Facilitating social coping-‘seeking emotional and practical support from others’-as a critical strategy in maintaining the family care of people with dementia

The aim of this study was to identify how the family care of people living with dementia could be supported to make reliance on family care sustainable in the long term despite the impact of stress. A Realist Evaluation (Pawson & Tilley, 1997) was conducted to investigate this aim. An initial review established ‘coping’ as a primary means of mediating stressors associated with caregiving. However, there was a need to specify which coping approaches/strategies are most effective. In-depth interviews were conducted with a purposive sample of family carers (n = 18) in a suburb in North East England from 2016 to 2017. Analysis of the data revealed ‘social coping’ (SC) that included an emotional support component as a critical mediator of family carer stress. Several key hindrances to the utilisation of SC, including underpinning causal factors, are explicated. Ways in which these hindrances might be overcome are discussed and guidelines introduced for how family carers, formal providers and practitioners can facilitate SC as a critical coping strategy in sustaining the family care of people with dementia over the long term

A mind-body approach to promote health and enhance healing

The purpose of this project was to create for the public a research-based user-friendly booklet that provides guidance with regard to psychological considerations that may be employed to enhance, or accelerate, the process of healing from illness

Chemical, molecular pharmacology and neuroprotective properties of the essential oil derived from Aloysia citrodora Palau

Essential oils derived from dried and fresh leaves of Aloysia citrodora were obtained by hydrodistillation, and were investigated for a range of pharmacological properties: receptor binding, in vitro acetylcholinesterase (AChE) inhibitory, antioxidant activities, and neuroprotection properties relevant to neurodegenerative diseases. Fresh leaf A. citrodora essential oil inhibited [3H] nicotine binding to well washed rat forebrain membranes, with mean apparent IC50 of 0.0018 mg/ml. No significant binding activity was observed for A. citrodora essential oil derived from fresh or dried leaves, for GABAAR and NMDARs. A. citrodora essential oil, both dried and fresh, exhibited radical scavenging activity (up to 100%, IC50 < 0.0001 mg/ml) and iron (II) chelating properties (approx. IC50 = 0.05 mg/ml), and showed neuroprotective characteristics against the toxic effects of H2O2 (100%, 0.001 mg/ml) and β-amyloid (approx. 50%, 0.01 mg/ml) in CAD neuronal cell culture. Both EOs from dried and fresh leaves also displayed effective AChE inhibitory activity, with the dried leaves oil displaying more clear AChE inhibitory activity than fresh oil, which could be related to the higher respective levels of caryophyllene oxide. Recombinant human anticholinesterase enzyme was used for structure based in silico screening of A. citrodora essential oil constituents for AChE Inhibitors, and the top scoring hits with highest pharmacophore fit values showed common interactions with residues at the active site of that of donepezil. The top seven hits in order of fit score, were β-curcumene, curcumene bisabolene, trans-calamenene, caryophyllene oxide, β-sesquiphellandrene and geranyl acetate. This indicates that plants may yield novel effective and safe AChE inhibitors, other than alkaloids. To begin to identify the chemicals underpinning the pharmacological properties of A. citrodora, GC/MS analysis of the chemical composition of the essential oil from leaves of A. citrodora identified eighty three major chemicals, including the presence of terpenoids, monoterpenes and sesquiterpenes, and 6-methyl-5-hepten-2-one, the main constituents being limonene, caryophyllene oxide, curcumene, spathulenol, 1,8-cineole constituting 47% of the total oil. Finally, a simple, inexpensive solid phase extraction method was developed for fractionation of essential oils. Collectively, this thesis provides a better understanding of the pharmacology of the Aloysia essential oil and its constituents relating to its potential use in the treatment neurodegenerative disease

