Mieux connaitre le pronostic de la démence peut aider à anticiper la prise en charge de la maladie. Au niveau individuel, le besoin d’obtenir de l’information sur les évolutions possibles de la maladie est la première attente des aidants. Au niveau sociétal, d’un point de vue santé publique, il semble nécessaire que les politiques de santé puissent anticiper les besoins en matière de prise en charge, d’aide à domicile, de structure d’accueil, d’équipes spécialisées, de gestionnaires de cas pour les cas complexes. L’objectif général de cette thèse était d’étudier le pronostic des sujets atteints de démence pour améliorer la prise en charge des malades atteints de maladie d’Alzheimer ou de syndromes apparentés. Les travaux de cette thèse ont été réalisés à partir des cas incidents de démence de deux cohortes en population : la cohorte Paquid (Personnes Agées QUID) et la cohorte des Trois Cités. Dans une première partie, nous avons étudié le pronostic de la survie. Globalement, il semble difficile de prédire le décès à partir de facteurs pronostiques seulement liés à la démence. Les décès dans la démence peuvent être liés à la démence elle-même mais aussi à d’autres causes non liées à la démence et sont donc difficiles à prédire. Dans une deuxième partie nous nous sommes intéressés au pronostic des capacités fonctionnelles. Peu de littérature existe sur l’évolution et le pronostic des capacités fonctionnelles. Nous avons montré une hiérarchie de l’atteinte des activités de bases de la vie quotidienne chez les sujets déments avec une atteinte dans un premier temps de la toilette ou de l’habillage puis dans un deuxième temps de la locomotion ou de l’alimentation. D’un point du vue pragmatique, étudier le passage vers l’incapacité à la toilette ou à l’habillage a un réel intérêt pour améliorer la prise en charge des patients. Les facteurs pronostiques indépendants de la survenue d’une incapacité à la toilette ou à l’habillage ajustés sur le risque de décès étaient : un âge supérieur à 80 ans au moment du diagnostic de démence, un diagnostic de démence vasculaire, l’atteinte de trois ou quatre activités sur l’échelle des quatre IADL de Lawton et une santé subjective mauvaise ou très mauvaise au moment du diagnostic de démence. Les travaux de cette thèse nous ont permis de mieux connaitre l’évolution des capacités fonctionnelles dans la démence. Toutefois, il est difficile de prédire l’évolution de la maladie, la démence étant une maladie multi-factorielle pour laquelle il existe une variabilité interindividuelle très importante concernant la progression de la maladie. / A better understanding of the prognosis of dementia could help to provide appropriate care in the disease. At individual level, the need to obtain information on the possible evolution of the disease is caregivers’ prime expectation. At societal level and from a public health point of view, it seems necessary that health policies anticipate needs in care, home care, case managers... The general objective of this thesis was to study the prognosis of dementia to improve the care of patients with Alzheimer's disease or related disorders. We worked from incident cases of dementia of two population-based, long-term cohort studies: Paquid (Personnes Agées QUID) cohort and the Three Cities. First, we studied survival prognosis. Overall, it seems difficult to predict death from only prognostic factors related to dementia. The death in dementia may be linked to dementia itself but also to other factors non-related to dementia and therefore difficult to predict. Secondly, we studied the prognosis of functional abilities. Few literature exists on the functional evolution in dementia. We identified a perfect hierarchy in the sequence of occurrence of total disability in 4 basic activities of daily living: bathing and/or dressing, followed by transferring and/or feeding. From a pragmatic point of view, characterizing the dependency in bathing or dressing is crucial to improve care in dementia. The independent prognosis factors on bathing and dressing disabilities occurrence, adjusted on death risk were: age greater than 80 years at time of diagnosis of dementia, a diagnosis of vascular dementia, disabilities in three or four activities out of the four IADL scale of Lawton and poor or very poor subjective health at time of diagnosis of dementia. Based on this thesis, we have a gained a better knowledge of the evolution of functional abilities in dementia. However, it is difficult to predict the course of the disease; dementia being a multifactorial disease for which there is a very high interindividual variability on the progression of the disease.

