The hypothesis that early degeneration of the pedunculopontine nucleus (PPN) may be related to nigral degeneration has opened new avenues of basic research for this disease. It is not known how the motor function and nigrostriatal gene expression of TH, VMAT2 and DAT behave in an intermediate term (30 days) following the pontine lesion.
Anti-LGI1-associated autoimmune encephalitis is a limbic system pathology characterized by persistent seizures, cognitive and neuropsychiatric symptoms and is treated with immunomodulators depending on the autoimmune etiology.
Down syndrome (DS) is the most frequent genetic disease characterized by several neuropathological features including alteration in neurogenesis, mental disability, cognitive impairments, learning-memory deficits and early onset of Alzheimer's disease (AD). Over expression of chromosome 21 genes, localized in Down Syndrome Critical Region (DSCR), is the main cause of DS neuropathological features.
Purpose: Cognitive changes in Parkinson's disease (PD) can occur at any stage of the disease and have been shown to significantly impact well-being and life participation.The nature and pattern of cognitive decline in PD remains unclear due to the heterogeneity of symptoms and lack of a clear explanatory model.This review aims to draw attention to several theoretical models of cognitive decline in PD to deepen our understanding of the complex milieu of symptoms and begin to offer clinical implications for rehabilitation fields. Method:The domains of cognition typically affected by PD are reviewed along with key aspects of five prominent models of cognition in PD.Implications are discussed through the lens of cognitive heterogeneity and clinical practice.Results: Multiple cognitive domains are vulnerable to PD neuropathology, however, variability exists in the presence and severity of functional changes.Theoretical models that highlight disease progression, vulnerable neural networks, and neurotransmitter involvement provide insight into the variability of cognitive changes. Conclusion:Although one single model cannot account for the wide variability in presentation and rate of cognitive decline in PD, consideration of multiple models provides important insight for research and clinical practice, such as the delineation of cognitive phenotypes.
Parkinson’s disease (PD) is the second most common neurodegenerative disease, presenting with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and motor symptoms. Categorized as a synucleinopathy, the pathological hallmark of PD is intracellular filamentous Lewy bodies (LB), which are formed from protopathic aggregates. The most prevalent of these proteins is the presynaptic protein ɑ-synuclein (α-syn). While commonly attributed to neuronal death in SNpc, postmortem studies have shown α-syn immunoreactivity and LB pathology in the peripheral, central, and enteric nervous system (ENS). While the etiology of misfolded α-syn is unknown, various gut microbiota and substrates are associated with α-syn dysfunction. Gastrointestinal (GI) dysfunction, a common feature in the prodromal phase of PD patients, and histological evidence have led to the Braak hypothesis of misfolded α-syn commencement in the ENS and propagation to brainstem nuclei including the SNpc via the vagus nerve. Altered or stressed gut environment is thought to contribute to the misfolding of α-syn that subsequently initiates or spurs its propagation from the gut myenteric plexus. This review covers clinical and pre-clinical evidence of the involvement of enteric α-syn in PD related to GI dysfunction and brain pathology.
Alzheimer's disease (AD), the most common type of dementia or neurodegenerative diseases since the beginning of the past century when it was coined by the German psychiatrist, Alois Alzheimer in 1901 holds an allusive etiology, and as a result failed most treatment and prevention strategies. Despite the common belief among the experts of AD being a genetic disease, the genetic heritability of this disease has such a wide range of 50-80% in twin and family studies that questions the totality of it as being hereditary.
Perhaps the reason behind this is that epilepsy nowadays has become more than just transient seizures that are treated with drugs to put an end to seizure recurrence, but rather it is a disease that permeates all aspects of the patient's life.
The apolipoprotein E4 (APOE4) allele represents the single greatest risk factor for late-onset Alzheimer's disease (AD) and accumulating evidence suggests that fragmentation with a toxic-gain of function may be a key molecular step associated with this risk. Recently, we demonstrated strong immunoreactivity of a 151 amino-terminal fragment of apoE4 (E4-fragment) within the nucleus of microglia in the human AD brain. In vitro, this fragment led to toxicity and activation of inflammatory processes in BV2 microglia cells. Additionally, a transcriptome analysis following exogenous treatment of BV2 microglia cells with this E4 fragment led to a > 2-fold up regulation of 1,608 genes, with many genes playing a role in inflammation and microglia activation. To extend these findings, we here report a similar transcriptome analysis in BV2 microglia cells following treatment with full-length ApoE4 (FL-ApoE4). The results indicated that full-length ApoE4 had a very small effect on gene expression compared to the fragment. Only 48 differentially expressed genes (DEGs) were identified (p < 0.05, and greater than 2-fold change). A gene ontology analysis of these DEGs indicated that they are not involved in inflammatory and activation processes, in contrast to the genes up regulated by the E4-fragment. In addition, genes that showed a negative fold-change upon FL-E4 treatment typically showed a strong positive fold-change upon treatment with the fragment (Pearson's r = -0.7). Taken together, these results support the hypothesis that a key step in the conversion of microglia to an activated phenotype is proteolytic cleavage of FL-ApoE4. Therefore, the neutralization of this amino-terminal fragment of ApoE4, specifically, may serve as an important therapeutic strategy in the treatment of AD.
