The spatial patterns of β-amyloid (Aβ) deposits and neurofibrillary tangles (NFT) in late-onset sporadic Alzheimer's disease

The spatial patterns of β-amyloid (Aβ) deposits and neurofibrillary tangles (NFT) were studied in areas of the cerebral cortex in 16 patients with the late-onset, sporadic form of Alzheimer's disease (AD). Diffuse, primitive, and classic Aβ deposits and NFT were aggregated into clusters; the clusters being regularly distributed parallel to the pia mater in many areas. In a significant proportion of regions, the sizes of the regularly distributed clusters approximated to those of the cells of origin of the cortico-cortical projections. The diffuse and primitive Aβ deposits exhibited a similar range of spatial patterns but the classic Aβ deposits occurred less frequently in large clusters >6400m. In addition, the NFT often occurred in larger regularly distributed clusters than the Aβ deposits. The location, size, and distribution of the clusters of Aβ deposits and NFT supports the hypothesis that AD is a 'disconnection syndrome' in which degeneration of specific cortico-cortical and cortico-hippocampal pathways results in synaptic disconnection and the formation of clusters of NFT and Aβ deposits. © 2011 Nova Science Publishers, Inc.

Kereslet-előrejelzés sporadikus keresletű termékekre: Egy gyógyszer-nagykereskedelmi vállalat esettanulmánya (Forecasting of Sporadic Products - A Case Study of a Pharmaceutical Wholesaler Company)

A vállalatok jelentős része szembesül azzal, hogy termékei jelentős része iránt viszonylag kevés alkalommal jelentkezik kereslet. Ebből következik, hogy az ilyen termékekre a klasszikus előrejelzési módszerek, mint pl. a mozgó átlag számítása, vagy az exponenciális simítás nem alkalmazható. Azon termékeket, amelyek iránt viszonylag ritkán jelenik meg kereslet, sporadikus keresletű termékeknek nevezzük. A megkülönböztetés a sporadikus és nem sporadikus termékek között sokszor csak hüvelykujj szabály alapján állapítható meg, de erre vonatkozóan a szakirodalomban találunk iránymutatást. A nemzetközi szakirodalomban már megjelentek olyan új kereslet-előrejelzési módszerek, melyeket kimondottan az ilyen, sporadikus kereslettel rendelkező termékek estében javasoltak. Cikkünk célja, hogy ezeket a szakirodalmi ajánlásokat egy konkrét hazai vállalat valós adatain esettanulmány jelleggel tesztelje. A nemzetközi szakirodalomban is ritkán publikálnak tudományos dolgozatokat, amelyek ezt a témakört valós alkalmazási környezetben tárgyalják; ismereteink szerint magyar nyelven erről tudományos dolgozat pedig még nem született. Elméleti bevezetőnk után egy gyógyszer-nagykereskedelmi vállalatnál valós adatait használva vizsgáljuk a kérdéskört. Sor kerül a vállalat termékportfóliójának a kereslet-előrejelzés szempontjából történő tipizálására, majd sporadikus keresletű termékek keresletének előrejelzésére és ennek során a szakirodalomban az alkalmazandó módszerekre vonatkozó ajánlások vizsgálatára. _____ Significant numbers of companies have the problem that demand for their products are sporadic in nature. Demand of such products is not continual in time; its demand is diffused, is random with large proportion of zero values in the analyzed time series. The sporadic character of a demand pattern actually means that available information on the demand of previous selling periods is leaky resulting in lower quality of data available. In these cases traditional forecasting techniques do not result in reliable forecast. Special forecasting algorithms have been developed during the last decade dealing with this problem. The paper introduces these techniques and offers suggestions for application. It also presents the case study of a Hungarian pharmaceutical wholesaler company. Based on real data we develop a topology of the company's product portfolio, carry out forecasts using different techniques including those developed for products with sporadic demand and also analyze the quality of these forecasts.