Objective: To assess patient reported efficacy of Botulinum toxin type-A for the prophylaxis of migraine headaches in patients with frequent migraine headaches prior to initiation of treatment with Botulinum toxin type-A compared to post treatment. Questions addressed include is there a difference in frequency of migraine headaches following treatment with Botulinum toxin type-A, is there a difference in cost of conventional treatment versus Botulinum toxin type-A and is there a difference in quality of life. Research Plan: Questions addressed patient status prior to the initiation of treatment as well as post treatment. Patient quality of life change, duration and frequency headache improvement are the primary focus. Other considerations included the cost difference between the previous use of other treatment and the periodic treatment with Botulinum toxin type-A. Methodology: A Cross Sectional study utilizing a questionnaire consisting of a modified Migraine Disability Assessment (MIDAS) questionnaire will be given to patients who had received more than one series of injections. Patients who reported chronic migraine headaches and were refractory to previous treatment methods were screened and placed in programs utilizing intramuscular injection of Botulinum toxin type-A at standard points on the face, Temporalis muscle and paracervical muscles. Clinical Relevance: This assessment is relevant to occupational issues due to the increasing number of patients applying for disability due to uncontrolled migraine headaches as well as lost productivity and reduction in functional capacity for activities of daily living. Impact and Significance: Patients that are debilitated by recurrent chronic migraine headaches suffer loss of productive time at work and home. Treatment with Botulinum toxin type-A may results in significant relief allowing fewer days lost at work and improved quality of life. There may be significant cost saving if treatment results in discontinuation of other medications previously used for treatment of migraine headaches. Findings: According to the patients' responses to this survey, it appears that there was an overall improvement in the patients' ability to do work, for those who were employed, as well as their ability to do activities of daily living post treatment with Botulinum toxin-A. Though there were occasionally conflicting data seen in individual cases regarding responses to some of the answers, there appeared to be an overall statistically significant reduction in the mean of responses to the questions. The general implication is consistent with studies that indicate Botulinum toxin-A may be a useful adjunct in the prophylactic treatment of refractory migraine headaches.

Major depressive disorder (MDD) is a relevant condition to consider regarding Work Capacity Evaluation (WCE) because of its high prevalence, strong impact on short-term work disability, and low rate of treatment. The challenge that faces occupational therapists (OTs) is that there is no specific guideline and process to follow when conducting Work Capacity Evaluation with clients suffering from MDD. The researcher had also noted conflicting opinions with regard to the outcome of Work Capacity Evaluation (WCE) and recommendations in occupational therapy reports. The researcher is of the opinion that indeed occupational therapy assessments need to be clear about what to measure, and selection of appropriate standardised measures and non-standardised assessments is needed. Therefore, the research question was, what are the perceptions and practices of occupational therapists in determining work capacity of employees suffering from major depressive disorder? The aim of this study was to describe the perceptions and practices of occupational therapists in determining work capacity of employees suffering from major depressive disorder. The literature showed that Work Capacity Evaluation assists to determine the employee’s returnto- work. The Code of Good Practice: Dismissal contained in the Labour Relations Act of 1998, stipulates that incapacity on the ground of ill health or injury may be either temporary or permanent. The nature of this study was a mixed method design including both qualitative and quantitative approaches. The phenomenological strategy was used. The study had a sample size of 68 participants, practising as occupational therapists. Purposive sampling was used. The data were collected in four distinct phases, referred to as sequential exploratory strategy with elements of embedded design. Phase one, used descriptive open-ended questions; phase two was a close-ended questionnaire to confirm findings in phase one; phase three consisted of focus group interviews and phase four was member checking to confirm findings in phase three. During data analysis, five themes related to employees suffering from MDD emerged and they were identified as: (1) the content of comprehensive assessment for work capacity evaluation, (2) the process of work capacity evaluation, (3) the competency requirements of the occupational therapist, (4) occupational performance and (5) formulating return-to-work decision. Recommendations related to the five themes were formulated and suggestions for future research proffered. The study clarified and confirmed that occupational therapists have a major role to play in performing work capacity of employees suffering from major depressive disorder, and that they need to be competent in performing these evaluations. Copyright / Dissertation (MOccTher)--University of Pretoria, 2011. / Occupational Therapy / unrestricted

