摘要:Alzheimer disease is one of the commonest neurological diseases which is characterized by amyloid plaques accumulation in multiple brain regions. This study investigated the potential neuroprotective effect of artesunate on aluminum induced neurotoxicity vs memantine in rats. 40 male albino Wistar rats were divided randomly into 4 groups as follow: Group 1 negative control, group 2 positive control group induced by ammonium chloride, group 3 rats treated by NH4Cl + artesunate solution, group 4 rats treated by NH4Cl + memantine S.C. spatial Memory and Learning were evaluated using Morris Water Maze (MWM) test. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured in cerebral cortex tissue homogenate. Tumor necrosis factor-α (TNFα) and interleukin-1 beta (IL-1β) concentrations were measured in rat cerebral cortex tissue homogenate using rat enzyme linked immunosorbent assay (ELISA) kits. Real-time quantitative reverse transcription-polymerase chain reaction (Real-time qRT-PCR) for Caspase-3, Bcl-2 and iNOS gene expression was measured in rat cerebral cortex. Slices from cerebral cortex were studied by histopathological examination. Artesunate significantly decreased MDA level and inhibited iNOS, caspase and upregulated Bcl-2 gene expression in cerebral cortex. ART increased significantly antioxidant level GSH, and decreased significantly TNF-alpha and IL-B levels. It reduced significantly 1ry retention latency, 2ry retention latency and initial acquisition latency. It also improved brain histopathology and decreased amyloid plaque deposition. ART exerted neuroprotective effect through oxidative stress correction and enhancement of antiapoptotic markers in neuronal cells of the cerebral cortex.
摘要:Introduction: The purpose of this study is to evaluate discriminating power of two texture analysis, linear discriminant analysis and nonlinear discriminant analysis, in classifying atrophy of Alzheimer’s disease and atrophy of aging. Methods: The database included 24 regions of interest of Alzheimer patients and 24 regions of interest of aging people in hippocampus region. Linear discriminant analysis and nonlinear discriminant analysis were used for texture analysis. The first nearest neighbor classifier was applied to features resulting from linear discriminant analysis. Nonlinear discriminant analysis features were classified by using an artificial neural network. The confusion matrix and Receiver Operating Characteristic (ROC) curve analysis were used to examine the performance of texture analysis method. Result: Nonlinear discriminant analysis indicates the best performance for classification of atrophy of Alzheimer’s disease and atrophy of aging. Conclusion: Our result showed computer aided diagnosis has high potential discriminating power in classifying Alzheimer’s disease in early stage.
摘要:Aim: In this review paper we propose a method to make an early diagnosis of the Alzheimer’s Disease (AD), the most common form of neurodegenerative dementia. Background: Glymphatic System (GS) is the main means of eliminating waste substances in the central nervous system (CNS);if it does not work properly, waste substances accumulate in CNS until to cause AD. Basal Forebrain is the most important component of a much broader system of cholinergic cells distributed throughout the Central Nervous System (CNS). This structure regulates attention, learning and memory and its destruction is considered responsible for the cognitive AD alterations. The characteristics of AD patients, that interest us most, are the lack of Acetylcholine, and the Orexin excess;we think that the hypothalamus produces more Orexin to stimulate cholinergic cells, indispensable for a correct CNS functioning. We want to identify these patients by detecting the Orexin excess. Early Diagnosis Model. Of course we could take a cerebrospinal fluid sample and dose Orexin but this method is risky and painful for the patient’s health, therefore unsuitable for large numbers of patients. We propose a fairly simple method for the early diagnosis of AD: if we temporarily eliminate the Orexin excess, with Dual Orexin Receptor Antagonist (DORA), i.e. Suvorexant, we can intercept the Orexin increase and demonstrate the decrease in Acetylcholine with a Functional Magnetic Resonance or a Polysomnography, many years before the AD symptoms occur.
