Cholinesterase inhibitors (ChEIs) are the first line pharmacotherapy for the symptoms of Alzheimer’s disease (AD). Though ChEIs offer modest cognitive benefits in early AD, literature addressing their continued use in severe AD is scarce. This study assessed the safety of discontinuing ChEIs in institutionalized moderate-severe AD patients. Twenty-six patients were randomized, double-blind to ChEI continuation or placebo for 8-weeks. Vitals, weight (kg) and adverse events (AEs) were monitored biweekly. Chi-square test revealed no significant association between semi-blinded treatment allocation and AE occurrence (χ²=(1,26)=0.99, p=0.32). Groups showed no differences on clinically significant weight loss (χ²=(1,26) =1.9, p=0.17), mean weight loss (F=.531, p= .473), pulse rate (F=.624, p=.437), or side effects (F=.224, p=.640). Preliminary results suggest that either ChEIs are well tolerated or that these drugs are no longer providing therapeutic benefit. Study completion (recruitment of 60 patients and unblinding) will generate more comprehensive data for determination of safe ChEI discontinuation guidelines.

The effects of exogenous estrogen administration on aspects of memory and cognition in women were examined in two studies. In Study 1, women receiving estrogen replacement therapy were compared to untreated women on four measures of verbal memory. Those receiving estrogen had significantly better scores on a measure of delayed memory for propositional material. In Study 2, women in the early stages of Alzheimer's Disease (AD) were administered either estrogen or placebo on a double-blind basis for six months. Women given estrogen showed improvement on a measure of verbal memory and spatial attention compared to the placebo controls. The combined results of these studies provide evidence that estrogen enhances aspects of verbal memory in both healthy postmenopausal women and in postmenopausal women in the early stages of AD as measured by neuropsychological tests. These effects might be mediated by actions of estrogen on neuronal morphology and physiology in brain areas important for memory and cognition.

Cholinesterase inhibitors (ChEIs) are the first line pharmacotherapy for the symptoms of Alzheimer’s disease (AD). Though ChEIs offer modest cognitive benefits in early AD, literature addressing their continued use in severe AD is scarce. This study assessed the safety of discontinuing ChEIs in institutionalized moderate-severe AD patients. Twenty-six patients were randomized, double-blind to ChEI continuation or placebo for 8-weeks. Vitals, weight (kg) and adverse events (AEs) were monitored biweekly. Chi-square test revealed no significant association between semi-blinded treatment allocation and AE occurrence (χ²=(1,26)=0.99, p=0.32). Groups showed no differences on clinically significant weight loss (χ²=(1,26) =1.9, p=0.17), mean weight loss (F=.531, p= .473), pulse rate (F=.624, p=.437), or side effects (F=.224, p=.640). Preliminary results suggest that either ChEIs are well tolerated or that these drugs are no longer providing therapeutic benefit. Study completion (recruitment of 60 patients and unblinding) will generate more comprehensive data for determination of safe ChEI discontinuation guidelines.

