International Journal of Alzheimer's Disease最新文献

Alzheimer's disease is first characterised by memory loss related to the central cholinergic system alteration. Available drugs provide symptomatic treatment with known side effects. The present study is aimed to evaluate the properties of Carissa edulis aqueous extract on a Scopolamine mouse model as an attempt to search for new compounds against Alzheimer's disease-related memory impairment. Memory impairment was induced by administration of 1 mg/kg (i.p.) of Scopolamine for 7 days, and mice were treated with Carissa edulis aqueous extract. Behavioural studies were performed using T-maze and novel object recognition task for assessing learning and memory and open field test for locomotion. Brain acetylcholinesterase enzyme (AChE) activity was measured to evaluate the central cholinergic system. The level of MDA, glutathione, and catalase activity were measured to evaluate the oxidative stress level. Administration of Scopolamine shows a decrease in learning and memory enhancement during behavioural studies. A significant decrease in the time spent in the preferred arm of T-maze, in the time spent in the exploration of the novel object, and in the discrimination index of the familiar object was also observed. The significant impairment of the central cholinergic system was characterised in mice by an increase of AChE activity to 2.55 ± 0.10 mol/min/g with an increase in oxidative stress. Treatment with the different doses of Carissa edulis (62.8, 157, 314, and 628 mg/kg orally administrated) significantly increased the memory of mice in T-maze and novel object recognition tests and also ameliorated locomotion of mice in the open field. Carissa edulis aqueous extract treatment also decreases the AChE activity and brain oxidative stress. It is concluded that administration of Carissa edulis aqueous extract enhances memory of mice by reducing AChE activity and demonstrating antioxidant properties. This could be developed into a novel therapy against memory impairment related to Alzheimer's disease.

Human clinical trials seek to ameliorate the disease states and symptomatic progression of illnesses that, as of yet, are largely untreatable according to clinical standards. Ideally, clinical trials test "disease-modifying drugs," i.e., therapeutic agents that specifically modify pathological features or molecular bases of the disease and would presumably have a large impact on disease progression. In the case of Alzheimer's disease (AD), however, this approach appears to have stalled progress in the successful development of clinically useful therapies. For the last 25 years, clinical trials involving AD have centered on beta-amyloid (Aβ) and the Aβ hypothesis of AD progression and pathology. According to this hypothesis, the progression of AD begins following an accumulation of Aβ peptide, leading to eventual synapse loss and neuronal cell death: the true overriding pathological feature of AD. Clinical trials arising from the Aβ hypothesis target causal steps in the pathway in order to reduce the formation of Aβ or enhance clearance, and though agents have been successful in this aim, they remain unsuccessful in rescuing cognitive function or slowing cognitive decline. As such, further use of resources in the development of treatment options for AD that target Aβ, its precursors, or its products should be reevaluated. The purpose of this review was to give an overview of how human clinical trials are conducted in the USA and to assess the results of recent failed trials involving AD, the majority of which were based on the Aβ hypothesis. Based on these current findings, it is suggested that lowering Aβ is an unproven strategy, and it may be time to refocus on other targets for the treatment of this disease including pathological forms of tau.

Cognitive impairment (CI) is among the leading causes of disability in humans. It is estimated that over 35.6 million people are suffering from Alzheimer's disease- (AD-) associated cognitive deficits globally with these statistics projected to rise over 115.4 million by the year 2050. There is no specific etiology for this cognitive impairment; however, various contributing factors including advancing age (>60 years old), oxidative stress, cerebral injuries, infections, neurologic disorders, and cancer have been implicated. Despite various attempts to manage CI, no curative medicines are yet available. The current drugs used to manage symptoms of AD-associated CI including Donepezil and Rivastigmine among others are only palliative rather than therapeutic. Furthermore, these agents have been associated with undesirable side effects. This calls for alternative and complementary approaches aimed at either preventing or reverting AD-related CI in a curative way without causing adverse events. It is estimated that over 80% of the world's population utilize herbal medicines for basic healthcare as it is considered safe, affordable, and easily accessible as opposed to conventional healthcare. Various parts of P. thonningii are used in traditional medicine to manage various conditions including CI. However, empirical and scientific data to validate these uses is lacking. In this study, the Morris water maze (MWM) experiment was adopted to evaluate the cognitive-enhancing effects of the studied plant extracts. The malondialdehyde (MDA) profiles in the brains of experimental mice were determined using the thiobarbituric acid reactive substances (TBARS) test. Moreover, qualitative phytochemical profiling of the studied plant extracts was performed using standard procedures. The results showed remarkable cognitive-enhancing activities which were reflected in significantly shorter transfer latencies, navigation distances, longer time spent in platform quadrant, and lower MDA levels compared with those recorded for the negative control mice (p < 0.05). Phytochemical screening of the studied plant extracts revealed the presence of antioxidant phytocompounds, which may have played key roles in the extracts' potency. Based on the findings herein, P. thonningii extracts, especially the aqueous ones have a promising potential for the management of AD-associated CI. Further studies aimed at isolating and characterizing specific active compounds for CI from P. thonningii are recommended. Additionally, specific mode(s) of action of active principles should be elucidated. Moreover, toxicity studies should be done on the studied plant extracts to ascertain their safety.