摘要:Alzheimer’s disease (AD) is the common cause of dementia which shows the neuro-pathologies like an accumulation of amyloid-β (Aβ) and degeneration of cholinergic neuron. Olfactory bulbectomized (OBX) mice show some of AD features, so they have been used to research as AD model. Mesenchymal stem cells (MSCs) can differentiate into many kinds of cells, including neuronal cells. In this study, we intranasally administrated the conditioned medium derived from cultured umbilical cord (UC) MSCs. The intranasal administration of the MSCs medium restored the cognitive impairment observed in OBX mice. In addition, the decreased number of choline acetyltransferase-positive cells in the medial septum was restored by the conditioned medium administration. In conclusion, MSCs-derived conditioned medium may have protective effects of cholinergic neurons in the medial septum, thereby rescuing the cognitive impairment of OBX.
摘要:Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the progressive loss of cognitive functions in affected individuals. Brain tissue pathology is associated with the formation of senile plaques which result from the over-production of amyloid β (Aβ), due to the cleavage of a membrane bound glycoprotein. It is unclear what causes AD and its associated pathologies, but age and genetic predisposition play an import role in the likelihood of disease development. Studies have shown that the reactivation of latent herpes simplex virus 1 (HSV-1) infection can lead to the neuropathy of acute herpes simplex encephalitis (HSE), which causes similar symptoms to AD. HSV-1 infection is a known risk factor for the development of AD, but no study has determined a definitive causal relationship. Using the Qiagen Ingenuity Pathway Analysis (IPA) tool, the inhibitory relationship between therapeutics for AD and HSV-1 were explored. Thirteen drugs developed to decrease Aβ buildup in AD and 32 drugs that act as HSV antivirals were retrieved from the data in the Qiagen Knowledge Base. These drugs were analyzed displayed as two separate networks. While many promising Aβ aggregation-targeting drugs have been discontinued due to lack of efficacy, HSV drugs could serve as potential therapeutics for those with AD. This review aims to describe new insights on how HSV-1 relates to the development of AD and highlight the mechanism of action of Aβ-related drugs and HSV drugs in the context of AD. With HSV-1 being a likely candidate for the causation of AD, there is a need to study the effects of HSV antiviral drugs on those who have AD.
摘要:As the population ages, Alzheimer’s disease is rapidly increasing, and the diagnosis of the disease is still poorly understood. In comparison to cancer, 90% of patients become aware of their diagnosis, but only 45% of the people with Alzheimer’s are aware. Thus, the need for biomarkers for reliable diagnosis is tremendous to help in finding treatment for this serious disease. Hence, the main aim of this paper is to utilize information from baseline measurements to develop a statistical prediction model using multiple logistic regression to distinguish Alzheimer’s disease patients from cognitively normal individuals. Our optimal predictive model includes six risk factors and two interaction terms and has been evaluated using classification accuracy, sensitivity, specificity values and area under the curve.
摘要:Aim: The aim of this study is to highlight the effectiveness of music therapy in Alzheimer’s Disease (AD) and their caregivers. Methods: The biennial 2019 to 2020, 32 patients, with AD (ICD-10), were examined, by a research group composed by a Neurologist, a GP and a Music-psychotherapist. All patients were under pharmaceutical care. The patients’ medical record and musical profile was assessed. The answers were provided by the patients themselves or by their tutors. Then, personal or family sessions were organized with the participation of musical instruments. The patients staging and evaluation were made through MMSE. The test was repeated every six months under the Neurologist’s supervision. Finally, 31 totally patients succeeded to complete our intervention and to be estimated. Results: The duration of follow-up of the patients was 30 months. At the beginning and end of the sessions we obtained the following data: In a total of 32 patients with AD, initially 3 patients (9.37%) had Mild AD, 19 patients (59.37%) had Moderate AD, 10 patients (31.25%) severe AD, based on the MMSE evaluation. After 30 months, 11 patients had Mild AD (35.48%), number resulting from the music benefit of cognitive function in patients with moderate AD. 15 patients with Moderate AD (48.38%) were observed, out of the initial 19 (59.37%) patients with Moderate AD, a number attributed to the sum of patients who improved from severe AD and those who were transferred, benefiting from treatment, from Moderate AD disease to Mild AD. Finally 5 patients with severe AD disease were evaluated (16.12%), while before the treatment we had 10 patients (31.25%) with severe AD. Conclusions: Music therapy is a tool to increase the life quality of the participants. The results expected in the treatment of AD are obtained by means of good collaboration among the research team.