Purpose: The purpose of this project was to look at the costs of individuals with Alzheimer’s disease and related dementias (ADRD), ALS, and MS in long stay home care in Ontario, Canada. The specific goals were to produce estimates of costs for these individuals, as well as identify clinical and personal characteristics associated with these costs. This project also tested the effectiveness of the Resource Utilization Group for home care case-mix system for use in these special populations. Methods: This project was conducted using a secondary analysis of assessment data from the Canadian Staff Time Resource Intensity Verification Project, a 13-week study of home care costs (N=435 141). The project was guided by the Andersen and Newman (1973) framework for healthcare resource utilization. Descriptive characteristics and mean costs were produced using bivariate frequency and means procedures for each of three conditions. Predictors of costs were identified for each of the three neurological conditions through multivariate regression analysis conducted separately for each condition. In total 41 independent variables were included into the bivariate and multivariate analyses. The dependent variable was the total weekly formal and informal home care costs across all multivariate analyses. Results: In total, ADRD, ALS, or MS diagnoses were present in 16% of the assessments. The mean costs for the three conditions combined were $594.81. The mean costs for ADRD, ALS, and MS were $593.32, $898.41, and $574.92, respectively. Characteristics that were predictive of cost across all conditions included the Resource Utilization Group for home care case-mix system, ADL functionality, IADL functionality, cognitive performance, unsteady gait, stair use, difficulty swallowing, respiratory challenges, and bowel incontinence. The Resource Utilization Group for home care case-mix system had the highest level of explained variance of any single item tested in this project across all conditions. However, other clinical characteristics also contributed substantial levels of explained variance to the models for each of the three conditions. Conclusions: The findings from this project suggest that although diagnosis of ADRD, ALS, and/or MS can describe cost, clinical characteristics are the most important predictors of costs for individuals with these conditions. In addition, the Resource Utilization Group for home care case-mix system can adequately predict costs of individuals with these conditions. The addition of some clinical characteristics would likely improve the predictive abilities of the Resource Utilization Group for home care case-mix system.

Alzheimer’s disease (AD) is a progressive, degenerative neurological disorder for which there is no cure. The causative agent is ?-amyloid (A?) which becomes neurotoxic upon conformational change from ?-helix to ?-sheet. In silico methods have been used to indentify endogenous small molecules of the brain that are capable of binding to A? to inhibit conformational changes; this is a novel approach to the disease. Through the use of computational methods, several small molecules that are endogenous to the brain, such as phosphoserine, have been identified as being capable of binding to the monomeric forms of A?; in vitro studies support their role as anti-aggregants. One of the small molecules identified through these in silico methods, 3-hydroxyanthranilic acid (3HAA) has been developed through the use of Quantitative Structure-Activity Relationship (QSAR) studies to design more potent analogues. These in silico studies have also examined the capacity of synthetic compounds (structurally similar to endogenous molecules) to bind to both A? and other proteins affiliated with AD. Results indicate the potential for a single molecule to bind “promiscuously” to multiple proteins bearing a common BBXB (where B is a basic amino acid) motif affiliated with AD. This will allow for the development of molecules to target AD in a multifaceted approach. Furthermore, these small molecules can be selected through the use of “physinformatics” to bind with equal efficacy to the HHQK and LVFF regions (which play a role in the misfolding process) of A?; this will prevent conformational changes of the protein. A novel diagnostic imaging agent for AD has also been developed through computational methods; solapsone (formerly used to treat leprosy) has been identified as being structurally similar to species that bind to A? to initiate conformational changes. Results show that solapsone can chelate gadolinium, used in MRI, and bind to the soluble forms of A?, allowing for imaging of the toxic species in the human brain, and thus a definitive diagnosis of AD (which is not currently possible with living patients). Computational methods have proved useful in developing a new approach to treating AD, and designing a novel imaging agent.