Extracts of salvia species : relation to potential cognitive therapy

BACKGROUND: Dementia is a neurodegenerative disease of the brain associated with cognitive and memory impairments. Despite recognition of several types of dementia, the Alzheimer type is the most studied and understood. The cholinergic theory of Alzheimer's disease led to the development of licensed drugs based on the inhibition of the enzyme acetylcholinesterase. Extracts of Salvia (sage) species have been reported to have cholinergic activities relevant to the treatment of Alzheimer's disease. AIMS: Lack of information on a chemical fingerprint of the extracts responsible for inhibition of the enzymes butyrylcholinesterase and acetylcholinesterase prompted this in vitro investigation of sage species for anti-cholinesterase activity. Cholinergic receptor binding activity, inhibition of ß-secretase, and a pro-inflammatory cytokine suppressive activity of extracts of sage species were also studied as relevant treatment targets. METHODS: The extracts were obtained by methods of supercritical fluid extraction using 1,1,1,2-tetrafluoroethane (Phytosol A) and steam distillation. Dose-dependant inhibition of human cholinesterases by the extracts and constituents was determined using the method of Ellman, while inhibition of ß-secretase via a fluorometric method. The nicotinic acetylcholine receptors binding activity was measured as an amount of [3H]-nicotine displaced from human acetylcholine receptors, whereas the muscarinic activity was assessed using the displacement of [3H]-scopolamine. Determination of interleukin 8 inhibitory activity by the extracts was performed via a quantitative sandwich enzyme immunoassay using a commercially available kit. RESULTS: Inhibition of butyrylcholinesterase by the Phytosol extracts of S. apiana, S. fruticosa and S. officinalis var. purpurea was non-competitive. In contrast, inhibition of acetylcholinesterase by S. officinalis var. purpurea oil was competitive. S. corrugata extract was the most potent inhibitor of acetylcholinesterase with an IC50 value of 0.009±0.004 mg ml", while S. officinalis var. purpurea oil was the most active inhibitor of butyrylcholinesterase with an IC50 value of 0.015±0.004 mg ml''. Time dependent increase in inhibition of butyrylcholinesterase by steam distilled oils of S. fruticosa and S. officinalis var. "purpurea" was also evident. IC50 values decreased from 0.15±0.007 and 0.14±0.007 mg ml-1 with 5 minutes to 0.035±0.016 and 0.06±0.018 mg ml-1 with 90 minutes incubation time respectively. Phytosol A extracts were more potent than steam distilled oils with respect to anti-cholinesterase activity. Minor synergy in inhibition of bovine acetylcholinesterase was apparent in 1,8-cineole/a-pinene and 1,8- cineole/caryophyllene oxide combinations, whereas a combination of camphor and 1,8- cineole was antagonistic. Oil of S. apiana displaced [3H]-nicotine from human nicotinic acetylcholine receptors and [3H]-scopolamine from muscarinic acetylcholine receptors in a dose dependent manner with IC50 values of 0.02 mg ml" and IC50 0.1 mg ml" respectively. This oil also showed a modest suppression of interleukin 8 secretions from goblet cells. None of the tested oils and constituents had anti-ß secretase activity. CONCLUSION: These findings demonstrate that the cholinergic activity of the extracts results from a complex interaction between their constituents. Thus, inhibition of acetylcholinesterase is mainly due to the activity of the main constituents with some degree of synergy, whereas anti-butyrylcholinesterase activity is down to major synergistic interactions and identification of a chemical fingerprint responsible for the overall activity is therefore challenging. A synergistic combination of extracts or their standardised fractions with multiple activities is may be a candidate for clinical trials in Alzheimer's disease.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

NUTRITION CARE FOR LONG-TERM CARE RESIDENTS WITH DEMENTIA IN URBAN AND RURAL CONTEXTS: AN EVIDENCE BASED PRACTICE EXAMINATION OF THE ROLE OF CARE AIDES AND REGISTERED DIETITIANS

This doctoral dissertation contributes to the body of knowledge pertaining to nutrition care for persons with dementia. The aging population adds to the increased risk for and prevalence of dementia globally. Alongside this is a recognition of the need for care strategies for persons with dementia, and preventive strategies to delay onset of dementia or to delay secondary or tertiary comorbidity associated with dementia. Of strong interest is the field of nutrition, in terms of dietary strategies for primary prevention of dementia, for secondary and tertiary prevention of comorbidities, and for medical nutrition therapies to treat those with dementia, across the spectrum of dementing illnesses and degree of severity. Over the course of three related studies, nutrition care for long-term care (LTC residents was addressed using an evidence-based practice lens. Study 1 investigated care aides’ perception of nutrition care for urban and rural LTC residents with dementia. Key findings included the complexity of operationalizing person centered care into nutrition care activities, the mechanistic focus on feeding, and many organizational factors that direct nutrition care for care aides and residents with dementia. Study 2 examined the role of registered dietitians (RDs) in providing nutrition care for residents with dementia in urban and rural LTC. The key finding in this study was the downstream role of RDs in dementia care. As opposed to a more upstream preventive model of care, RDs were consulted or involved only at late stages or when comorbid decline had occurred, limiting their abilities to use their specialized nutrition knowledge and skills effectively. The 3rd study was an umbrella review of the peer-reviewed body of systematic reviews on nutrition care for residents with dementia in LTC. The major findings of this study include the lack of consistency in terms of nutritional outcomes considered and intervention tested, as well as a considerable gap in the published literature regarding both care aides and RDs. Taken together, these studies make a valuable contribution to the growing body of research on nutrition care and dementia. There is a need to continue to work with RDs and care aides in developing and testing interventions that can enhance both the physical health and quality of life for LTC residents with dementia