摘要:The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly referred to as COVID-19, brings myriad challenges to research conducted among those more susceptible to the virus. According to the United States (US) Centers for Disease Control (CDC), eight out of ten re-ported COVID-19 deaths are among people > 65 years of age and older. Nonetheless, researchers must continue the crucial work of investigating and understanding diseases that affect the elderly. The focus of this white paper is to assess the challenges associated with research within the elderly population with neurocognitive conditions. Specifically, this paper addresses the need for the standardized administration of performance measures (e.g., neurocognitive assessments) among a dementia population while ensuring the physical safety of participants. Consideration is given to the administration of performance measures and the availability and feasibility of administering these measures remotely to a population that may have difficulty using novel technologies. In implementing remote research assessments, it is suggested that researchers fol-low a GAMMA approach by: 1) establishing clear Guidance on remote visit expectations and processes;2) establishing Appropriate exclusionary criteria in the development of the study design;3) providing subjects Appropriate study Materials for visual processing;4) incorporating Multiple data sources in the overall study design (e.g., caregiver input);and 5) Acknowledging that there will be study limitations as researchers use emerging technology with this patient population, and using mitigation strategies for these limitations where possible.
摘要:The objective of the study was to explore the relationship between the indicators of Alzheimer’s disease and dementia with Lewy bodies using the voxel-based specific regional analysis system for Alzheimer’s Disease (VSRAD) advance. Among 36 patients with suspected dementia, patients with Alzheimer’s disease and dementia with Lewy bodies were identified using VSRAD advance from March 1 to October 30, 2019. All patients underwent brain Magnetic Resonance Imaging (MRI). We diagnosed Alzheimer’s disease using Volume of Interest (VOI) in the Medial Temporal Lobe (MTL) atrophy ratio > 2 and dementia with Lewy bodies using both VOI in the MTL atrophy ratio ≤ 2 and gray/white matter atrophy ratio ≥ 0.2. The correlation between the indicators of Alzheimer’s disease and dementia with Lewy bodies was calculated. The number of patients classified as having Alzheimer’s disease and dementia with Lewy bodies was 25 and 11, respectively. In the Alzheimer’s disease group, the correlation coefficient between the extent of gray matter atrophy and the severity of atrophy in the dorsal brainstem gray matter was r = -0.40 (p = 0.045). In dementia with Lewy bodies group, the correlation coefficient between the extent of gray matter atrophy and the severity of atrophy in the dorsal brainstem white matter was r = -0.78 (p < 0.01). Using VSRAD advance, gray matter atrophy and dorsal brainstem grey/white matter atrophy were found to be negatively correlated in Alzheimer’s disease and dementia with Lewy bodies.
摘要:Despite many decades of researches and large numbers of clinical trials, there remain no effective treatments for Alzheimer’s disease, a major degenerative ageing brain disorder. The potential treatments have focused on targeting the accumulation of amyloid beta-peptide in the brains of patients, but without success in slowing the disease. Many studies have now identified a large range of pathological changes (i.e. altered immune activity, mitochondrial impairment, abnormal microbiome), and links to the external environment (i.e. associations with infections, the influence of air pollution). While the concept of One Health (which considers links between the environment and human disease) has traditionally been applied to the understanding of the human infectious disease, it is argued here that the One Health approach should be adopted for Alzheimer’s disease. This would provide a far more holistic understanding of the disease, and its relationship to a growing number of exogenous factors, as well as could potentially lead to new treatment options targeted at the confluence of external influences, and internal molecular pathways.
摘要:cqvip:Alzheimer’s disease (AD) is a leading cause of death, yet there is no disease-modifying drug therapy currently available. It is critical to establish a diagnosis of AD before clinical system onset so that drug therapies can start earlier. Unfortunately, this is not the current standard practice. Artificial intelligence (AI) holds tremendous promise for identifying AD related structural changes in brain scan images. This paper discusses the recent applications and potential future directions for AI in AD diagnostics. Annual brain scanning and computer vision-assisted early diagnosis is encouraged, so that disease-modifying drug therapy could begin earlier in the progressive pathology.