Senatvei būdinga daug stresą sukeliančių faktorių, kurie gali pabloginti psichikos sveikatą, pvz., mažėjantis funkcinis pajėgumas ir socialinė izoliacija. Taip pat įgimti ar paveldėti žmogaus sveikatos sutrikimai, kurie pasireiškia vyresniame amžiuje. Ilgėjant žmonių gyvenimo trukmei, tampa aktualūs, dažnai pastebimi senatviniai psichikos sutrikimai. Vienas iš senatvinių psichikos sutrikimų yra Alzheimerio liga. Sistemingai didėjant Alzheimerio liga sergančių pacientų skaičiui, atsiranda problema kaip efektyviai padėti šiems žmonėms pagerinti jų gyvenimo kokybę. Socialinių paslaugų teikimas tokiems pacientams, socialiniams darbuotojams tampa svarbi veiklos sritis. Tyrimo tikslas – atskleisti socialinių darbuotojų patirtis dirbant su pacientais, sergančiais Alzheimerio liga. Tyrimo imtis – 6 socialiniai darbuotojai, dirbantys Kauno miesto slaugos ir palaikomojo gydymo ligoninėse. Pirmoje darbo dalyje pateikiama Alzheimerio ligos samprata, jos medicininiai bei psichosocialiniai aspektai; socialinio darbuotojo veiklos ir metodai dirbant su Alzheimerio liga sergančiais pacientais. Antroje darbo dalyje pristatoma atlikto kokybinio tyrimo metodika. Trečioje darbo dalyje pristatomi bei interpretuojami gauti tyrimo duomenys. Tyrimo rezultatai parodė, kad socialiniai darbuotojai, dirbdami su Alzheimerio liga sergančiais pacientais, renka informaciją apie pacientą bei teikia pagalbą palaikant paciento savarankiškumą. Dirbdami su šeima, socialiniai darbuotojai, ne tik gauna... [toliau žr. visą tekstą] / Old age brings many stressors that can worsen mental health, for example, decreasing functional capacity and social isolation. Also, congenital or inherited disorders have influence on human health, which occurs later in life. Senile mental disorders are often observed and have become important because of increasing life expectancy of people. One of senile mental disorders is Alzheimer's disease. The number of patients with Alzheimer’s disease is systematically increasing, so, there is the problem of how to effectively help these people improve their quality of life. Social services for such patients are an important area of activity for social workers. The aim - to reveal the social workers' experience working with patients suffering from Alzheimer's disease. The survey sample - 6 social workers working in Kaunas city nursing hospitals. In the first part of the work there is given the concept of Alzheimer's disease, its medical and psychosocial aspects and social worker's activities and methods of dealing with patients with Alzheimer's disease. The second part presents the methodology of qualitative research which was carried out. The third part presents the results of a study and interpretation of data. The results showed that social workers working with Alzheimer's disease patients collects the information about patient and provide assistance in maintaining the patient's autonomy. Working with families, social workers, not only receives the information about a patient... [to full text]

Focused ultrasound (FUS) can temporarily increase blood-brain barrier (BBB) permeability and locally deliver therapeutic agents to the brain. To date, applications of FUS for treatment of Alzheimer’s disease (AD) have not been explored. Here, I propose that FUS can facilitate a rapid reduction in amyloid-β peptide (Aβ) pathology in a mouse model of AD. Firstly, FUS was used to enhance delivery of an antibody directed against Aβ, which aggregates and forms extracellular plaques. FUS mediated the delivery of antibodies to the targeted right cortex by 4 hours post-treatment and antibodies remained bound to Aβ plaques for 4 days. At 4 days post-treatment, stereological quantification of plaque burden demonstrated a significant reduction of 23%. Secondly, FUS treatment alone resulted in a significant reduction in plaque load (13%). I then investigated effects of FUS that may contribute to Aβ plaque reduction, specifically the delivery of endogenous antibodies to the brain and, activation of microglia and astrocytes. Endogenous immunoglobulin was found bound to plaques within the treated cortex at 4 days post-FUS. Western blot analysis confirmed that immunoglobulin levels were increased significantly. Further, FUS led to a time-dependent increase in glial response. The expression of ionized calcium-binding adaptor molecule 1, a marker of phagocytic microglia, was increased at 4 hours and 4 days, and it was resolved by 15 days. Astrocytes had a slightly delayed response, with an increase in the expression of glial fibrillary acidic protein at 4 days, which declined by 15 days. After 4 days, microglia and astrocytes had significantly greater volumes and surface areas, signifying enhanced activation in the FUS-treated cortex, without an apparent increase in cell count. Co-localization of Aβ within activated glia revealed a significant increase in Aβ internalization following FUS. In conclusion, it was demonstrated that the delivery of exogenous antibodies by FUS, and FUS alone can lead to plaque reduction. Mechanisms by which FUS alone reduces plaque load may include entry of endogenous antibodies to the brain and the induction of a transient glial response. This work details acute effects of FUS that highlight the promise of this delivery method for AD treatment.

