Staff experiences of a reablement approach to care for older people in a regional Australian community : a qualitative study

Reablement is described as a person-centred, goal-directed intervention with a view to regain, maintain or improve the independence of older clients. Although evidence to support the use of reablement as a multidisciplinary, home-based intervention for community-dwelling older adults is increasing, there is limited knowledge about what it means for care staff who provide client-based services. This study, which was nested in a larger program evaluation, used a descriptive qualitative approach to explore direct care staff and care coordinator experiences of translating a reablement training program into practice for older people in a regional Australian community. Two months after the training program four focus groups were conducted with 13 care coordinators to assimilate staff experiences with development of care plans, systems, processes and practices of reablement. In addition, four direct care staff took part in individual interviews, which centred on eliciting their experience using the reablement approach with clients. Results from the care coordinator focus groups and the direct care staff interviews highlight the importance of reablement staff training and the involvement of staff in the development and delivery of a reablement approach to client-centred care. A number of organisational and client-centred challenges such as communication, functional partnerships, staff education and resourcing are also uncovered in this research into the development of a reablement-focused care service in a regional setting. Overall there is support for the dominating discourse around healthy ageing and the policy approach of ageing in place to support wellness

A Novel Neurotrophic Drug for Cognitive Enhancement and Alzheimer's Disease

Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimer's disease (AD), the focus is the amyloid beta peptide (Aß) that mediates familial Alzheimer's disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model

The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer's disease mice

Abstract Introduction Despite years of research, there are no disease-modifying drugs for Alzheimer's disease (AD), a fatal, age-related neurodegenerative disorder. Screening for potential therapeutics in rodent models of AD has generally relied on testing compounds before pathology is present, thereby modeling disease prevention rather than disease modification. Furthermore, this approach to screening does not reflect the clinical presentation of AD patients which could explain the failure to translate compounds identified as beneficial in animal models to disease modifying compounds in clinical trials. Clearly a better approach to pre-clinical drug screening for AD is required. Methods To more accurately reflect the clinical setting, we used an alternative screening strategy involving the treatment of AD mice at a stage in the disease when pathology is already advanced. Aged (20-month-old) transgenic AD mice (APP/swePS1ΔE9) were fed an exceptionally potent, orally active, memory enhancing and neurotrophic molecule called J147. Cognitive behavioral assays, histology, ELISA and Western blotting were used to assay the effect of J147 on memory, amyloid metabolism and neuroprotective pathways. J147 was also investigated in a scopolamine-induced model of memory impairment in C57Bl/6J mice and compared to donepezil. Details on the pharmacology and safety of J147 are also included. Results Data presented here demonstrate that J147 has the ability to rescue cognitive deficits when administered at a late stage in the disease. The ability of J147 to improve memory in aged AD mice is correlated with its induction of the neurotrophic factors NGF (nerve growth factor) and BDNF (brain derived neurotrophic factor) as well as several BDNF-responsive proteins which are important for learning and memory. The comparison between J147 and donepezil in the scopolamine model showed that while both compounds were comparable at rescuing short term memory, J147 was superior at rescuing spatial memory and a combination of the two worked best for contextual and cued memory. Conclusion J147 is an exciting new compound that is extremely potent, safe in animal studies and orally active. J147 is a potential AD therapeutic due to its ability to provide immediate cognition benefits, and it also has the potential to halt and perhaps reverse disease progression in symptomatic animals as demonstrated in these studies

Cyclodextrins Inhibit Replication of Scrapie Prion Protein in Cell Culture▿

Prion diseases are fatal neurodegenerative disorders that are caused by the conversion of a normal host-encoded protein, PrPC, to an abnormal, disease-causing form, PrPSc. This paper reports that cyclodextrins have the ability to reduce the pathogenic isoform of the prion protein PrPSc to undetectable levels in scrapie-infected neuroblastoma cells. Beta-cyclodextrin removed PrPSc from the cells at a concentration of 500 μM following 2 weeks of treatment. Structure activity studies revealed that antiprion activity was dependent on the size of the cyclodextrin. The half-maximal inhibitory concentration (IC50) for beta-cyclodextrin was 75 μM, whereas α-cyclodextrin, which possessed less antiprion activity, had an IC50 of 750 μM. This report presents cyclodextrins as a new class of antiprion compound. For decades, the pharmaceutical industry has successfully used cyclodextrins for their complex-forming ability; this ability is due to the structural orientation of the glucopyranose units, which generate a hydrophobic cavity that can facilitate the encapsulation of hydrophobic moieties. Consequently, cyclodextrins could be ideal candidates for the treatment of prion diseases

Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer's disease transgenic mice.