摘要:As the number of patients with Alzheimer’s disease (AD) continues to rise throughout the twenty- first century, scientists are increasingly looking for remedies, although the cause and pathology of the disease remain uncertain. Among treatments for AD, there is a renewed interest in curcumin as a potential medication. Studies of the substance have found a large amount of consumption associated benefits, including anti-inflammatory and antioxidant effects. Its wide healing properties make it increasingly interesting to scientists, with potential uses in the treatment of cancers, arthritis, various cardiovascular diseases, and neurodegenerative diseases. More recently, curcumin has been shown to have multipotent effects against various symptoms of AD. Among other things, curcumin has been able to ameliorate toxicity of beta-amyloid species, a key part of AD nuerodegeneration, in vivo and in vitro, and has been able to inhibit multiple parts along suspected AD pathology. The goal of this review is to summarize the research done on curcumin with respect to its applicability as a treatment for AD and AD related pathology.
摘要:Background: The Montreal Cognitive Assessment (MoCA) is a useful instrument employed by clinicians to detect cognitive impairment and diagnose probable Alzheimer’s Disease (AD) while in its early stages. Methods: A cross-sectional study was conducted to determine the diagnostic validity of the Philippine version of the MoCA (MoCA-P) among 1385 community-dwelling Filipino elderly from Marikina City, Metro Manila. Results: 509 controls and 97 elderly with probable AD and a Clinical Dementia Rating (CDR) global score of 0.5 were included in the analysis. Analysis of variance showed that the AD group was older (p < 0.05) and had fewer years of education (p < 0.05). The optimal cut-off score to differentiate controls from those with probable AD was 20/21, with a sensitivity of 0.835 and a specificity of 0.723, and area under the curve (AUC) of 0.89 (p < 0.001). The positive and negative likelihood ratios were 3.01 and 0.23, respectively;and pre- and post-test odds were 0.0951 and 0.2224, respectively. Logistic regression showed that the odds of scoring < 20 on the MoCA-P increased with advancing age and with education at ≤7 years (p < 0.05). Two points are added to the MoCA-P score for those with ≤7 years of education. Conclusion: The MoCA-P is a valid instrument for the early detection of mild AD among the Filipino elderly.
摘要:Background: Amnestic mild cognitive impairment (aMCI) and mild-to-moderate Alzheimer’s disease (AD) are clinically distinct but impact cognitive and functional ability similarly. Comprehensive assessment of cognitive and functional deficits may prove useful in informing differential diagnosis in early stages of dementia and in informing endpoint selection in therapeutic AD trials. Objective: The objective of this study was to characterize patterns of cognitive and functional impairment in aMCI and mild-to-moderate AD subjects compared to cognitively intact healthy elderly (HE). Methods: Thirty-one healthy elderly, 20 aMCI and 19 AD participants were administered a cognitive test battery that included the ADAS-Cog and functional assessments. Z-scores were calculated for all endpoints based on the HE reference group. Results: Cognitive deficits were observed in AD and aMCI participants relative to the referent group. On average, aMCI participants performed 1 - 2 standard deviations below HE on cognitive tests, and AD participants performed 2 - 3 standard deviations below HE. Domain-specific functional deficits among AD participants (z- score -0.4 to -6.4) were consistently greater than those of aMCI participants (z-score 0 to -1.7). Conclusion: This study provides further support for comprehensive assessment and monitoring of cognitive and functional domain scores in the diagnosis and treatment of aMCI and mild AD. Domain-specific cognitive scores may be more useful than composite scores in characterizing impairment and decline. Measuring domains such as attention, processing speed and executive function may increase the sensitivity of detecting disease progression and therapeutic effects, particularly in mild-moderate AD where memory decline may be too slow to detect drug effects during a typical clinical trial.
摘要:Alzheimer’s Disease is a complex, progressive condition with symptoms that do not reveal themselves until significant changes to neuronal morphology have already occurred. The delayed manifestation of cognitive decline makes determination of the true etiological origins difficult. As a result, identification of ideal drug targets becomes seemingly impossible. The existing treatments for Alzheimer’s Disease may temporarily suppress the rate of cognitive decline, but do little to slow or halt neuronal decay. While many believe that the current approaches to identifying a cure for the disease are too narrow-minded, focusing heavily on the physical manifestations of the diseased brain such as amyloid plaques and neurofibrillary tangles, this review asserts the status of Alzheimer’s research as rational and multi-faceted.
