This phenomenological study was designed to explore and describe the experience of older women who are caring for husbands with Parkinson's disease. The study was conducted with a sample of seven caregivers ranging in age from 50 -74 years who had lived with husbands with Parkinson's disease for 9-38 years. Data were collected by intensive interviewing usually at the home of the caregiver. The data were analyzed for common themes. The findings revealed that each wife experienced three phases during the course of caregiving. The three phases were: coping with illness, taking over, and separating life paths. These phases occurred in relation to the changes due to the illness, that each wife perceived in her husband, her marriage and herself. Each phase developed as the disease progressed and was meaningful to each wife because of her personal perceptions. Understanding the nature of caregiving in this way may help health care workers to provide more appropriate support for caregivers. Implications for practice are discussed. / Applied Science, Faculty of / Nursing, School of / Graduate

The kynurenine pathway plays a critical role in regulating immunological homeostasis in the brain. Evidence supporting the hypothesis that kynurenine pathway dysfunction may exacerbate progression of neurodegenerative diseases like Parkinson’s is growing. First, we investigate the effects of Interferon-γ, Lipopolysaccharide, and Interleukin-4 on several key kynurenine pathway metabolites using high performance liquid chromatography. We found that Interferon-γ had significant effects on the extracellular concentration of kynurenine metabolites in astrocytes, microglia, and macrophage. GCSF gene therapy is previously demonstrated to exert neuroprotective effects on models of Parkinson’s and Alzheimer’s disease. Seven days after receiving GCSF gene therapy, A53T Parkinson’s mice were found to have increased levels of GCSF and tyrosine hydroxylase positive neurons. A concurrent increase in expression of the kynurenine pathway enzyme kynurenine aminotransferase 2 was observed. GCSF gene therapy may exhibit neuroprotective effects in a Parkinson’s disease mouse model by restoring this key kynurenine pathway enzyme. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2021. / FAU Electronic Theses and Dissertations Collection

No description available.

- / -

Thesis (doctoral)--University of Lund, 1995. / Added t.p. with thesis statement inserted.

Thesis (Ph. D.)--Virginia Commonwealth University, 2009. / Prepared for: Dept. of Physiology. Bibliography: leaves 171-206. Also available online via the Internet.

Thesis (doctoral)--University of Lund, 1995. / Added t.p. with thesis statement inserted.

