International Journal of Alzheimer's Disease最新文献

{"title":"Cholesterol and copper affect learning and memory in the rabbit.","authors":"Bernard G Schreurs","doi":"10.1155/2013/518780","DOIUrl":"https://doi.org/10.1155/2013/518780","url":null,"abstract":"<p><p>A rabbit model of Alzheimer's disease based on feeding a cholesterol diet for eight weeks shows sixteen hallmarks of the disease including beta amyloid accumulation and learning and memory changes. Although we have shown that feeding 2% cholesterol and adding copper to the drinking water can retard learning, other studies have shown that feeding dietary cholesterol before learning can improve acquisition and feeding cholesterol after learning can degrade long-term memory. We explore the development of this model, the issues surrounding the role of copper, and the particular contributions of the late D. Larry Sparks. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"518780"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/518780","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31764130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroinflammation and copper in Alzheimer's disease.","authors":"Xin Yi Choo,&nbsp;Lobna Alukaidey,&nbsp;Anthony R White,&nbsp;Alexandra Grubman","doi":"10.1155/2013/145345","DOIUrl":"https://doi.org/10.1155/2013/145345","url":null,"abstract":"<p><p>Inflammation is the innate immune response to infection or tissue damage. Initiation of proinflammatory cascades in the central nervous system (CNS) occurs through recognition of danger associated molecular patterns by cognate immune receptors expressed on inflammatory cells and leads to rapid responses to remove the danger stimulus. The presence of activated microglia and astrocytes in the vicinity of amyloid plaques in the brains of Alzheimer's disease (AD) patients and mouse models implicates inflammation as a contributor to AD pathogenesis. Activated microglia play a critical role in amyloid clearance, but chronic deregulation of CNS inflammatory pathways results in secretion of neurotoxic mediators that ultimately contribute to neurodegeneration in AD. Copper (Cu) homeostasis is profoundly affected in AD, and accumulated extracellular Cu drives A β aggregation, while intracellular Cu deficiency limits bioavailable Cu required for CNS functions. This review presents an overview of inflammatory events that occur in AD in response to A β and highlights recent advances on the role of Cu in modulation of beneficial and detrimental inflammatory responses in AD. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"145345"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/145345","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31982320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensorimotor Cortex Reorganization in Alzheimer's Disease and Metal Dysfunction: A MEG Study.","authors":"C Salustri,&nbsp;F Tecchio,&nbsp;F Zappasodi,&nbsp;L Tomasevic,&nbsp;M Ercolani,&nbsp;F Moffa,&nbsp;E Cassetta,&nbsp;P M Rossini,&nbsp;R Squitti","doi":"10.1155/2013/638312","DOIUrl":"https://doi.org/10.1155/2013/638312","url":null,"abstract":"<p><p>Objective. To verify whether systemic biometals dysfunctions affect neurotransmission in living Alzheimer's disease (AD) patients. Methods. We performed a case-control study using magnetoencephalography to detect sensorimotor fields of AD patients, at rest and during median nerve stimulation. We analyzed position and amount of neurons synchronously activated by the stimulation in both hemispheres to investigate the capability of the primary somatosensory cortex to reorganize its circuitry disrupted by the disease. We also assessed systemic levels of copper, ceruloplasmin, non-Cp copper (i.e., copper not bound to ceruloplasmin), peroxides, transferrin, and total antioxidant capacity. Results. Patients' sensorimotor generators appeared spatially shifted, despite no change of latency and strength, while spontaneous activity sources appeared unchanged. Neuronal reorganization was greater in moderately ill patients, while delta activity increased in severe patients. Non-Cp copper was the only biological variable appearing to be associated with patient sensorimotor transmission. Conclusions. Our data strengthen the notion that non-Cp copper, not copper in general, affects neuronal activity in AD. Significance. High plasticity in the disease early stages in regions controlling more commonly used body parts strengthens the notion that physical and cognitive activities are protective factors against progression of dementia. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"638312"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/638312","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32022317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Beta-amyloid protein of Alzheimer's disease: communication breakdown by modifying the neuronal cytoskeleton.","authors":"Sara H Mokhtar,&nbsp;Maha M Bakhuraysah,&nbsp;David S Cram,&nbsp;Steven Petratos","doi":"10.1155/2013/910502","DOIUrl":"https://doi.org/10.1155/2013/910502","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is one of the most prevalent severe neurological disorders afflicting our aged population. Cognitive decline, a major symptom exhibited by AD patients, is associated with neuritic dystrophy, a degenerative growth state of neurites. The molecular mechanisms governing neuritic dystrophy remain unclear. Mounting evidence indicates that the AD-causative agent, β -amyloid protein (A β ), induces neuritic dystrophy. Indeed, neuritic dystrophy is commonly found decorating A β -rich amyloid plaques (APs) in the AD brain. Furthermore, disruption and degeneration of the neuronal microtubule system in neurons forming dystrophic neurites may occur as a consequence of A β -mediated downstream signaling. This review defines potential molecular pathways, which may be modulated subsequent to A β -dependent interactions with the neuronal membrane as a consequence of increasing amyloid burden in the brain. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"910502"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/910502","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32022318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Care for Alzheimer's disease.","authors":"Hiroyuki Umegaki,&nbsp;Hajime Takechi,&nbsp;Hiroko H Dodge","doi":"10.1155/2013/516852","DOIUrl":"https://doi.org/10.1155/2013/516852","url":null,"abstract":"Cognitive impairment due to dementia deprives those afflicted with the disease of their autonomy and ability to take care of themselves, making them dependent on care provided by formal and informal resources. Moreover, as the disease progresses, behavioral and psychological symptoms of dementia (BPSD) may occur. BPSD are often troublesome to both caregivers and the patients themselves. The care burden is often heavy and disrupts the lives of family members surrounding the patient. \u0000 \u0000Early screening and identification of cognitive decline will help those with the disease and family members prepare for better care and may reduce the patients' BPSD. Effective screening for dementia, which can be administered at ambulatory care facilities, is warranted. Vascular risk factors, especially type 2 diabetes mellitus, have been found to increase the risk of developing Alzheimer's disease (AD). The prevalence of type 2 diabetes mellitus is increasing in Japan. In this special issue, T. Matsuzawa et al. describe an index for screening for mild or moderate AD cases among the elderly with type 2 diabetes mellitus. The index includes self-reported answers to a questionnaire regarding subjective memory complaints and daily functioning and information on vascular risk factors obtained from clinical charts. The index had satisfactory discriminatory ability to identify those with AD among patients with diabetes. This may contribute to an effective screening for AD among those with diabetes, that is, known high-risk populations. \u0000 \u0000Current treatments for AD are limited to alleviating symptoms, but not reversing the pathological progress. Pharmacological treatments for BPSD, which are critical for the well-being of both patients and caregivers, are also limited in their effectiveness. The study by H. Fukui et al. examines changes in sex hormones associated with the pathogenesis of AD before and after music therapy among patients with AD. They show that music therapy modified the secretion of sex hormones, and the results also suggest that problematic behavior may be reduced this way. The therapy has the potential to become a safe alternative treatment that is as effective as hormone replacement, but with fewer side effects. The underlying biological mechanism of effects shown in this study is convincing and a welcome addition to the field. \u0000 \u0000The number of those suffering from dementia is increasing worldwide. Effective caregiving strategies and targeted care management programs are urgently needed to enhance the well-being of those with AD and their caregivers. T. Passos et al. examined the met and unmet needs of the elderly with mental health problems and their care in Portugal. The main unmet needs identified were daytime activities, social benefits, company, psychological distress, and incontinence. Some of these unmet needs may be universal across countries worldwide, but others may differ depending on specific health care systems and cultures. A comparison wi","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"516852"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/516852","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31458640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of the mini-cog for detection of cognitive impairment in primary care: data from two spanish studies.","authors":"Cristóbal Carnero-Pardo,&nbsp;Isabel