The incidence of Multiple sclerosis disease is rapidly increasing worldwide, for instance, across Asia, the utmost growth was confirmed in Japan from 1,000 in 1980 to more than 20,000 people in 2019 [1]. The phenomenon of “Westernization” in Asian countries which includes a specific choice of food and lifestyle was related to the higher prevalence of MS in Asia’s population which almost supports new findings on the great influence of gut and its microbiota in people worldwide. The current conventional therapy helps to prolong the periods between attacks and relapses, but in fact, does not slow down the disease progression and impact on physical activities which eventually leads to disabilities. The development of a new approach and data is highly required with the opportunity to avoid immunity suppression. This review article shares information on the complex integrative approach of the management of MS cases with the application of immune-modulating peptides, mitochondria derived neural peptides, precursor stem cells, active specific immunotherapy therapy and diet. The results showed a regeneration effect, stable prolonged remission, a reversal of symptoms, reduction of side effects, high efficacy of reduction of MS lesions as well as safety of combination (ongoing and integrative) approach. RevieW ARTiCLe
The patient was a 64-year-old man with movement disorder and dysarthria, which was referred to the Speech Therapy Clinic of Hazrat Rasoul Hospital affiliated with Iran University of Medical Sciences. The level of education of the patient was PhD in political science and his job was to teach part-time at the university as well as high school management. The onset of obvious symptoms in this patient dates back to about 4 years and 7 months ago. At that time, he was not able to keep the names of his students and colleagues as before, and he experienced the first problems and long pauses during speech.
Purpose:The motor and non-motor deficits of Parkinson's disease (PD) can cause daily challenges and have been associated with reduced health-related quality of life (HrQoL).A number of variables have been consistently, though not unequivocally, identified as important in influencing overall HrQoL in individuals with PD, such as demographic factors, cognitive decline, and level of motor impairment.However, the presence and severity of dysarthria is often overlooked, despite the potentially adverse influence on HrQoL.The primary purpose of this study was to understand the predictors of HrQoL, as well as self-perceived communication participation, in individuals with PD who have dysarthria.Methods: Twenty-seven participants with Parkinson's disease and dysarthria completed the study.Linear regression was used to determine the predictive ability of motor function, speech intelligibility and cognitive performance on HrQoL and communicative participation; models were run with and without the demographic/clinical variables of age, sex, years of education, disease duration, and depression scores.Results: HrQoL was significantly predicted by the severity of motor symptoms and the combination of cognitive functioning with age, whereas communicative participation was only predicted by monologue intelligibility.Conclusions: This preliminary study suggests that the HrQoL of individuals with dysarthria from PD may be most affected by overall motor function, while participation in life situations may be most influenced by decreased conversational intelligibility. ReSeARCh ARtiCleCheck for updates people globally [1] and is considered a complex multidimensional disorder that leads to a broad array of motor and non-motor symptoms [2].The primary motor characteristics of PD include tremor, rigidity, bradykinesia/akinesia, and postural instability; secondary motor characteristics include dysarthria, dysphagia, and micrographia.Non-motor symptoms emerge from numerous domains, including cognitive, neuropsychiatric, sleep, sensory, and autonomic systems [3], and are present in the majority of people with PD.Both the motor deficits [4,5] and non-motor deficits [6-8] can cause daily challenges and have been associated with reduced quality of life.The motor impairments often lead to decreased physical mobility, which is the most commonly reported problem among people with PD [4,5].Additionally, motor impairments negatively impact the ability to complete activities of daily living (ADLs) which can lead to a decreased level of independence.Non-motor deficits, particularly cognitive impairment, are commonly observed across the course of PD, with approximately 15%-25% of people presenting with challenges in the early stages of the disease and 50-80% of people demonstrating dementia over the course of the disease [9,10].The characteristics of cognitive impairment vary by person, but may include a decline in executive function, attention, memory, working memory, and visuospatial functioning [10][11][12][13].Cognitive deficits in individuals with PD have been associated with decreased independence, decreased participation in communication exchanges, and increased levels of de-* p< 0.
Spinocerebellar ataxia 2 is a rare neurodegenerative disease characterized by a complex neurological presentation of ataxia of adult onset with an autosomal dominant inheritance caused by an abnormal expansion of trinucleotide CAG repeat.
