No description available.

Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta. The mechanism by which these DA neurons die is still unclear and under investigation. Although mostly idiopathic, about 10% of PD cases have shown familial inheritance. Mutations in leucine-rich repeat kinase 2 (LRRK2), a large multi-domain protein with unknown physiological and pathological roles, have been linked to PD cases of autosomal dominant inheritance. A PD Drosophilamelanogaster model over expressing the human LRRK2(I2020T) kinase mutant using the GAL4/UAS system has shown a loss of DA neurons and locomotor deficiency. Additionally, ectopic overexpression of human LRRK2 in the eye caused a damaged eye phenotype characterized by roughness of the surface, loss of pigmentation and presence of black lesions (Venderova Ket. al., 2009). The presence of this identifiable eye phenotype has allowed us to perform a suppressor/enhancer screen to identify possible genetic interactors of LRRK2. The LRRK2(I2020T) transgenic flies were crossed with genomic deficiency lines and the eye phenotype screened for either suppression or enhancement. Twenty-two genes, which are implicated in a variety of biological processes, have been identified thus far. Fourteen of these 22 interacting genes were assessed in the DA neurons of the D.melanogaster model. This functional screen is a rapid method to provide us with potential genetic interactions between LRRK2 and other genes, which will in turn, aid in elucidating the functional role of LRRK2 in PD pathology.

Parkinson’s disease (PD) is a neurodegenerative movement disorder and a leading cause of neurological disability in the older adult population. Historically, the research and treatment of PD has focused on the associated motor symptoms. Now the non-motor symptoms such as sleep disturbance are becoming an increased focus for researchers. Deep brain stimulation (DBS) is a surgical intervention that has proven to be beneficial for PD motor symptom management. There are claims from the literature that DBS may assist with the phenomenon of sleep disturbance. A case study analysis was done to explore this concept in the DBS-PD patient population using the framework of the Symptom Management Theory. From the analysis of the subjective and objective data gathered it is clear that the phenomenon of sleep disturbance in this population is multifaceted and that DBS may play a role in managing the phenomenon of sleep disturbance for this population.

The purpose of this study was to determine if a ten week, twice weekly group exercise program using large amplitude movement and functional mobility training was effective at improving mobility and quality of life in old, older adults (i.e. average age 80 years) with Parkinson’s disease (PD). This exercise program builds on existing large amplitude movement training programs, but differs in that it is delivered in a group format, in an older cohort and incorporates functional training related to the tasks of daily living. To determine the long term training effects of the program, a follow up assessment was conducted at four months post intervention. Sixteen participants with PD with an average age of 80 years (range 69-91years) were recruited through a hospital-based Seniors Outpatient Clinic. Participants were assessed before starting (PRE) and upon completion (POST) of the intervention. To decrease the likelihood that the results would be affected by day-to-day fluctuations in mobility that are often seen with PD, 3 measures were gathered at both PRE and POST and then averaged to provide a single PRE and POST score. A single follow-up assessment was conducted four months after completion. Outcome measures included: Movement Disorder Society-Unified Parkinson’s Disease Rating Scale-Part III, Timed Up and Go, Berg Balance Scale, Sit-to-stand Test, gait characteristics (GaitRite system), Parkinson’s Disease Questionnaire – 39 and Goal Attainment Scale. Results indicate significant improvements from PRE to POST (p≤0.05) in all measures of physical function (effect sizes (ES) ranging from 0.35-0.87), Quality of Life (QOL) (mobility dimension, ES=0.34) and personal goal achievement (ES=2.12). Therefore this group exercise program was effective in improving mobility and QOL for an older adult population with PD. The program frequency and duration was adequate to achieve the desired training effects while being manageable for an old, older population to attend. Further, in those participants who continued to engage in ongoing physical activity, improvements were maintained at 4 months after completion of the program for MDS-UPDRS, TUG, gait velocity, QOL (bodily discomfort dimension) and GAS. / Graduate / 0382 / gallagher_karla@yahoo.ca

Dopamine (DA) is a key catecholamine neurotransmitter involved in motor control, cognition, and neuroendocrine regulation. Reduced DA transmission is associated with Parkinson’s disease, depression, and anhedonia. An overexpression of the dopamine transporter in mice (DAT-tg) results in a 40% reduction in extracellular DA, and can be classified as a genetic model of hypodopaminergia. Reserpine treatment depletes extracellular DA, and is a pharmacological model of hypodopaminergia. The aim of this study was to determine morphological and proteomic changes to medium spiny neurons (MSNs), which receive dopaminergic input, as a consequence of reduced DA transmission. To achieve this, MSNs were fluorescently labelled using a diolistics method and immunofluorescence. There were no observable changes to morphology or proteomic profile of MSNs in DAT-tg animals. Reserpine treatment resulted in reduced spine density in MSNs. DAT-tg animals may present a level of DA depletion that is below the threshold to induce morphological changes to MSNs.