nÃo hà / O trabalho avalia em duas fases as alteraÃÃes clÃnicas, alteraÃÃes do sono, a alteraÃÃo cognitiva e as alteraÃÃes de estruturas cerebrais atravÃs de RessonÃncia MagnÃtica (RM) e morfologia baseada em voxel (VBM) em pacientes com DoenÃa de Parkinson. Foram estudados 100 pacientes (71% masculino), com idade entre 40 e 80 anos (66,1+9,5), recrutados do AmbulatÃrio de DistÃrbios do Movimento do Hospital UniversitÃrio Walter CantÃdio. A amostra faz parte de uma coorte longitudinal (Sleep-For-PD study). Foram estudadas as alteraÃÃes do sono e seus fatores associados e preditivos. A escala de sono da DoenÃa de Parkinson (PDSS) que avalia alteraÃÃes de sono na DP, a escala Pittsburgh Sleep Quality Index (PSQI) que avalia a qualidade do sono, a escala Epworth Sleepiness Scale (ESS) que avalia o grau subjetivo de sonolÃncia e a escala Unified Parkinsonâs Disease Scale (UPDRS partes I, II, III e IV) que avalia a gravidade da doenÃa foram estudados. Os sintomas depressivos foram avaliados atravÃs das escalas Beck Depression Inventory (BDI-II) e Hospital Anxiety Depression (HAD). Os pacientes foram submetidos ao Mini Exame do Estado Mental (MEEM) que avaliou o grau de alteraÃÃo cognitiva e a escala de distÃrbio comportamental do sono REM (RBD). A dose de levodopa (DEL) foi avaliada. Pacientes com alteraÃÃes do sono (PDSS) apresentaram mais alucinaÃÃes diurnas, mais alteraÃÃo cognitiva, mais ansiedade, depressÃo e maior gravidade dos sintomas parkinsonianos (p<0,05). Pacientes com mà qualidade de sono (PSQI) tiveram mais sintomas depressivos. Os escores PDSS correlacionaram-se ainda com a funÃÃo cognitiva (MEEM), os sintomas depressivos (BDI e HAD), a qualidade do sono (PSQI), a gravidade da doenÃa e com a escala de RBD. Os escores PSQI correlacionaram-se com o MEEM, atividades de vida diÃria (UPDRS II) e sintomas de depressÃo/ansiedade (BDI e HAD). Gravidade de sintomas relacionados a atividades da vida diÃria (p=0,002), sintomas depressivos (p=0,01) e ansiedade (p=0,01) foram fatores independentes preditivos das alteraÃÃes do sono (PDSS). A DEL e o MEEM foram preditores da mà qualidade do sono (p=0,02). A escala RBD (p=0,002) e a UPDRS I (p=0,02) foram preditores do grau de sonolÃncia. ConcluÃmos que alteraÃÃes de sono, mà qualidade de sono e sonolÃncia diurna excessiva sÃo comuns na DP. As escalas PDSS, PSQI e ESS tÃm fatores associados e preditivos distintos. A escala PDSS apresenta maior abrangÃncia na avaliaÃÃo do sono na DP. Na segunda fase, foram avaliadas as estruturas cerebrais por RM, a presenÃa de alteraÃÃes cognitivas e fatores associados em 39 pacientes com DP e em 10 indivÃduos controles pareados por idade. As imagens de RM foram processadas de acordo com o protocolo para processamento de VBM. A variÃvel de desfecho usada foi o volume de substÃncia cinzenta. Nossos dados evidenciaram que pacientes com DP apresentaram maior comprometimento cognitivo e maior ansiedade. Pacientes com DP e alteraÃÃes cognitivas apresentaram maior gravidade da doenÃa. NÃo houve diferenÃa no volume de substÃncia cinzenta entre os pacientes com DP com e sem alteraÃÃes cognitivas. Estes achados provavelmente deveram-se a atrofia cerebral precoce nos pacientes cognitivamente intactos. Pacientes com DP, quando comparados aos controles, revelaram reduÃÃes de volume de substÃncia cinzenta na Ãnsula esquerda e cÃrtex prÃ-frontal esquerdo, demonstrando envolvimento assimÃtrico do cÃrebro na DP. / The present study evaluates clinical abnormalities, sleep disturbances, cognitive alterations and structural brain changes using Magnetic Resonance Imaging (MRI) with Voxel Based Morphometry (VBM) in patients with Parkinson`s Disease (PD). In the first phase of the study one hundred patients (71% male), aged between 40 and 80 years (66,1+9,5) were studied. Patients were recruited from a movement disorders clinics at Walter CantÃdio University Hospital. The study is part of a larger longitudinal cohort study (Sleep-For-PD study). Sleep abnormalities and their associated and predictive factors were scrutinized. Many clinical questionnaires were used, including the Parkinson`s Disease Sleep Scale (PDSS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and the Unified Parkinsonâs Disease Rating Scale (UPDRS part I, II, III e IV). Depressive symptoms were evaluated with Beck Depression Inventory (IDB-II) and Hospital Anxiety Depression scale (HAD). The Minimental state examination (Folstein) (MMSE) evaluated the extent of cognitive dysfunction. REM sleep symptoms were evaluated by the REM Sleep Behavior Disorder (RBD) Scale. The levodopa equivalent dose was evaluated (DEL). Patients with sleep abnormalities (PDSS) had more diurnal visual hallucinations, cognitive dysfunction, anxiety, depression and worse parkinsonian symptoms (p<0.05). Patients with worse sleep quality (PSQI) had more depressive symptoms. PDSS scores were correlated with cognitive function (MEEM), depressive symptoms (BDI and HAD), sleep quality (PSQI), severity of PD and the RBD scale. PSQI scores were correlated with MMSE scores, activity of daily living symptoms (UPDRS II) and depression / anxiety (BDI e HAD). Activities of daily living (p=0.002), depressive symptoms (p=0.01) and anxiety (p=0.01) were independent predictors of sleep abnormalities (PDSS). The levodopa equivalent dose and MMSE scores were independent predictors of worse sleep quality (p=0.02). The RBD scale (p=0.002) and UPDRS I (p=0.02) were independent predictors of somnolence. We conclude that sleep disorders, disturbed sleep quality and excessive diurnal somnolence are common in PD. The PDSS, PSQI and ESS scales have distinct associated and predictive factors. PDSS scale is associated with a greater number of factors in PD patients. In the second phase of the study thirty-nine PD patients and ten control subjects were evaluated with regard to the presence of cognitive alterations. Structural brain abnormalities were also evaluated with MRI and VBM technique. The Gray matter volume was used as the ending variable. PD patients had more cognitive impairment and more anxiety. Patients with PD and cognitive alterations had worse disease severity. We found no difference in the volume of gray matter between the subgroups of PD patients with and without cognitive alterations, probably due to early brain atrophy in the patients without cognitive abnormalities. A significant reduction in gray matter volume in the left insula and left prefrontal cortex was observed when comparing PD patients in relation to controls. These findings indicate an asymmetrical brain involvement in PD, the left hemisphere being more affected.