摘要:Rivastigmine, a dual acetylcholinesterase and butyrylcholinesterase inhibitor, is used for symptomatic treatment of patients with mild to moderately severe dementia in Alzheimer’s disease (AD) patients. In the present study, we found that 5-HT1A receptor (5-HT1AR) is downregulated, whereas 5-HT2A receptor (5-HT2AR) is upregulated in the hippocampal dentate gyrus (DG) and CA1 region by olfactory bulbectomy (OBX) in mice. Furthermore, chronic treatment with rivastigmine (1.0 mg/kg) for 2 weeks starting 2 weeks after OBX operation restored the decreased 5-HT1AR and the increased 5-HT2AR levels. To determine whether cholinergic receptor stimulation by rivastigmine is involved in the rivastigmine-induced regulation of 5-HTR levels, we treated the mice with mecamylamine (2.5 mg/kg), or atropine (5.0 mg/kg) with rivastigmine (1.0 mg/kg) once a day for 2 weeks. Notably, the rivastigmine-induced 5-HT1AR upregulation was eliminated by mecamylamine but not by atropine treatments. On the other hand, the restored 5-HT2AR level by rivastigmine was not affected by either mecamylamine or atropine. Treatment with 8-OH-DPAT, a selective 5-HT1AR agonist improved the decreased 5-HT1AR and the increased 5-HT2AR levels in OBX mice. On the other hand, treatment with TCB-2, a potent 5-HT2AR agonist had no effects on the 5-HT1AR and 5-HT2AR dysregulation in OBX mice. Taken together, nicotinic acetylcholine receptor (nAChR) stimulation mediates rivastigmine-induced upregulation of 5-HT1AR. Therefore, we speculate that the increased ACh levels by rivastigmine can stimulate nAChR located on serotonergic nerve terminals and stimulate 5-HT1AR by the enhanced 5-HT release in the hippocampus. The 5-HT1AR stimulation likely mediates the improvement of 5-HT1AR levels as auto-receptor in OBX hippocampus.
摘要:To date, therapies to prevent or treat Alzheimer’s disease (AD) have largely focused on removing excess aggregation-prone amyloid peptide Aβ from the brain, an approach that has produced disappointing clinical outcomes. An alternative hypothesis proposes that Aβ production and aggregation is a symptom of a larger, systemic disease affecting the regulation of lipids, including cholesterol. In this scenario, lipid dysregulation would likely occur early in the disease process, making it an ideal target for predicting risk of mild cognitive impairment (MCI) to AD conversion. Here, we report that levels of filipin, a fluorescent polyene macrolide widely used as a diagnostic tool for diseases of lipid dysregulation, correlate with cellular damage caused by 27-hydroxycholesterol and with dementia status in human peripheral blood cells. These results provide strong preliminary data suggesting that filipin could be of use in the development of a quick and inexpensive method to measure the risk of AD conversion in patients with MCI, supplementing existing testing strategies that focus on the consequences of Aβ accumulation.
摘要:Neuropathologically, Alzheimer’s disease is characterized by the presence of extracellular deposits of amyloid-β peptides, intracellular neurofibrillary tangles and atrophy of the basal forebrain cholinergic neurons. The research of pathogenesis of Alzheimer’s disease inspirits potential clinical drugs for treatment. To block the progression of the disease, drugs under development have to interfere with the pathogenic steps responsible for the clinical symptoms, including cholinergic deficit, calcium dysregulation, inflammation and oxidative damage, and the deposition of amyloid- β plaques and of neurofibrillary tangles. In this review, the pertinent literature about drugs targeted on relieving symptoms above is reviewed. We aim to discuss possible research priorities in the future.