The relationship between coping strategies and level of depression among spousal caregivers of elders with dementia

Caregivers are often under a great deal of stress while caring for their spouses with dementia. It is when the stress builds up and becomes overwhelming that the caregiver is at risk for developing depression. The primary objective of this study was to determine which cognitive and behavioral coping strategies are associated with lower levels of depression; once these strategies are identified, interventions can be established to educate these caregivers. Thirty-two spousal caregivers participated in this study. They each filled out a questionnaire, which contained three sections. The first section asked them for demographic information about themselves and their spouses; the second section consisted of a coping strategies scale; and, the third section contained a depression scale. Results of this study indicate that problem-focused coping strategies were associated with a lesser degree of depressive symptomatology, whereas most of the emotion-focused strategies were associated with a greater degree of depressive symptomatology among the present sample of spousal caregivers. In addition, no relationship was found between the length of time providing care to their spouses and their level of depression.

Longitudinal diffusion tensor imaging in dementia with Lewy bodies and Alzheimer's disease

Copyright © 2016 Elsevier Ltd. All rights reserved. Acknowledgements The study was supported by the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. Elijah Mak was in receipt of a Gates Cambridge PhD studentship.

Mutant tau knock-in mice display frontotemporal dementia relevant behaviour and histopathology

Peer reviewed

Whole-brain patterns of 1H-magnetic resonance spectroscopy imaging in Alzheimer's disease and dementia with Lewy bodies

Acknowledgments We thank Craig Lambert for his help in processing the MRS data. The study was funded by the Sir Jules Thorn Charitable Trust (grant ref: 05/JTA) and was supported by the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre and the Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne Hospitals National Health Service (NHS) Foundation Trust and Newcastle University and the NIHR Biomedical Research Centre and Biomedical Research Unit in Dementia based at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

The effects of centrally acting ACE inhibitors on the rate of cognitive and functional decline in dementia: a KDD approach

Alzheimer’s Disease and other dementias are one of the most challenging illnesses confronting countries with ageing populations. Treatment options for dementia are limited, and the costs are significant. There is a growing need to develop new treatments for dementia, especially for the elderly. There is also growing evidence that centrally acting angiotensin converting enzyme (ACE) inhibitors, which cross the blood-brain barrier, are associated with a reduced rate of cognitive and functional decline in dementia, especially in Alzheimer’s disease (AD). The aim of this research is to investigate the effects of centrally acting ACE inhibitors (CACE-Is) on the rate of cognitive and functional decline in dementia, using a three phased KDD process. KDD, as a scientific way to process and analysis clinical data, is used to find useful insights from a variety of clinical databases. The data used are from three clinic databases: Geriatric Assessment Tool (GAT), the Doxycycline and Rifampin for Alzheimer’s Disease (DARAD), and the Qmci validation databases, which were derived from several different geriatric clinics in Canada. This research involves patients diagnosed with AD, vascular or mixed dementia only. Patients were included if baseline and end-point (at least six months apart) Standardised Mini-Mental State Examination (SMMSE), Quick Mild Cognitive Impairment (Qmci) or Activities Daily Living (ADL) scores were available. Basically, the rates of change are compared between patients taking CACE-Is, and those not currently treated with CACE-Is. The results suggest that there is a statistically significant difference in the rate of decline in cognitive and functional scores between CACE-I and NoCACE-I patients. This research also validates that the Qmci, a new short assessment test, has potential to replace the current popular screening tests for cognition in the clinic and clinical trials.

Nurses’ perceptions of nursing presence and the relationship between nursing presence and moral sensitivity in nurses working with people with dementia in residential care

Aim: The aim of this study was to measure nursing presence among nurses caring for people with dementia in residential care settings, and to investigate the relationship between nursing presence and moral sensitivity. Background: Nursing presence is a core relational skill in nursing and holds many benefits for nurses and their patients. Moral sensitivity is defined as how one recognises the moral elements of a situation, and how one’s moral or ethical decision making may impact on an individual. Methods: A descriptive, cross sectional quantitative methodology was used with a sample of 150 registered nurses. The Presence of Nursing Scale for Registered Nurses was used to investigate nursing presence, and the Moral Sensitivity Questionnaire for moral sensitivity. Results: Findings from the study demonstrated that participants agreed with the majority of elements of nursing presence, (mean 76.97, SD= 7.51). A mean score of 36.22 was evidence of a well developed level of moral sensitivity in participants. Nurses who perceived themselves to be highly present to their patients also scored highest on certain elements of moral sensitivity such as moral strength. Nursing presence was also found to be more developed in those participants that rated themselves as having higher levels of expertise based on Benner’s (1984) definitions. Older nurses also scored higher on nursing presence. There was a high level of agreement that factors such as lack of time (n=133), and heavy workload influenced nursing presence. Nurses, who were older and had longer clinical experience, were shown to have greater moral strength. There were differences in elements of moral sensitivity between groups of nurses who ranked themselves according to Benner’s (1984) competence framework with higher scores evident in the more expert groups. Conclusion: Overall, this study showed that participants had a well developed level of nursing presence, and certain elements of moral sensitivity are positively related to nursing presence. Nursing presence appears to be linked to the level of expertise of the nurse but factors such as time and workload do influence nursing presence.