Alzheimer's disease (AD) is the most common type of dementia. It is the only one of the top ten causes of death in the USA for which prevention strategies have not been developed. Although AD has traditionally been associated with the deposition of amyloid β plaques and tau tangles, it is becoming increasingly clear that it involves disruptions in multiple cellular systems. Therefore, it is unlikely that hitting a single target will result in significant benefits to patients with AD. An alternative approach is to identify molecules that have multiple biological activities that are relevant to the disease. Fisetin is a small, orally active molecule which can act on many of the target pathways implicated in AD. We show here that oral administration of fisetin to APPswe/PS1dE9 double transgenic AD mice from 3 to 12 months of age prevents the development of learning and memory deficits. This correlates with an increase in ERK phosphorylation along with a decrease in protein carbonylation, a marker of oxidative stress. Importantly, fisetin also reduces the levels of the cyclin-dependent kinase 5 (Cdk5) activator p35 cleavage product, p25, in both control and AD brains. Elevated levels of p25 relative to p35 cause dysregulation of Cdk5 activity leading to neuroinflammation and neurodegeneration. These fisetin-dependent changes correlate with additional anti-inflammatory effects, including alterations in global eicosanoid synthesis, and the maintenance of markers of synaptic function in the AD mice. Together, these results suggest that fisetin may provide a new approach to the treatment of AD

Determining readiness for a reablement approach to care in Australia : development of a pre-employment questionnaire

Reablement is described as a goal directed intervention with a view to maintain or improve the independence of clients through “doing with, rather than doing for”. As a relatively new concept in care, lack of specific skills in reablement is not uncommon, however, intrinsic values aligned with reablement are beneficial to organisations providing care and support to clients. The aim of this study is to develop a pre-employment questionnaire to assess readiness for a reablement approach to care as a step towards developing a reablement culture across organisations. A questionnaire based on activities of daily living (ADL), developed by the research team in consultation with a local community-based care organisation, was completed by 166 staff members at a community-based care organisation in Tasmania across several timepoints during and following reablement education sessions in 2018. The scores from these questionnaires were utilised to develop a questionnaire appropriate for determining readiness for reablement prior to employment within the organisation. Over a period of twelve months, a total of 407 Reablement Readiness Questionnaires were submitted by staff, indicating high levels of willingness to engage in reablement prior to and following the education sessions. Exploratory factor analyses were performed, and the construct validity and internal consistency of the emerging factors were assessed. An exploratory factor analysis indicated that ADL, in relation to reablement, consist of three dimensions—Lifestyle, My body and Connecting. The corresponding questions were subsequently built into an online questionnaire for pre-employment use. This questionnaire also has potential benefit in recruitment of staff to other community service organisations, to ascertain their readiness for reablement prior to beginning a variety of different roles within client care and support

A comprehensive multiomics approach toward understanding the relationship between aging and dementia.

Because age is the greatest risk factor for sporadic Alzheimer's disease (AD), phenotypic screens based upon old age-associated brain toxicities were used to develop the potent neurotrophic drug J147. Since certain aspects of aging may be primary cause of AD, we hypothesized that J147 would be effective against AD-associated pathology in rapidly aging SAMP8 mice and could be used to identify some of the molecular contributions of aging to AD. An inclusive and integrative multiomics approach was used to investigate protein and gene expression, metabolite levels, and cognition in old and young SAMP8 mice. J147 reduced cognitive deficits in old SAMP8 mice, while restoring multiple molecular markers associated with human AD, vascular pathology, impaired synaptic function, and inflammation to those approaching the young phenotype. The extensive assays used in this study identified a subset of molecular changes associated with aging that may be necessary for the development of AD

Structure activity relationship of a few CNB-001 derivatives.

<p>The structure of CNB-001 is shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0027865#pone-0027865-g001" target="_blank">Figure 1A</a>. A series of CNB-001 derivatives were synthesized with the goal of removing the hydroxyl group and maintaining and/or improving biological activity in the glutamate based oxytosis assay and extracellular amyloid toxicity. Et (ethyl), Me (Methyl).</p

Preparation of J147.

<p>J147 was prepared as described in the chemistry section of the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0027865#s4" target="_blank">materials and methods</a>. The reagents and conditions for each step are as follows: (a) EtOH, rt, 1 h, 90%; (b) (CF₃CO)₂O, Et₃N, 30 min, 10°C, 77%.</p