摘要:Mild cognitive impairment is sometimes regarded as related to aging. However, statistically every second case turns into full dementia, which still is resistant to any treatment. It is therefore desir-able to recognize deviations from normality as early as possible. This might be feasible by using quantitative EEG analysis in the presence of mental work. The present retrospective data analysis revealed a new quantitative biomarker indicating the degree of impairment. Current source density was calculated from 16 channel EEG using CATEEM?? software. Four different conditions were analyzed: relaxed state, performing a d2-concentration test, a calculation performance test and a memory test for 5 min each. Subjects older than 40 years were divided into two groups according to their DemTect score: 13 - 18 (HC;n = 44) or 8 - 12 (MCI;n = 45). Spectral power was chopped into six frequency ranges (delta, theta, alpha 1, alpha 2, beta 1 and beta 2). Average spectral power was enhanced in the MCI group in comparison to healthy subjects with respect to delta (p = 0.05) during relaxed state when all electrode positions were regarded. With respect to EEG recording during performance of three different psychometric tests it was recognized that mainly spectral changes during performance of the d2-concentration test were related to mild cognitive impairment. With regard to all electrode positions statistically significantly lower spectral power values were reached during the d2-test for delta (p = 0.001), theta (p = 0.0001) and alpha 1 waves (p = 0.08) in impaired subjects in comparison to healthy subjects. Regarding regions of interest increases of delta and theta power were seen in the fronto-temporal brain during performance of the d2-concentration test. These increases disappeared when looking at MCI data. In the centro-parietal region decreases of alpha and beta 1 power emerged, which were even larger in MCI subjects. No MCI-dependent changes were observed in the other two tests. A correlation was found between psychometric performance of the d2-test and the DemTect score (r = 0.51). MCI subjects had statistically significant worse performance in all three mental challenges in comparison to healthy volunteers. It is concluded that MCI can be characterized at an early stage by EEG recording in the relaxed state. High spectral delta and theta power in general and specifically at fronto- temporal electrode positions (especially at T3) was recognized as a biomarker for MCI. A DemTect score of 8-12 was validated as indicative for MCI.
摘要:Chronic neuroinflammation is thought to play an etiological role in Alzheimer’s disease (AD) which is characterized pathologically by amyloid and tau formation, as well as neuritic dystrophy and synaptic degeneration. The causal relationship between these pathological events is a topic of ongoing research and discussion. Recent data from transgenic AD models point to a tight spatio-temporal link between neuritic and amyloid pathology, with the obligatory enzyme for β-amyloid (Aβ) production, namely β-secretase-1 (BACE1), being overexpressed in axon terminals undergoing dystrophic change. However, the axonal pathology inherent with BACE1 elevation seen in transgenic AD mice may be secondary to increased soluble Aβ in these genetically modified animals. Further, it is unclear whether the inflammation seen in AD is the result of , or the cause of neuritic dystrophy. Here we explored the occurrence of AD-like axonal and dendritic pathology in adult rat brains affected by LPS-induced chronic neuroinflammation. Unilateral intracerebral LPS injection induced prominent inflammatory response in glial cells in the ipsilateral cortex and hippocampal formation. BACE1 protein levels were elevated in the ipsilateral hippocampal lysates in the LPS-treated animals relative to controls. BACE1 immunoreactive dystrophic axons appeared in the LPS-treated ipsilateral cortex and hippocampal formation, colocalizing with increased β-amyloid precursor protein and Aβ antibody (4G8) immunolabeling. Quantitative Golgi studies revealed reduction of dendritic branching points and spine density on cortical layer III and hippocampal CA3 pyramidal neurons in the LPS-treated ipsilateral cerebrum. These findings suggest that Alzheimer-like amyloidogenic axonal pathology and dendritic degeneration occur in wildtype mammalian brain in partnership with neuroinflammation following LPS injection.
摘要:Introduction: Dementia constitutes a public health hazard in developing countries. There is little data in the sub-Saharan region of African especially in Benin. Objective: Determining dementia hospitalization prevalence and identifying its associated factors in CNHU-HKM, Cotonou. Method: It was a cross-sectional, prospective, descriptive and analytical research conducted from October 2012 to July 2013 in the neurology department;it involved 251 patients aged 50 and above. Dementia screening was conducted using a modified and adapted Mini Mental Scale Examination (MMSE). Dementia clinical and etiological diagnoses were respectively conducted based on DMS-IV and HACHINSKI criteria. Results: Patients were averagely aged 60.9 ± 8.1. Sex ratio (Male/Female) was 1.07. Dementia prevalence was 8.8%. This rate increased proportionally with age, from 5.3% with patients aged below 60 to 12.7% with patients aged above 60. Degenerative dementia was the most predominant type (50%). Following multi-varied analysis, smoking (RC = 6.05 [IC 95% = 1.26 - 29.38] p = 0.0001) and stroke past records (RC = 6.05 [IC 95% = 1.26 - 29.38] p = 0.001) revealed to be the factors associated with dementia. Conclusion: This research showed that dementia affects a significant part of the aging population in CNHU-HKM. It is imperative to combat its associated factors so as to defuse its prevalence.
