats Alzheimer’s disease

In vitro studies have shown that estrogen receptor β can attenuate the cytotoxic effect of amyloid β protein on PC12 cells through the Akt pathway without estrogen stimulation. In this study, we aimed to observe the effect of estrogen receptor β in Alzheimer’s disease rat models established by intraventricular injection of amyloid β protein. Estrogen receptor β lentiviral particles delivered via intraventricular injection increased Akt content in the hippocampus, decreased interleukin-1β mRNA, tumor necrosis factor α mRNA and amyloid β protein levels in the hippocampus, and improved the learning and memory capacities in Alzheimer’s disease rats. Estrogen receptor β short hairpin RNA lentiviral particles delivered via intraventricular injection had none of the above impacts on Alzheimer’s disease rats. These experimental findings indicate that estrogen receptor β, independent from estrogen, can reduce inflammatory reactions and amyloid β deposition in the hippocampus of Alzheimer’s disease rats, and improve learning and memory capacities. This effect may be mediated through activation of the Akt pathway.     

Back propagation artificial neural network for community Alzheimer’s disease screening in China

Alzheimer’s disease patients diagnosed with the Chinese Classification of Mental Disorders diagnostic criteria were selected from the community through on-site sampling. Levels of macro and trace elements were measured in blood samples using an atomic absorption method, and neurotransmitters were measured using a radioimmunoassay method. SPSS 13.0 was used to establish a database, and a back propagation artificial neural network for Alzheimer’s disease prediction was simulated using Clementine 12.0 software. With scores of activities of daily living, creatinine, 5-hydroxytryptamine, age, dopamine and aluminum as input variables, the results revealed that the area under the curve in our back propagation artificial neural network was 0.929 (95% confidence interval: 0.868-0.968), sensitivity was 90.00%, specificity was 95.00%, and accuracy was 92.50%. The findings indicated that the results of back propagation artificial neural network established based on the above six variables were satisfactory for screening and diagnosis of Alzheimer’s disease in patients selected from the community.     

Regional gray matter atrophy and neuropsychologcal problems in relapsing-remitting multiple sclerosis

In multiple sclerosis, gray matter atrophy is extensive, and cognitive deficits and mood disorders are frequently encountered. It has been conjectured that focal atrophy is associated with emotional decline. However, conventional MRI has revealed that the pathological characteristics cannot fully account for the mood disorders. Moreover, there is no correlation between cognitive disorders and MRI results in clinically isolated syndromes or in cases of definite multiple sclerosis. In this casecontrol study, voxel-based morphometric analysis was performed on 11 subjects with relapsing-remitting multiple sclerosis, and the results show that these patients exhibit gray matter atrophy. Moreover, the gray matter atrophy in the superior and middle gyri of the right frontal lobe in patients with multiple sclerosis was correlated with scores from the Hamilton Anxiety Rating Scale. The scores obtained with the Repeatable Battery for the Assessment of Neuropsychological Status were associated with gray matter atrophy in the middle gyrus of the left frontal lobe, the superior and middle gyrus of the right frontal lobe, the middle gyrus of the left cingulate, the superior and middle gyri of the left frontal lobe, and the triangular area of the left frontal lobe. However, there was no statistical significance. These findings suggest that the cingulate and frontal cortices of the dominant hemisphere are the most severely atrophic regions of the brain, and this atrophy is correlated with cognitive decline and emotional abnormalities.