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Physical inactivity, a modifiable risk factor for coronary heart disease (CHD) both in persons with intellectual disability (ID) and non-ID, is considered the fourth leading cause of death in the world. Long-term regular participation in physical activity is associated with a reduced risk for CHD. Literature currently lacks evidence on the effect of long-term physical activity on the functional capacity and risk factors for developing CHD in persons with ID. The purpose of this study was firstly, to determine the effect of a long-term physical activity intervention on the risk factors associated with developing CHD and secondly the effect of a combined aerobic and resistance physical activity intervention on the functional capacity of persons with ID. A cohort of seventy-four (74) participants living in a care facility in Potchefstroom, South Africa, participated in this study, a seven-year follow-up physical activity intervention study. To determine the effect of a seven-year combined aerobic and resistance exercise intervention programme, data was collected in 2006 and in 2013. At baseline (2006) and end (2013), a CHD risk profile was determined by means of a questionnaire and physical assessment. The physical assessment included resting blood pressure, peripheral glucose and cholesterol measurements, and body composition by means of body mass index (BMI), waist-to-hip ratio (WHR) and body fat percentage derived from skinfold measurements. Cardiorespiratory fitness was assessed by means of the adapted sub-maximal YMCA bicycle ergometer protocol from which a physical work capacity (PWC) was calculated. The participants followed a structured physical activity intervention two days per week for at least 45 minutes for a seven year period. The exercise intervention consists of cardiorespiratory exercises, muscle stretches and muscle endurance exercises. All data analyses were performed with SPSS 22.0 (IBM SPSS Statistics, Armonk, NY) statistical analysis software programme. The descriptive statistics (mean and standard deviations) as well as frequencies were calculated to describe the characteristics of the participants and the point prevalence of the CHD risk factors. General Linier Model analyses were applied to determine the significant changes in CHD risk factors measured from baseline to end with adjustment for baseline measurements. McNemar exact test indicated significant changes in the point prevalence of the CHD risk factors from baseline to end. The relationship between the changes in the cardiorespiratory fitness and the measured risk factors were performed with a partial correlation analysis adjusting for age in 2013. The level of significance was set at p ≤ 0.05. The results indicate that the prevalence of inactivity decreased with 50% after the seven-year intervention program. Prevalence of age as a risk factor for developing CHD increased significantly post-intervention from 10% to 18%. Body mass decreased significantly in men (1.25 ± 5.43 kg) and increased significantly in women (0.15 ± 6.83kg). BMI changes reflect changes in body mass of the participants. Body fat percentages increased both in men (2.98%) and in women (0.95%). A significant increase in systolic blood pressure (6.2 ± 10.1 mmHg) for men and diastolic blood pressure (6.35 ± 10.42 mmHg) for women was found. Physical work capacity in both male (1.90 ± 0.73 watt/kg) and female (1.55 ± 0.43 watt/kg) participants decreased to 1.43 ± 0.45 watt/kg and 1.14 ± 0.46 watt/kg respectively during the intervention period. Although a correlation between changes in PWC and the risk factors for CHD was found, none of the correlations was significant when adjusted for age in 2013. The conclusion drawn from this study is that a long-term physical activity intervention in a population with ID reduced the point prevalence for physical inactivity and overweight and obesity, in spite of a decrease in cardiorespiratory fitness. The changes in cardiorespiratory fitness did not relate to the changes observed in the risk factors of CHD. / MSc (Biokinetics), North-West University, Potchefstroom Campus, 2015