摘要:Background: Many instruments used to assess outcomes of treatment for Alzheimer’s disease (AD) have no published evidence of their relevance and content validity in earlier stages of the disease, i.e., mild cognitive impairment, or prodromal AD (pAD). The objective of this project was to evaluate the applicability and usefulness of the Perceived Deficits Questionnaire (PDQ) as an outcome measure in this population using qualitative methodology to support content validity. Method: Two waves of qualitative interviews were conducted in patients with MCI and pAD. Results: Evidence for content validity and usefulness of the instrument was demonstrated in the patient interviews. Minor modifications to the wording of several items were suggested for the PDQ and the recall period was changed. Conclusion: With these modifications, the PDQ has improved content validity and relevance. It is therefore a potentially useful outcome measure to evaluate therapeutic benefit in interventional studies of patients in the early stages of AD.
摘要:There are no data available on the prevalence of Mild Cognitive Impairment (MCI) in Greece, and the existing information about dementia shows important variations depending on the geographical setting as well as the methodology employed. The aim of this study was to determine the prevalence of MCI in individuals aged over 65 in a rural area in the north part of Greece. From 1428 residents, 678 were finally examined, with a mean age of 73.35 years. Assessments, including neuropsychological testing, neurological examination and medical history, were used to assign a diagnosis of normal cognition, mild cognitive impairment (MCI), with or without depression, depression or dementia according to suitable criteria. A questionnaire was also used to obtain social and demographic data. The 26.3% were classified as Mild Cognitive Impaired without depression, the 8.8% as Mild Cognitive Impaired due to depression, 5.9% had sole depression, the 2.4% were diagnosed with dementia and 56.6% had normal mental status. The observed prevalence for MCI with and without depression implies a total of 35.1% of all people aged over 65 with MCI in the study area. Mild cognitive impairment is more prevalent in Greece than dementia, and its subtypes vary in prevalence.
摘要:The study was performed to examine and assess the impact of the education, occupation and leisure time on building brain and cognitive reserves (CBR). A cross sectional study of 132 persons at age between 40 to 70 years old has been conducted. A structured questionnaire covering multiple constructs was used to collect the data. Multivariate regression results show that the three independent variables (LE, OC and ED) were statistically significant in the models with CBR as dependent variable. Leisure time and activities (LE) make the strongest unique contribution (0.683) followed by occupation (0.261) and the weak contribution of the education (0.198) to explain the dependent variable cognitive and brain reserve (CBR). The Brain and Cognitive Reserve hypothesesassumes that a rich intellectual measures and abilities a person have during her/his life enable this person to cope with difficult cognitive tasks and social events in life.
摘要:Understanding the signaling cascade that leads to the rapid memory and cognitive breakdown in Alzheimer’s disease is the key to finding a potential treatment method for the disease. Recently, Larson et al. connect the roles of major proteins implicated in the disease progression and propose targeting of cellular prion protein (PrPc) as a way of someday rescuing synaptic plasticity in humans with Alzheimer’s, as it has been done on mice.
摘要:Background: Many studies have underlined as caregiving for people with Alzheimer’s disease (AD) is highly stressful and has significant negative consequences. Objectives: The study of the structure of personality, can help to understand the association between depression, intrapsychic and interpersonal processes of caregivers of Alzheimer’s disease patients and what kind of intervention can be planned to favor the stress burden management. Methods: Case group: Caregivers (CG) (n = 75);control group, Subjects not Caregivers (nCG) (n. 104). Tests: SASB questionnaire (Structural Analysis of Interpersonal Behavior) describing intrapsychic and interpersonal processes of the structure of personality validated on the basis of DSMIV;CDQ questionnaires—depression. Results: Intrapsychic level: From the results it emerged that CGs had lower autonomy in their choices, and lower acceptance of their own feelings, and exercised greater self-control exhausting themselves toward predetermined goals, and more depression compared to the control group. They may be not able to achieve psychic equilibrium in the presence of stress: they may likely become disoriented and engage in behaviors that may be self-defeating. SASB-Cl = Autonomy (p 0.001);SASB-Cl2-Autonomy and Love (p 0.001), SASB-CL3-Love (p 0.001);SASB-Cl4 Love and control (p 0.001), SASB-CL5-Control (p = 0.015), SASB-Cl6-Control and hate (p 0.001), SASB-Cl7-Hate (p Conclusions: Intrapsychic characteristics such as tendency to depression, inability to being in contact with their own feelings, excessive self-control may be linked to difficulties in facing burden of care and indicate serious difficulties to adaptation to burden condition. The knowledge of these modalities could allow to plan a psychotherapeutic and multidisciplinary intervention aimed at facing and overcoming the psychological distress of the caregiver.