Parkinson's disease is an incurable, progressive neurodegenerative brain disorder. Individuals living with Parkinson's disease often face considerable challenges in managing the progressive decline of their symptoms and maintaining their quality of life (Broadfoot et al., 2019). During the progression of PD, 75-90% of individuals will have a speech and voice disorder (National Center for Voice and Speech, 2019). The communication disorder most commonly associated with PD is hypokinetic dysarthria (HKD). Many individuals with PD may have significant difficulty communicating and participating effectively in a variety of speaking situations due to their communication deficits (Dykstra et al., 2015). Addressing an individuals perceived quality of communication and their perceived communication effectiveness should be an essential target during intervention due to the implications it has on the psychological well-being and prognosis for people with PD. Participants in this study were recruited from individuals previously diagnosed with Parkinson's disease attending the SPEAK OUT! & LOUD Crowd® program. The research questions included (1) Does the implementation of the SPEAK OUT! ® and the LOUD Crowd® program have a positive effect on participants’ perceived quality of communication (PQOC), and (2) Do these programs have a significant positive effect on participants perceived communicative effectiveness (PCE)? The Voice Handicap Index (VHI) and the Communicative Effectiveness Survey- Revised (CESR®) were utilized in this research study. The surveys were administered prior to the SPEAK OUT!® training and following the completion of this portion of the program. They were administered every 16 weeks while the participant was in the LOUD Crowd® training during the duration of this project. It was hypothesized that participants' PQOC related to their voice and their PCE will improve following the implementation of this program. Due to COVID-19 restrictions, results from this study only considered baseline scores and post-test 1 scores following the completion of the SPEAK OUT!® program. The results from this study support the hypothesis that the SPEAK OUT!® program has a positive effect on the participants’ PQOC. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2021. / FAU Electronic Theses and Dissertations Collection

Parkinson disease (PD) is an incurable disease, second only to Alzheimer’s disease as the most common neurodegenerative disease in adults. Unfortunately, the course of disease is significantly longer for individuals diagnosed at an early age (20-40 years of age). Although early-onset, recessively inherited cases represent a small subset of individuals with PD (~5- 10%), their clinical presentation is unique, with symptoms being almost exclusively motor-related. The expressivity of early-onset PD is partially explained by post-mortem neuropathological findings, which demonstrate a specific loss of dopamine synthesizing cells in brainstem nuclei that also produce neuromelanin (i.e. Substantia nigra and Locus coeruleus). With the majority of early-onset PD cases being caused by homozygous and biallelic heterozygous mutations in the PRKN gene, its gene product, parkin, has been extensively studied. It is generally accepted that loss of its E3 ligase function leads to neurodegeneration by either one of the following two mechanisms: i) toxic substrate accumulation from the loss of target protein ubiquitination (and related degradation), or ii) accumulation of dysfunctional mitochondria due to impaired mitophagy initiation. However, whether these mechanisms lead to selective neuronal loss within the human brain remains unknown. This thesis represents a body of work that supports a novel role for parkin as a thiol-based anti-oxidant and redox homeostasis regulator, which helps explain the cell-specificity observed in recessive, PRKN-linked PD. These findings include: i) evidence that human brain parkin uniquely and natively undergoes age-associated aggregation beginning at 40 years of age (Chapter 2); ii) identification of multiple, reversible and irreversible oxidative modifications of parkin cysteines, both in cells and tissues, including dopamine-adduct conjugation on primate sequence-specific cysteine 95 (Chapter 2); iii) the demonstration that irreversible oxidation of parkin cysteines causes aggregate formation ii in cells and mice exposed to exogenous and/or endogenous sources of oxidative and dopamine stress (Chapter 2 and 3); iv) evidence that parkin functions as a thiol-dependent anti-oxidant similar to glutathione (Chapter 2), which lowers oxidation state in cells and tissues under native and stress conditions (Chapter 2 and 3); v) the demonstration that parkin cysteines, notably C95, directly bind glutathione and regulate glutathione redox homeostasis in cells and tissues in a dynamic fashion (Chapter 3); and vi) the development of novel, human-specific, anti-parkin monoclonal antibodies that preferentially detect oxidized and aggregated forms of parkin found associated with neuromelanin and lysosomal storage vesicles within neurons of human Substantia nigra (Chapter 2 and 4). Future studies focusing on further validation of in situ oxidative modifications of parkin cysteines and their effect on protein structure, notably the poorly studied linker region that contains C95, will provide insight into how these oxidative modifications affect the function of parkin in vivo, including in adult human brain. Also, identifying the bona fide intracellular redox partners of parkin will be crucial to understanding how this protein regulates cellular redox state. Of clinical importance, the findings presented here indicate a potential, human-specific link between parkin and neuromelanin formation, which deserves to be further explored, such as with parkin mouse models engineered to produce neuromelanin. Finally, designing clinical trials using anti-oxidants specifically in individuals affected by PRKN-associated PD represents a logical, translational treatment approach to explore.