No description available.

Impaired attention can hinder information processing at multiple levels and may explain some aspects of the cognitive decline in aging. An inefficient inhibitory system can lead to deficits in focused attention (FA). FA deficits are observed in patients with mild cognitive impairment and Alzheimer’s disease (AD). The Stroop task was applied to functional magnetic resonance imaging (fMRI) to investigate the neural correlates of FA in cognitively normal older adults (NC), patients with amnestic MCI (aMCI) and patients with mild AD. Twenty-one NC, seven aMCI and fifteen mild AD patients performed a verbal Stroop- fMRI paradigm. Both structural and T2*-weighted functional scans were acquired. In Series 0, subjects were presented with colour words printed in black ink and were asked to read the word. In Series 1 and 2, subjects were presented with colour words printed in an incongruent ink colour. Series 1 had four blocks of the ‘Read the word’ condition followed by four blocks of the ‘Say the colour of the ink’ condition. Series 2 had eight blocks of alternating ‘Read the word’ and ‘Say the colour of the ink’ conditions. SPM5 was used to detect anatomical areas with significant signal intensity differences between the two conditions. The NC group performed significantly better in the Stroop-fMRI task than the aMCI and mild AD groups. The percentage of errors on incongruent trials was significantly lower in the NC group (2%) than the aMCI (14%) and mild AD (13%) groups. The ‘Say the colour of the ink’ minus ‘Read the word’ contrast for the NC and mild AD groups yielded common areas of activation in the supplementary motor area, precentral gyrus, and inferior frontal gyrus. aMCI patients also showed activation in the precuneus, temporal and postcentral gyri. Worse performance on the Stroop-fMRI task by the aMCI and mild AD groups suggests deficits in FA. This is the first study to investigate the neural correlates of FA using the Stroop task in aMCI and AD patients. The verbal Stroop-fMRI paradigm employed in the current study provides a means to study the neural correlates of FA in older adult and patient populations. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2009-12-31 11:57:52.374

Patients with dementia are often unaware of their disease and do not seek medical attention; thus, health care providers must shift to "active detection" to identify at-risk patients early. No previous studies have focused on promoting this shift, so this study evaluates the efficacy of a new program to improve the knowledge and confidence of primary care providers in the early detection, diagnosis, and management of mild dementia. Physicians and nurses (n = 38) were recruited from 14 practices in Ontario, Canada. The Mild Dementia Knowledge Transfer Program was run at each practice. As a Neuroscience Master’s student I demonstrated the cognitive assessment procedures, and recipients assessed remaining patients with my guidance. Assessments included patient interviews using a Data Gathering Form –developed for the Program – to provide informal cognitive assessment, and the Montreal Cognitive Assessment (MoCA) test. The procedures were discussed between assessments to enhance learning. Later, recipients discussed the assessment results with the dementia specialist and myself; diagnoses and initial care plans were formulated collaboratively. Questionnaires measuring knowledge and confidence regarding detection, assessment and care of mild dementia were developed to measure change pre-post and three months after the Program. Linear mixed-effects models analysis with time as fixed effect and intercept as random effect was conducted to test change. Program recipients showed increases in knowledge-confidence score after the program (10.3; P < .001) paralleling increases in both knowledge and confidence sub-scores; there was no decline after three months (P = .83). No differences were observed between medical and nursing staff. The number of assessments done by recipients was positively associated with knowledge-confidence change (P = .01). Most recipients (70%) rated the program as excellent; 65% rated interactivity as the best part, 34% rated time commitment as the worst part, and 91% rated the program as making it easier to detect dementia. Due to the complex nature of dementia, the Program was performance-oriented, specialist-supported, clinic-based, and flexible to the needs of recipients. It showed acceptability and feasibility within primary care, and the results support its’ efficacy to improve primary care providers’ self-rated knowledge and confidence in mild dementia care. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2010-07-26 21:38:54.945