Objectives: To estimate the incremental cost per QALY in patients with Parkinson’s Disease (PD) with varying disease severity and to ascertain which patient subgroup would accrue the greatest net monetary benefits to Ontario’s public health perspective as a result of Deep Brain Stimulation (DBS). Design: A cost-utility study and a net monetary benefit framework approach were applied to 37 PD patients with varying disease stages who underwent DBS treatment. Results: DBS resulted in cost savings of $2,686.3, $2,752.4, and $7348.4 and QALY gains of 0.33, 0.09 and 0.04 in patients with mild, moderate and severe PD. The ICER was $16,076.2/QALY. At $50,000/QALY, the greatest net monetary benefits accrued to Ontario’s MOHLTC were from treating patients with mild PD with DBS. Conclusions: DBS surgery was found to be a cost-effective PD treatment compared to pharmacotherapy. The greatest net monetary benefits were from treating patients with mild PD severity.

Dopamine (DA) is a key catecholamine neurotransmitter involved in motor control, cognition, and neuroendocrine regulation. Reduced DA transmission is associated with Parkinson’s disease, depression, and anhedonia. An overexpression of the dopamine transporter in mice (DAT-tg) results in a 40% reduction in extracellular DA, and can be classified as a genetic model of hypodopaminergia. Reserpine treatment depletes extracellular DA, and is a pharmacological model of hypodopaminergia. The aim of this study was to determine morphological and proteomic changes to medium spiny neurons (MSNs), which receive dopaminergic input, as a consequence of reduced DA transmission. To achieve this, MSNs were fluorescently labelled using a diolistics method and immunofluorescence. There were no observable changes to morphology or proteomic profile of MSNs in DAT-tg animals. Reserpine treatment resulted in reduced spine density in MSNs. DAT-tg animals may present a level of DA depletion that is below the threshold to induce morphological changes to MSNs.

Objectives: To estimate the incremental cost per QALY in patients with Parkinson’s Disease (PD) with varying disease severity and to ascertain which patient subgroup would accrue the greatest net monetary benefits to Ontario’s public health perspective as a result of Deep Brain Stimulation (DBS). Design: A cost-utility study and a net monetary benefit framework approach were applied to 37 PD patients with varying disease stages who underwent DBS treatment. Results: DBS resulted in cost savings of $2,686.3, $2,752.4, and $7348.4 and QALY gains of 0.33, 0.09 and 0.04 in patients with mild, moderate and severe PD. The ICER was $16,076.2/QALY. At $50,000/QALY, the greatest net monetary benefits accrued to Ontario’s MOHLTC were from treating patients with mild PD with DBS. Conclusions: DBS surgery was found to be a cost-effective PD treatment compared to pharmacotherapy. The greatest net monetary benefits were from treating patients with mild PD severity.

It is well established that there are many intrinsic and extrinsic risk factors associated with falls in older adults. Less well-known is what risk factors predict falls in more vulnerable populations, such as those with neurological conditions living in long-term care homes or receiving home care services. Furthermore, evidence comparing those with neurological conditions to those without is lacking in the literature. The primary purpose of this thesis was to determine risk factors for falls in long-term care residents and home care clients with no recent history of falls to determine if risk factors differed between individuals with dementia or Parkinson’s disease and those without any neurological conditions. Secondary data analysis was performed on a database of standardized health assessments completed for long-stay home care clients and long-term care residents in Ontario. Within each major diagnostic group, observations were stratified based on ambulatory status (ambulatory vs. non-ambulatory). Bivariate analyses followed by generalized estimating equations were used to determine statistically significant predictors of falls in each group within each care setting. The results of multivariable analyses showed that there is not a distinct set of risk factors associated with falls in home care clients and long-term care residents with dementia or Parkinson’s disease that is systematically different from risk factors associated with falls in clients and residents not diagnosed with any of the neurological conditions in this study. These results suggest that a common set of risk factors may effectively predict falls in all clients and residents with no recent falls history, regardless of certain neurological diagnoses.

Psychopharmacological studies have implicated the mesolimbic dopamine (DA) system in the mediation of cost/benefit evaluations about effort-related costs associated with larger rewards. However, the role of DA in risk-based decision making remains relatively unexplored. The present study investigated how systemic manipulations of DA transmission affect risky choice assessed with a probabilistic discounting task. Over discrete trials, rats between two levers; a press on the “small/certain” lever always delivered one reward pellet, whereas a press on the other, “large/risky” lever delivered four pellets, but the probability of receiving reward decreased across the four trial blocks (100%, 50%, 25%, 12.5%). In separate groups of well-trained rats we assessed the effects of the DA releaser amphetamine, as well as receptor selective agonists and antagonists. Amphetamine consistently increased preference for the large/risky lever; an effect that was blocked or attenuated by co-administration of either D₁ (SCH23390) or D₂ (eticlopride) receptors antagonists. Blockade of either of these receptors alone induced risk aversion. Conversely, stimulation of D₁ (SKF81297) or D₂ (bromocriptine) receptors also increased risky choice. In contrast, activation of D₃ receptors with PD128,907 induced risk aversion. Likewise, D₃ antagonism with nafadotride potentiated the amphetamine-induced increase in risky choice. Blockade or stimulation of D₄ receptors did not reliably alter patterns of choice. These findings indicate that DA plays a critical role in mediating risk-based decision making, where increased activation of D₁ and D₂ receptors biases choice towards larger, probabilistic rewards, whereas D₃ receptors appear to exert opposing effects on this form of decision making.