New [18F]Tracers for Alzheimer's Disease Imaging. Labeling Synthesis And Biological Testing

Alzheimer’s disease (AD) is the most common form of dementia. Characteristic changes in an AD brain are the formation of β-amyloid protein (Aβ) plaques and neurofibrillary tangles, though other alterations in the brain have also been connected to AD. No cure is available for AD and it is one of the leading causes of death among the elderly in developed countries. Liposomes are biocompatible and biodegradable spherical phospholipid bilayer vesicles that can enclose various compounds. Several functional groups can be attached on the surface of liposomes in order to achieve long-circulating target-specific liposomes. Liposomes can be utilized as drug carriers and vehicles for imaging agents. Positron emission tomography (PET) is a non-invasive imaging method to study biological processes in living organisms. In this study using nucleophilic 18F-labeling synthesis, various synthesis approaches and leaving groups for novel PET imaging tracers have been developed to target AD pathology in the brain. The tracers were the thioflavin derivative [18F]flutemetamol, curcumin derivative [18F]treg-curcumin, and functionalized [18F]nanoliposomes, which all target Aβ in the AD brain. These tracers were evaluated using transgenic AD mouse models. In addition, 18F-labeling synthesis was developed for a tracer targeting the S1P3 receptor. The chosen 18F-fluorination strategy had an effect on the radiochemical yield and specific activity of the tracers. [18F]Treg-curcumin and functionalized [18F]nanoliposomes had low uptake in AD mouse brain, whereas [18F]flutemetamol exhibited the appropriate properties for preclinical Aβ-imaging. All of these tracers can be utilized in studies of the pathology and treatment of AD and related diseases.Alzheimerin tauti on yleisin dementiasairaus. Tyypillisimmät Alzheimerin taudin aiheuttamat muutokset ovat β-amyloidi(Aβ)proteiinista koostuvien plakkien sekä hermosäievyyhteiden muodostuminen aivoihin. Alzheimerin tautiin on liitetty myös muita aivomuutoksia. Tällä hetkellä Alzheimerin tautiin ei ole parantavaa hoitoa. Ikääntyneiden keskuudessa Alzheimerin tauti on yksi tavallisimmista kuolemaan johtavista syistä. Liposomit ovat biologisesti yhteensopivia, luontaisesti hajoavia, pallomaisia kaksoisfosfolipidikerroksellisia vesikkeleitä, jotka voivat sulkea sisälleen erilaisia yhdisteitä. Liposomin pintaan voidaan liittää useita erilaisia funktionaalisia ryhmiä, jotta saadaan elimistössä pitkään kiertäviä, tarkoin kohdennettuja liposomeja. Liposomeja voidaan käyttää lääkeaineiden ja kuvantamisaineiden kuljettimina. Positroniemissiotomografia (PET) on kuvantamismenetelmä, jonka avulla voidaan tutkia biologisia prosesseja elävässä eliössä. Tässä tutkimuksessa nukleofiiliseen 18F-fluorileimaukseen perustuvien synteesireittien avulla kehitettiin uusia merkkiaineita Alzheimerin taudin aivomuutosten tutkimiseen. Kehitetyt merkkiaineet olivat tioflaviinijohdos [18F]flutemetamoli, kurkumiinijohdos [18F]treg-kurkumiini sekä funktionalisoituja [18F]nanoliposomeja. Kaikki nämä yhdisteet kohdistuivat Alzheimerin taudin Aβ plakkeihin. Merkkiaineet evaluoitiin käyttäen Alzheimerin tautia mallintavia siirtogeenihiiriä. Lisäksi kehitettiin S1P3-reseptoriin kohdentuvan merkkiaineen 18F-leimaussynteesi. Valitulla 18F-leimaussynteesistrategialla on vaikutusta merkkiaineen radiokemialliseen saantoon ja ominaisaktiivisuuteen. [18F]Treg-kurkumiini sekä funktionaaliset [18F]nanoliposomit kertyivät vain vähän koe-eläimen aivoihin, kun taas [18F]flutemetamoli osoittautui sopivan käyttökelpoiseksi prekliiniseen kuvantamiseen. Kaikkia tässä työssä kehitettyjä merkkiaineita voidaan käyttää tutkittaessa Alzheimerin taudin ja samanlaisten sairauksien patologiaa ja hoitoa.Siirretty Doriast