Because the interpersonal skills of individuals with dementia often decline, family members may question their own ability to interact meaningfully. These family members may experience fear of incompetence (i.e., fear of being unable to relate in a meaningful way or take care of a close family member with dementia). Thus, the goal of this research was to develop, refine, and psychometrically validate a scale (Fear of Incompetence-Dementia Scale; FOI-D) assessing fear of incompetence in the context of relationships with a close family member diagnosed with dementia. Three online studies were conducted to accomplish the primary objective. In Study One, the factor structure of the FOI-D was assessed by conducting an exploratory factor analysis using data from 710 adults who indicated having a close living family member who had been diagnosed with dementia. In Study Two, the factor structure was validated via a confirmatory factor analysis and the psychometric properties were established using data from 636 adults who had a family member with dementia. Finally, Study Three determined the temporal consistency of the scale by retesting 58 participants from Study Two. The results from Study One indicated that the FOI-D Scale accounted for 51.75% of the variance and was comprised of three subscales: the Interaction Concerns subscale, the Caregiving Concerns subscale, and the Knowledge Concerns subscale. In Study Two, the three-factor structure was supported, resulting in a 58-item scale. Investigation of the psychometric properties demonstrated the FOI-D to be reliable and valid. In Study Three, the FOI-D Scale demonstrated excellent temporal consistency. This research provides future investigators, educators, and practitioners with an adaptable comprehensive tool assessing fear of incompetence in a variety of settings.

Introduction: Alzheimer's, a neurodegenerative disease, is becoming a growing burden and the leading cause of disability among older people, and there is no cure for it. It is set to be the biggest killer among the growing elderly population. The aim of this study was to assess the knowledge of Alzheimer's disease among college students in Kathmandu metropolitan city.

Methods: This was a descriptive cross-sectional study among 385 randomly selected bachelor students of Kathmandu metropolitan city. The questionnaire included 2 sections. Section I addressed the sociodemographic characteristics of the participants. Section II addressed or covered the Alzheimer's Disease Knowledge Scale (ADKS) test. ADKS contains a set of 30 items, with true and false options. 1 point was given for the correct answer and 0 for the incorrect answer. The final sum was then the total score of the participant. Frequency, percentage, mean, and standard deviation were calculated, and the chi-square test was used to measure the association between two categorical variables.

Results: The mean ADKS (Alzheimer's Disease Knowledge Scale) score is 15.45 ± 2.95 with the lowest and highest mean total scores of 8 and 26, respectively. 49.5% of the respondents scored above the mean. The number of male and female respondents who scored above the mean is 68 and 95, respectively, with p value 0.71 and odds ratio 0.922. There is no association between gender and knowledge level. Gender seemed to have no effect on the knowledge about Alzheimer's disease on the basis of the Alzheimer's Disease Knowledge Scale (ADKS). However, science students had comparatively better knowledge about disease than management students. The mean score of science and management is 15.9 and 15.04, respectively, with p value 0.004. There is association between knowledge score and faculty.

Conclusion: This study concluded that the knowledge level of college students on Alzheimer's disease is below moderate. The findings concluded that there is association between faculty and knowledge score.

Prior studies have identified numerous barriers to the prompt diagnosis of patients with suspected Alzheimer's disease (AD). The aim of the study was to evaluate physician's perceptions of the importance of previously identified barriers to diagnosis, but with a specific focus on the presentation of mild cognitive impairment (MCI), which may be indicative of neurodegenerative disorders such as AD. A second aim was to evaluate how the perspective of primary care physicians (PCPs) may differ from that of specialists. A cross-sectional online survey of PCPs and specialists who routinely manage patients with complaints of age-related cognitive impairment was conducted. Participants were asked to identify barriers to prompt diagnosis from prespecified lists of known diagnostic challenges categorized into 4 domains: patient-related, physician-related, setting-related, and those relating to the clinical profile of AD. Physicians report a range of barriers when attempting to diagnose MCI and AD. Major themes included patients seeing cognitive decline as a normal part of aging and not disclosing symptoms, long waiting lists, and a lack of treatment options and definitive biomarker tests. Generally, PCPs and specialists showed broad agreement; however, PCPs were more likely to identify burdens on the healthcare system, such as long waiting lists and inadequate time to evaluate patients. Substantial barriers continue to hinder early diagnosis of MCI and AD. There are numerous areas where improvements might be made but the implementation of potential interventions will likely be associated with financial strain for many healthcare systems.