Physical inactivity, a modifiable risk factor for coronary heart disease (CHD) both in persons with intellectual disability (ID) and non-ID, is considered the fourth leading cause of death in the world. Long-term regular participation in physical activity is associated with a reduced risk for CHD. Literature currently lacks evidence on the effect of long-term physical activity on the functional capacity and risk factors for developing CHD in persons with ID. The purpose of this study was firstly, to determine the effect of a long-term physical activity intervention on the risk factors associated with developing CHD and secondly the effect of a combined aerobic and resistance physical activity intervention on the functional capacity of persons with ID. A cohort of seventy-four (74) participants living in a care facility in Potchefstroom, South Africa, participated in this study, a seven-year follow-up physical activity intervention study. To determine the effect of a seven-year combined aerobic and resistance exercise intervention programme, data was collected in 2006 and in 2013. At baseline (2006) and end (2013), a CHD risk profile was determined by means of a questionnaire and physical assessment. The physical assessment included resting blood pressure, peripheral glucose and cholesterol measurements, and body composition by means of body mass index (BMI), waist-to-hip ratio (WHR) and body fat percentage derived from skinfold measurements. Cardiorespiratory fitness was assessed by means of the adapted sub-maximal YMCA bicycle ergometer protocol from which a physical work capacity (PWC) was calculated. The participants followed a structured physical activity intervention two days per week for at least 45 minutes for a seven year period. The exercise intervention consists of cardiorespiratory exercises, muscle stretches and muscle endurance exercises. All data analyses were performed with SPSS 22.0 (IBM SPSS Statistics, Armonk, NY) statistical analysis software programme. The descriptive statistics (mean and standard deviations) as well as frequencies were calculated to describe the characteristics of the participants and the point prevalence of the CHD risk factors. General Linier Model analyses were applied to determine the significant changes in CHD risk factors measured from baseline to end with adjustment for baseline measurements. McNemar exact test indicated significant changes in the point prevalence of the CHD risk factors from baseline to end. The relationship between the changes in the cardiorespiratory fitness and the measured risk factors were performed with a partial correlation analysis adjusting for age in 2013. The level of significance was set at p ≤ 0.05. The results indicate that the prevalence of inactivity decreased with 50% after the seven-year intervention program. Prevalence of age as a risk factor for developing CHD increased significantly post-intervention from 10% to 18%. Body mass decreased significantly in men (1.25 ± 5.43 kg) and increased significantly in women (0.15 ± 6.83kg). BMI changes reflect changes in body mass of the participants. Body fat percentages increased both in men (2.98%) and in women (0.95%). A significant increase in systolic blood pressure (6.2 ± 10.1 mmHg) for men and diastolic blood pressure (6.35 ± 10.42 mmHg) for women was found. Physical work capacity in both male (1.90 ± 0.73 watt/kg) and female (1.55 ± 0.43 watt/kg) participants decreased to 1.43 ± 0.45 watt/kg and 1.14 ± 0.46 watt/kg respectively during the intervention period. Although a correlation between changes in PWC and the risk factors for CHD was found, none of the correlations was significant when adjusted for age in 2013. The conclusion drawn from this study is that a long-term physical activity intervention in a population with ID reduced the point prevalence for physical inactivity and overweight and obesity, in spite of a decrease in cardiorespiratory fitness. The changes in cardiorespiratory fitness did not relate to the changes observed in the risk factors of CHD. / MSc (Biokinetics), North-West University, Potchefstroom Campus, 2015

A distrofia muscular de Duchenne (DMD) é uma doença hereditária, degenerativa e progressiva dos músculos esqueléticos. É causada pela ausência da proteína distrofina e caracterizada pela perda progressiva da força muscular e deterioração da capacidade funcional. Alterações na regulação da homeostase do cálcio, proteólise e alterações metabólicas, especialmente mitocondriais, são parte da patogênese da doença. A coenzima Q (CoQ10), potente antioxidante que participa da atividade da cadeia respiratória, tem sido utilizada em ensaios clínicos, entretanto, não há estudos que evidencie seu comprometimento na DMD. O objetivo deste estudo foi avaliar a CoQ10 e a da atividade da cadeia respiratória em fragmentos de biópsia muscular de pacientes com DMD e sua correlação com parâmetros clínicos e a capacidade funcional. O estudo constitui de uma etapa retrospectiva, onde foram analisadas 22 biópsias musculares de pacientes com DMD, e outra prospectiva, onde foram avaliados dez pacientes com DMD. Dez pacientes controles foram utilizados nas duas etapas do estudo. A concentração da CoQ10 foi realizada através da técnica de cromatografia líquida de alta performance de fase reversa. As atividades das enzimas da cadeia respiratória foram medidas através de técnicas espectrofotométricas. A capacidade funcional foi mensurada através das escalas Medida da Função Motora (MFM) e Escala de Avaliação para deambulantes North Star (NSAA), e dos testes cronometrados: tempo para percorrer 10 metros (T10), tempo para realizar a manobra de Gowers (TGowers) e teste da caminhada dos 6 minutos (TC6min). Fase retrospectiva: a média de idade dos pacientes com DMD foi