Cruz-Orduña,&nbsp;Beatriz Espejo-Martínez,&nbsp;Carolina Martos-Aparicio,&nbsp;Samuel López-Alcalde,&nbsp;Javier Olazarán","doi":"10.1155/2013/285462","DOIUrl":"https://doi.org/10.1155/2013/285462","url":null,"abstract":"<p><p>Objectives. To study the utility of the Mini-Cog test for detection of patients with cognitive impairment (CI) in primary care (PC). Methods. We pooled data from two phase III studies conducted in Spain. Patients with complaints or suspicion of CI were consecutively recruited by PC physicians. The cognitive diagnosis was performed by an expert neurologist, after formal neuropsychological evaluation. The Mini-Cog score was calculated post hoc, and its diagnostic utility was evaluated and compared with the utility of the Mini-Mental State (MMS), the Clock Drawing Test (CDT), and the sum of the MMS and the CDT (MMS + CDT) using the area under the receiver operating characteristic curve (AUC). The best cut points were obtained on the basis of diagnostic accuracy (DA) and kappa index. Results. A total sample of 307 subjects (176 CI) was analyzed. The Mini-Cog displayed an AUC (±SE) of 0.78 ± 0.02, which was significantly inferior to the AUC of the CDT (0.84 ± 0.02), the MMS (0.84 ± 0.02), and the MMS + CDT (0.86 ± 0.02). The best cut point of the Mini-Cog was 1/2 (sensitivity 0.60, specificity 0.90, DA 0.73, and kappa index 0.48 ± 0.05). Conclusions. The utility of the Mini-Cog for detection of CI in PC was very modest, clearly inferior to the MMS or the CDT. These results do not permit recommendation of the Mini-Cog in PC. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"285462"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/285462","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31761376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of copper and cholesterol association in the neurodegenerative process.","authors":"Nathalie Arnal,&nbsp;Gustavo R Morel,&nbsp;María J T de Alaniz,&nbsp;Omar Castillo,&nbsp;Carlos A Marra","doi":"10.1155/2013/414817","DOIUrl":"https://doi.org/10.1155/2013/414817","url":null,"abstract":"<p><p>Age is one of the main factors involved in the development of neurological illnesses, in particular, Alzheimer, and it is widely held that the rapid aging of the world population is accompanied by a rise in the prevalence and incidence of Alzheimer disease. However, evidence from recent decades indicates that Cu and Cho overload are emerging causative factors in neurodegeneration, a hypothesis that has been partially investigated in experimental models. The link between these two variables and the onset of Alzheimer disease has opened up interesting new possibilities requiring more in-depth analysis. The aim of the present study was therefore to investigate the effect of the association of Cu + Cho (CuCho) as a possible synergistic factor in the development of an Alzheimer-like pathology in Wistar rats. We measured total- and nonceruloplasmin-bound Cu and Cho (free and sterified) contents in plasma and brain zones (cortex and hippocampus), markers of oxidative stress damage, inflammation, and programmed cell death (caspase-3 and calpain isoforms). The ratio beta-amyloid (1-42)/(1-40) was determined in plasma and brain as neurodegenerative biomarker. An evaluation of visuospatial memory (Barnes maze test) was also performed. The results demonstrate the establishment of a prooxidative and proinflammatory environment after CuCho treatment, hallmarked by increased TBARS, protein carbonyls, and nitrite plus nitrate levels in plasma and brain zones (cortex and hippocampus) with a consequent increase in the activity of calpains and no significant changes in caspase-3. A simultaneous increase in the plasma A β 1-42/A β 1-40 ratio was found. Furthermore, a slight but noticeable change in visuospatial memory was observed in rats treated with CuCho. We conclude that our model could reflect an initial stage of neurodegeneration in which Cu and Cho interact with one another to exacerbate neurological damage. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"414817"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/414817","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31911744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetylcholinesterase inhibitors promote angiogenesis in chick chorioallantoic membrane and inhibit apoptosis of endothelial cells.","authors":"Seyed Mohsen Mortazavian, Heydar Parsaee, Seyed Hadi Mousavi, Zahra Tayarani-Najaran, Ahmad Ghorbani, Hamid Reza Sadeghnia","doi":"10.1155/2013/121068","DOIUrl":"10.1155/2013/121068","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is one of the most common causes of dementia in the elderly. Recently, a great attention has been paid to the possible role of vascular changes in the pathogenesis of AD. Reduced microvascular density and degeneration of the endothelium are of structural cerebrovascular changes in AD. Acetylcholinesterase (AChE) inhibitors are widely used for the improvement of AD symptoms. Until now, however, the effects of AChE inhibitors on vascular changes including angiogenesis and endothelial cell apoptosis are not fully understood. In the present work, the effects of three AChE inhibitors (donepezil, rivastigmine, and galantamine) were tested on H2O2-induced apoptosis in human umbilical vein endothelial cells (HUVECs) and on angiogenesis in chicken chorioallantoic membrane model. Incubation of HUVEC with H2O2 led to a significant decrease in cell viability and an increase in the percentage of apoptotic cells. The tested drugs, at concentrations of 1-100  μ M, significantly inhibited the H2O2-induced toxicity. Also, all donepezil, rivastigmine and galantamine significantly increased the number of vessels in the chorioallantoic membrane when injected into fertilized eggs. In conclusion, AChE inhibitors possess angiogenesis-accelerating properties and have antiapoptotic effects on endothelial cells. These effects of AChE inhibitors may be involved in their beneficial effects on AD. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":" ","pages":"121068"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40265989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical trial of a home safety toolkit for Alzheimer's disease.","authors":"Kathy J Horvath, Scott A Trudeau, James L Rudolph, Paulette A Trudeau, Mary E Duffy, Dan Berlowitz","doi":"10.1155/2013/913606","DOIUrl":"10.1155/2013/913606","url":null,"abstract":"<p><p>This randomized clinical trial tested a new self-directed educational intervention to improve caregiver competence to create a safer home environment for persons with dementia living in the community. The sample included 108 patient/caregiver dyads: the intervention group (n = 60) received the Home Safety Toolkit (HST), including a new booklet based on health literacy principles, and sample safety items to enhance self-efficacy to make home safety modifications. The control group (n = 48) received customary care. Participants completed measures at baseline and at twelve-week follow-up. Multivariate Analysis of Covariance (MANCOVA) was used to test for significant group differences. All caregiver outcome variables improved in the intervention group more than in the control. Home safety was significant at P ≤ 0.001, caregiver strain at P ≤ 0.001, and caregiver self-efficacy at P = 0.002. Similarly, the care receiver outcome of risky behaviors and accidents was lower in the intervention group (P ≤ 0.001). The self-directed use of this Home Safety Toolkit activated the primary family caregiver to make the home safer for the person with dementia of Alzheimer's type (DAT) or related disorder. Improving the competence of informal caregivers is especially important for patients with DAT in light of all stakeholders reliance on their unpaid care. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"913606"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31835869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"γ -Secretase Pharmacology: What Pharmacology Will Work for Alzheimer's Disease?","authors":"Jeremy H Toyn,&nbsp;Adele Rowley,&nbsp;Yasuji Matsuoka,&nbsp;Taisuke Tomita,&nbsp;Bruno P Imbimbo","doi":"10.1155/2013/849128","DOIUrl":"https://doi.org/10.1155/2013/849128","url":null,"abstract":"This special issue focuses on γ-secretase modulators (GSMs) and inhibitors (GSIs), two classes of small molecules with the potential to test the amyloid hypothesis of Alzheimer's disease. Recent clinical trials of GSI and GSM, including semagacestat, avagacestat, and R-flurbiprofen, have been discontinued for lack of efficacy and/or side effects, the mechanisms of which have not been elucidated. Detrimental effects of GSIs on cognition observed in AD patients may be linked to the accumulation of C-terminal fragment of APP (C99 or CTFβ). The stimulating effects of GSIs on skin cancer in AD patients have been linked to their inhibition of Notch processing. The lack of efficacy of the GSM R-flurbiprofen in AD patients has been explained with its low potency and poor ability to cross the blood-brain barrier. The two review articles and three research articles address key issues for GSI and GSM, namely, Notch-related side effects and drug-like properties, respectively. Although other amyloid-related approaches are continuing in clinical trials, including anti-Aβ antibodies and β-site amyloid precursor protein cleaving enzyme (BACE) inhibitors, it still remains to be seen whether or not they can decrease amyloid or Aβ for a sufficient period of time at tolerable doses in patients. Therefore, renewed efforts toward GSIs and GSMs appear justified.","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"849128"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/849128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31458641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}