摘要:Alzheimer’s disease (AD) is a slowly progressive, neurodegenerative disorder with an insidious onset that is characterized by severe decline in memory, thinking and reasoning skills. Advanced age is a prominent risk factor for AD and other metabolic diseases, such as type II diabetes and atherosclerosis. Their causal mechanisms are multifaceted and not fully understood. The precise pathophysiology of AD remains a mystery despite decades of intensive investigation. Thus far, there is no truly successful AD therapy. Arginase is the central enzyme of the urea cycle. Recent studies have identified arginase function in the brain and associated this enzyme with the development of neurodegenerative diseases. Upregulation of arginase has been shown to contribute to endothelial dysfunction, ischemia-reperfusion, atherosclerosis, diabetes, and neurodegeneration. Other state-of-the-art discoveries of the precise molecular machinery of neurodegeneration have provided new directions for the rational development of innovative therapeutic strategies in the treatment of common neurodegenerative diseases. In this context, the regulation of arginase activity appears to be a universal approach in interfering with the pathogenesis of AD and providing relief for it and other metabolic disorders. Therefore, the enzyme represents a novel therapeutic target. Arginase inhibition has been shown to reverse amyloid-driven neuronal dysfunction and microgliosis and prevent the development of other AD symptoms in rodent models of AD. Consequently, the methodology represents a promising direction for clinical development.
摘要:Alzheimer’s disease (AD) leads to the generation of β-amyloid (Aβ), which may damage DNA and thus lead to apoptosis induction by the p53 pathway. Dysfunction of the p53 protein may then be connected with the development of AD. Studies were conducted on 28 AD patients and 30 non-AD controls. Analysis of TP53 mutations in exon 7 was performed on DNA isolated from whole blood and biochemical parameters in the peripheral lymphocytes of these individuals. Our study showed a silent mutation TP53 C708T (21%) [p TP53 C748A (4%) only in the AD patients. Moreover, in AD patients with the TP53 C748A mutation, the level of 8-oxo-2’- deoxyguanosine (8-oxo2dG) was more than 5 times higher than the average level in this study group. In AD patients with the wild-type TP53 gene, the level of 8-oxo2dG was correlated with the level of protein p53 (R = +0.7388, p TP53 (p TP53 (C748A, C708T) may be associated with pathogenesis of AD.
摘要:The phenomenon of early-onset dementia remains an under-researched subject from the perspective of health care professionals. The aim of this qualitative study was to document the experiences and service needs of patients and their family caregivers for optimal clinical management of early-onset dementia from the perspective of health care professionals. A sample of 13 health care professionals from various disciplines, who worked with individuals who suffered from Alzheimer’s disease or related disorders and their family caregivers, took part in focus groups or semi-structured individual interviews, based on a life course perspective. Three recurrent themes emerged from the data collected from health care professionals and are related to: 1) identification with the difficult experiences of caregivers and powerlessness in view of the lack of services;2) gaps in the care and services offered, including the lack of clinical tools to ensure that patients under age 65 were diagnosed and received follow-up care, and 3) solutions for care and services that were tailored to the needs of the caregiver-patient dyads and health care professionals, the most important being that the residual abilities of younger patients be taken into account, that flexible forms of respite be offered to family caregivers and that training be provided to health care professionals. The results of this study provided some innovative guidelines for optimal clinical management of early-onset dementia in terms of the caregiver-patient dyad.
阿尔茨海默氏病研究进展(英文)的期刊信息
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