de 6,9 anos, (DP ±2,4) e controles de 8 anos, (DP ±2,69). A dosagem média de CoQ10 nos fragmentos de pacientes com DMD foi de 8,6 µg/g de tecido (DP ±3,9) e nos fragmentos dos controles foi de 31,6 µg/g de tecido (DP ±6,9). A média da área ocupada por fibras musculares nos pacientes com DMD foi de 27,3% (DP ±14,2%) e nos controles foi de 89,2% (DP ±3,3%). Evidenciou-se alta correlação entre aquantidade de CoQ10 e a área relativa ocupada por fibras musculares (r= 0,767 e p= 0,016). As atividades dos complexos enzimáticos da cadeia respiratória dos pacientes com DMD não demonstraram deficiência. Já o resultado do ensaio conjunto dos complexos II+III, encontra-se significativamente reduzido nos pacientes com DMD. Etapa prospectiva: a média de idade dos pacientes com DMD foi de 6,5 anos, (DP ±2,4). A dosagem média de CoQ10 nos fragmentos de pacientes com DMD foi de 12,6 µg/g de tecido (DP ±5,1). A média da área ocupada por fibras musculares nos pacientes com DMD foi de 40,3% (DP ±20,4%). Houve alta correlação entre a quantidade de CoQ10 e a área relativa ocupada por fibras musculares (r= 0,690 e p= 0,058). A correlação da dosagem da CoQ10 com os instrumentos de avaliação da capacidade funcional foi alta com o TGowers e moderada com MFM total e dimensões 1 e 2, NSAA, T10 e TC6min. Em relação à área relativa de fibras musculares, houve moderada correlação com a dimensão 1 da MFM e com o TGowers. Não houve correlação da CoQ10 e da área relativa ocupada por fibras musculares com os parâmetros clínicos: idade no momento da biópsia, idade do início dos sintomas e tempo de evolução da doença. No presente estudo, concluímos que existe uma deficiência secundária de CoQ10 em pacientes com DMD, a qual contribui para entender a fisiopatologia da doença e com grande relevância para as propostas terapêuticas. / Duchenne muscular dystrophy (DMD) is a hereditary, degenerative and progressive skeletal muscles disease. It is caused by the absence of the protein dystrophin and characterized by progressive loss of muscle strength and deterioration of functional capacity. Alterations in the regulation of calcium homeostasis, proteolysis and metabolic abnormalities, especially mitochondrial dysfunction, are part of the pathogenesis of the disease. Coenzyme Q (CoQ10), a potent antioxidant that participates in respiratory chain activity, has been used in clinical trials, however, there are no studies showing its involvement in DMD. The purpose of this study was to investigate CoQ10 content and respiratory chain activity in muscle biopsy of patients with DMD and its correlation with clinical parameters and functional capacity. The study consisted of a retrospective phase, in which 22 muscle biopsies from patients with DMD were analyzed, and a prospective phase, where ten patients with DMD were evaluated. The same control group of ten patients were used in the two phases of the study. The concentration of CoQ10 was measured using the reverse phase high performance liquid chromatography technique. Activities of the respiratory chain enzymes were measured by spectrophotometry. The functional capacity was evaluated using the Motor Function Measurement (MFM) and North Star Ambulatory Assessment (NSAA) and the following timed tests: to run 10 meters (T10), to perform the Gowers maneuver (TGowers) and the 6-minute walk test (6MWT). Retrospective phase: the mean age of patients with DMD was 6.9 years (SD ± 2.4) and of controls was 8 years (SD ± 2.69). The mean CoQ10 content in fragments from patients with DMD was 8.6 ?g / g tissue (DP ± 3.9) and in fragments from controls was 31.6 ?g / g tissue (DP ± 6.9). The mean area occupied by muscle fibers in patients with DMD was 27.3% (SD ± 14.2%) and in controls was 89.2% (SD ± 3.3%). There was a high correlation between the amount of CoQ10 and the relative area occupied by muscle fibers (r= 0.767 and p= 0.016). The activities of respiratory chain enzymes from patients with DMD were not deficient. On the other hand, the results of the combined analysis of complexes II + III were significantly reduced in patients with DMD. Prospective phase: the mean age of patients with DMD was 6.5 years (SD ± 2.4). The mean CoQ10 content in fragments from patients with DMD was 12.6 ?g / g tissue (SD ± 5.1). The mean area occupied by muscle fibers in patients with DMD was 40.3% (SD ± 20.4%). There was a high correlation between the amount of CoQ10 and the relative area occupied by muscle fibers (r= 0.690 and p= 0.058). The correlation between the amount of CoQ10 and the functional capacity assessment instruments was high forTGowers and moderate for MFM total and dimensions 1 and 2, NSAA, T10 andd TC6min. Regarding the relative area of muscle fibers, there was a moderate correlation with MFM dimension 1 (standing position and transfers) and TGowers. There was no correlation between CoQ10 and relative area occupied by muscle fibers with clinical parameters: age at time of biopsy, age of onset of symptoms and time of disease progression. In the present study, we conclude that there is a secondary deficiency of CoQ10 in patients with DMD, which contributes for the understanding of its physiopathology and is relevant for therapy.