Potential role of herbal plants and beta sitosterol as a bioactive constituent in circumventing Alzheimer’s Disease

Alzheimer's Disease (AD), a neurological ailment, mostly affects the older population all around the world. The rational therapies show limited efficacy, adverse effects, and poor patient compliance; therefore, herbal drugs are considered a suitable supplement to the drug therapy for the treatment of AD. According to research, herbal drugs reduce symptoms of AD and also improve brain functioning through the inhibition of beta amyloid, gamma-secretase, and acetylcholine, along with the regulation of antioxidants and the activation of alpha-secretase. Various herbal plants like Salvia officinalis L., Bertholletia excelsa L., Withania somnifera L., and Urtica dioica L. help slow down the progression of AD by scavenging free radicals, inhibiting lipid peroxidation, beta amyloid and tau phosphorylation. Beta sitosterol, a phytosterol found abundantly in plants, has the ability to cross the Blood Brain Barrier and thus acts as a bioactive constituent in circumventing various neurological disorders. Numerous in vitro and in vivo investigations indicate that beta sitosterol shows immunomodulatory, lipid-lowering, as well as antioxidant properties. The plant sterol, beta sitosterol, has the capacity to decrease beta-amyloid platelet synthesis, indicating that it might be helpful in the treatment and prevention of AD. Treatment with beta-sitosterol can lessen plaque burden and also enhance spatial learning and recognition abilities in patients suffering from AD

Deep Interpretability Methods for Neuroimaging

Brain dynamics are highly complex and yet hold the key to understanding brain function and dysfunction. The dynamics captured by resting-state functional magnetic resonance imaging data are noisy, high-dimensional, and not readily interpretable. The typical approach of reducing this data to low-dimensional features and focusing on the most predictive features comes with strong assumptions and can miss essential aspects of the underlying dynamics. In contrast, introspection of discriminatively trained deep learning models may uncover disorder-relevant elements of the signal at the level of individual time points and spatial locations. Nevertheless, the difficulty of reliable training on high-dimensional but small-sample datasets and the unclear relevance of the resulting predictive markers prevent the widespread use of deep learning in functional neuroimaging. In this dissertation, we address these challenges by proposing a deep learning framework to learn from high-dimensional dynamical data while maintaining stable, ecologically valid interpretations. The developed model is pre-trainable and alleviates the need to collect an enormous amount of neuroimaging samples to achieve optimal training. We also provide a quantitative validation module, Retain and Retrain (RAR), that can objectively verify the higher predictability of the dynamics learned by the model. Results successfully demonstrate that the proposed framework enables learning the fMRI dynamics directly from small data and capturing compact, stable interpretations of features predictive of function and dysfunction. We also comprehensively reviewed deep interpretability literature in the neuroimaging domain. Our analysis reveals the ongoing trend of interpretability practices in neuroimaging studies and identifies the gaps that should be addressed for effective human-machine collaboration in this domain. This dissertation also proposed a post hoc interpretability method, Geometrically Guided Integrated Gradients (GGIG), that leverages geometric properties of the functional space as learned by a deep learning model. With extensive experiments and quantitative validation on MNIST and ImageNet datasets, we demonstrate that GGIG outperforms integrated gradients (IG), which is considered to be a popular interpretability method in the literature. As GGIG is able to identify the contours of the discriminative regions in the input space, GGIG may be useful in various medical imaging tasks where fine-grained localization as an explanation is beneficial

Inhibición de la actividad de acetilcolinesterasa por el extracto hidroalcohólico y sus fracciones de Bouvardia ternifolia (Cav.) Shcltdl (Rubiaceae)

El extracto hidroalcohólico (BtHA) y fracciones provenientes de Bouvardia ternifolia fueron evaluadas como inhibidores de la enzima acetilcolinesterasa  utilizando el método enzimático propuesto por Ellman. BtHA  inhibe a la enzima de manera competitiva (IC50 = 0.6 g/ml); la fracción de acetato de etilo  (BtF-AcOEt) provoca una inhibición mixta (IC50 = 0.96 g/ml). La fracción insoluble en metanol (Bt-Faq-1) mostró una inhibición tipo mixta (CI50 = 0.96  g/ml). Finalmente la fracción soluble en metanol, Bt-Faq-2, inhibe a la enzima presentando una inhibición mixta que corresponde a un sistema C5 (  = 0.740  and  = 0.842). Mediante HPLC se detectó rutina, quercetina, canferol y ácido ursólico la concentración de estos compuestos fue diferente en cada fracción