The mammalian brain depends on a continuous supply of oxygen and glucose to meet metabolic demand. Adaptive mechanisms allow brain cells to exist under conditions of moderately low oxygen when ‘idling’ or exposure to high altitude as well as elevated oxygen delivery when activated. Regulation involves numerous intrinsic and extrinsic adaptive mechanisms that serve to maintain metabolic homeostasis. Under conditions of chronic low oxygen (10%) endogenous changes in CNS angiodynamics help promote survival. We questioned whether endogenous adaptation to a stressor such as mild changes in respiratory oxygen altered chronic inflammation in an animal model of multiple sclerosis (MS) experimental autoimmune encephalomyelitis (EAE). We previously reported that when mice were exposed to chronic mild hypoxia at the time of immunization with myelin oligodendrocyte glycoprotein (MOG) they exhibited a delay in disease onset and a decrease in disease severity. Changes in clinical EAE were associated with decreased T cell infiltration into the spinal cord as well as altered regulatory T-cell subsets. In this study, we examine the effect of in vivo exposure to chronic mild hypoxia after the development of disease symptoms. Mice were exposed to 10% normobaric oxygen after the clinical symptoms reach to score 2. Exposure to mild hypoxia ameliorated chronic inflammatory activity and was associated with reduction in clinical score. Further we found evidence that exposure to hypoxia increased the ratio of Foxp3+ Tregs and IL-10+ and Blimp1+ T cells following exposure to low oxygen. In addition, chronic low oxygen decreased evidence of endothelial activation.
We interviewed a stratified random sample of 1,152 non-institutionalized elderly (65 years and older) residents of El Paso County, Texas, during 2000-2001. This sample represents 84 percent of respondents originally contacted for interview. The survey instrument was translated into Spanish through cross-translation. In-home interviews were conducted in Spanish or English, depending on respondents' preference. Twenty-four census tracts were randomly selected from 94 census tracts specified in the 1990 census after stratification for median income and ethnic composition. Specifically, eight census tracts were randomly selected from the lower, middle, and upper-middle income categories.
Objective: Currently, Parkinson's disease (PD) is becoming more common among younger people of ages from 30 – 40 years. The incidence is higher among patients with higher body mass index (BMI), and some reports had it that Obesity is a risk factor for PD while some reported that there is no relationship between obesity and PD. PD patient at the time of diagnosis has an above-normal BMI but which goes below normal as the disease progresses. Therefore, it is essential to explore the relationship between PD and Obesity
In this study we analyzed 81 patients who referred to our outpatient clinic diagnosed as early onset Alzheimer's disease (EOAD) between January 2014-January 2017 and had been performed Sanger sequencing analysis for exons 16 and 17 of APP, and all coding exons of PSEN1 and PSEN2 genes. All sequenced patients were demented, and of the 81 patients, 49 were female and 32 were male. The average age at admission and mean age of onset were 54.8 (Patients were referred to our outpatient clinic at the time of diagnosis). Before testing, written informed consent was obtained from the patients and/or family members, and ethics committee approval was received for this study from the Ethics Committee of Dokuz Eylul University Medicine Faculty. We found seven PSEN1and four PSEN2 mutations, and we did not find any APP mutations.
Physical activity has the potential to improve cognition for those with dementia, as demonstrated by randomised controlled trials lasting at least 6 weeks. Research is yet to explore the acute cognitive effects of physical activity for people with dementia. Acute resistance physical activity with healthy late-middle aged individuals has been shown to facilitate general cognition, as well as benefit executive function specifically. This study therefore aimed to establish if people with dementia experience cognitive benefits from acute resistance physical activity over and above a social control.
Keyword used in searching for similar articles on PubMed were, Obesity, hyperlipidemia, Metabolic syndrome (MetS), Neurodegenerative disorders, Parkinson's diseases (PD). Papers from 2014-2019 related were compiled. Cases at Zhenjiang First people's hospital similar was compiled to draw conclusions.
Alzheimer is one of the most common causes of dementia that influence nerve cells in various parts of the brain. Pathologically it is caused because of intracellular neurofibrillary tangles and extracellular amyloidal protein and results in the deposition of plaques which obstruct the communication between the nerve cells resulting in this neurodegenerative disease.
A 69-year-old Caucasian female experienced multiple episodes of full-body tremors during the extension phase of the clinical study. The investigational drug was taken in the mornings. The patient reported that the AE started six months prior with episodes occurring 1-2 times per week eventually escalating almost daily and was more apparent during midnight hours and upon waking up. Further review of progress notes states that the patient denied the AE and even stated full compliance and no complaints as per protocol before admitting to three missed doses later on.