Alzheimer's disease (AD), the most common cause of sporadic dementia of in adults, shows increased risk of occurrence with aging and is destined to become a major sociomedical tragedy over the next few decades. Although likely complex in origin, sporadic AD is characterized by a progressive and stereotyped neuropathology with aggregated protein deposition (esp beta amyloid (BA) and hyperphosphorylated tau (P-tau)) and neuronal degeneration. To date, prevention of BA synthesis or immune-mediated removal of BA has failed to alter AD progression. Development and testing of P-tau therapeutics are a work in progress. AD brain tissues show multiple system deficits, including loss of respiratory capacity. In the present study there were no differences in mitochondrial mass between AD and CTL samples. We examined mitochondrial preparations of postmortem AD and CTL frontal cortex for relative levels of individual respiratory protein complexes by Western immunoblotting. ANOVA revealed deficiencies of all respiratory complex subunits in AD; post-ANOVA t-testing revealed significant differences in levels of subunits for complexes II, III, and V, borderline significance for subunit of complex IV, and no difference for subunit of complex I. We also examined mitochondrial extracts with blue-native gel electrophoresis combined with immunoblotting for subunits of complexes I and III to search for "respiratory supercomplexes" (RSC's). We found that levels of RSC's did not differ between AD and CTL samples. Mitochondrial preparations from end-stage AD brain tissue showed loss of individual ATP-producing respiration subunits but preservation of levels of assembled respiratory subunits into RSC's. Possible explanations include insufficient sensitivity of our method of RSC detection to find loss of individual subunits, or normal levels of RSC's in AD brain mitochondria coupled with decreased levels of nonassembled respiratory complex subunits. Disease-altering therapies of early AD could include stimulation of mitochondrial biogenesis to overcome loss of respiratory subunits.

The diagnostic process for patients presenting with cognitive decline and suspected dementia is complex. Physicians face challenges distinguishing between normal aging, mild cognitive impairment, Alzheimer's disease, and other dementias. Although there is some evidence for improving attitudes towards the importance of prompt diagnosis, there is limited information describing how physicians approach this diagnostic challenge in practice. This was explored in the present study. Across-sectional survey of primary care and specialist physicians, in 5 European countries, Canada, and the United States, was conducted. Participants were asked about their use of cognitive screening tools and diagnostic technologies, as well as the rationales and barriers for use. In total, 1365 physicians participated in the survey, 63% of whom were specialists. Most physicians stated they use objective cognitive tools to aid the early detection of suspected mild cognitive impairment or Alzheimer's disease in patients. The Mini-Mental State Examination was the most common tool used for initial screening; respondents cited speed and ease of use but noted its lack of specificity. Cerebrospinal fluid biomarker and amyloid positron emission tomography tests, respectively, had been used by only 26% and 32% of physicians in the preceding 6 months, although patterns of use varied across countries. The most commonly cited reasons for not ordering such tests were invasiveness (for cerebrospinal fluid biomarker testing) and cost (for amyloid positron emission tomography imaging). Data reported by physicians reveal differences in the approaches to the diagnostics process in Alzheimer's. A higher proportion of primary care physicians in the United States are routinely incorporating cognitive assessment tools into annual visits, but this is due to country differences in clinical practice. The value of screening tools and regular use could be discussed further with physicians; however, lack of specificity associated with cognitive tools and the investment required from patients and the healthcare system are limiting factors.

Aim of the paper is to quantify effects of socioeconomic factors on Alzheimer's Disease Mortality in the Slovak Republic. We applied potential gains in life expectancy (PGLE) method to measure the impact of elimination of Alzheimer's disease on life expectance in Slovak regions. PGLE is based on life table adjustment according to elimination of mortality caused by specific diagnosis. Our dataset consists of all deceased from Slovak Republic from 2001 to 2015. We analyse the impact of unemployment rate, GDP per capita, average wage, and education on life expectance in Slovak regions. To estimate that impact, ordinary least squares (OLS) is applied. According to our model, gross domestic product, average wage, and education influence mortality caused by Alzheimer's disease.