Nurses' experiences of pain management for people with advanced dementia approaching the end of life: a qualitative study

AIMS AND OBJECTIVES: To explore hospice, acute care and nursing home nurses' experiences of pain management for people with advanced dementia in the final month of life. To identify the challenges, facilitators and practice areas requiring further support.

BACKGROUND: Pain management in end-stage dementia is a fundamental aspect of end of life care; however, it is unclear what challenges and facilitators nurses experience in practice, whether these differ across care settings, and whether training needs to be tailored to the context of care.

DESIGN: A qualitative study using semi-structured interviews and thematic analysis to examine data.

METHODS: 24 registered nurses caring for people dying with advanced dementia were recruited from ten nursing homes, three hospices, and two acute hospitals across a region of the United Kingdom. Interviews were conducted between June 2014 and September 2015.

RESULTS: Three core themes were identified: challenges administering analgesia, the nurse-physician relationship, and interactive learning and practice development. Patient-related challenges to pain management were universal across care settings; nurse- and organisation-related barriers differed between settings. A need for interactive learning and practice development, particularly in pharmacology, was identified.

CONCLUSIONS: Achieving pain management in practice was highly challenging. A number of barriers were identified; however, the manner and extent to which these impacted on nurses differed across hospice, nursing home and acute care settings. Needs-based training to support and promote practice development in pain management in end-stage dementia is required.

RELEVANCE TO CLINICAL PRACTICE: Nurses considered pain management fundamental to end of life care provision; however, nurses working in acute care and nursing home settings may be under-supported and under-resourced to adequately manage pain in people dying with advanced dementia. Nurse-to-nurse mentoring and ongoing needs-assessed interactive case-based learning could help promote practice development in this area. Nurses require continuing professional development in pharmacology. This article is protected by copyright. All rights reserved.

A Validation Study of Vascular Cognitive Impairment Genetics Meta-Analysis Findings in an Independent Collaborative Cohort

Vascular cognitive impairment (VCI), including its severe form, vascular dementia (VaD), is the second most common form of dementia. The genetic etiology of sporadic VCI remains largely unknown. We previously conducted a systematic review and meta-analysis of all published genetic association studies of sporadic VCI prior to 6 July 2012, which demonstrated that APOE (ɛ4, ɛ2) and MTHFR (rs1801133) variants were associated with susceptibility for VCI. De novo genotyping was conducted in a new independent relatively large collaborative European cohort of VaD (nmax = 549) and elderly non-demented samples (nmax = 552). Where available, genotype data derived from Illumina's 610-quad array for 1210 GERAD1 control samples were also included in analyses of genes examined. Associations were tested using the Cochran-Armitage trend test: MTHFR rs1801133 (OR = 1.36, 95% CI 1.16-1.58, p = <0.0001), APOE rs7412 (OR = 0.62, 95% CI 0.42-0.90, p = 0.01), and APOE rs429358 (OR = 1.59, 95% CI 1.17-2.16, p = 0.003). Association was also observed with APOE epsilon alleles; ɛ4 (OR = 1.85, 95% CI 1.35-2.52, p = <0.0001) and ɛ2 (OR = 0.67, 95% CI 0.46-0.98, p = 0.03). Logistic Regression and Bonferroni correction in a subgroup of the cohort adjusted for gender, age, and population maintained the association of APOE rs429358 and ɛ4 allele.