Sarcopenia na doença de Parkinson: avaliação clínica, risco de quedas e protocolo de reabilitação

Detalhes bibliográficos
Ano de defesa: 2021
Autor(a) principal: Lima, Danielle Pessoa
Orientador(a): Braga Neto, Pedro
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/62945
Resumo: Parkinson's Disease (PD) is the second most prevalent neurodegenerative disease in Brazil, present in about 1% of the elderly over 65 years of age and between 4 to 5% in those over 85 years of age. It is a chronic, progressive, and disabling disorder, with motor and non-motor symptoms, compromising quality of life. Genetic factors, oxidative stress, environmental toxins, and mitochondrial abnormalities are involved in its pathophysiology. The parkinsonian syndrome consists of four cardinal signs: resting tremor, muscle rigidity, akinesia or bradykinesia, and postural instability. Bradykinesia is a required feature for the diagnosis accompanied by one more sign. Sarcopenia is a complex and multifactorial condition characterized by reduced quantity and/or quality of skeletal muscle tissue. The pathophysiology of sarcopenia has elements in common with PD and involves mitochondrial dysfunction, increased oxidative stress, inflammation, imbalance in protein metabolism (greater degradation than synthesis). In sarcopenia, other determining factors are decrease in hormones and growth factors and proteins that maintain adequate cell functions, decline in essential nutrient intake, decline in physical activity. Most of these contributors are not unique to the muscular system, they can also apply to the nervous system. It is common in PD, and severe sarcopenia is diagnosed in 1 out of 5 parkinsonian patients. Power training (PT) is a more effective intervention than strength training in gait performance and risk of falls. Elastic bands and tubes are simple tools for PT, allowing you to work all major muscle groups. This thesis consisted of evaluating the prevalence of sarcopenia in PD and its repercussions, developing a protocol of PT and, subsequently, investigating its viability in this population. A cross-sectional study was carried out at the Movement Disorders Outpatient Clinic in Fortaleza, Brazil, where 218 patients with PD were evaluated, of which 121 (55.5%) were classified as possible sarcopenic by SARC-F and 103 (47.4%) as likely probable sarcopenics. Sarcopenia was associated with worse quality of life and falls. A “PARK-BAND” intervention protocol was developed, a randomized, single-blind, unicentric, two-arm parallel study for 12 weeks, which will include 50 participants with PD, with the purpose of evaluating the potential benefits of PT, using elastic devices. Participants will be randomized in a 1:1 ratio to the PT group and the health education group (HEG). The primary outcomes will be the bradykinesia score from the Unified Parkinson's Disease Rating Scale motor exam and the functional physical performance, assessed by the Short Physical Performance Battery. The HEG will receive a booklet with 12 chapters with strategies to live well with the disease (1x/week, 50-60 minutes). The PT is based on fast movements with low resistance loads, the movement being as fast as possible in the concentric phase and slower in the eccentric phase (2x/week, 50-60 minutes). It is required to complete at least 85% of the planned sessions. Feasibility study of this protocol was carried out. Thirty-four patients were screened at telephone recruitment to include 8 eligible, of which 5 (62.5%) were women with a median age of 66 (45-77) years. The attendance rate to the HEG was 83.3% and to the PT 96.82%, the adherence rate to the HEG was 80% and to the PT 95.23%, the retention rate was 75% in both groups, no adverse events. Sarcopenia has many pathophysiological changes in common with a PD. Sarcopenia will lead to functional loss and falls. Optimizing muscle function is essential to improve quality of life, risk of falling, and motor symptoms of bradykinesia. Based on these results, we intend to validate the criteria for confirmed sarcopenia in PD and carry out the PARK-BAND study. Based on these results, we intend to validate the criteria for confirmed sarcopenia in PD, validate the booklet and carry out the Park-Band study.
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spelling Lima, Danielle PessoaSobreira Neto, Manoel AlvesBraga Neto, Pedro2021-12-13T15:49:08Z2021-12-13T15:49:08Z2021-12-03LIMA, D. P. Sarcopenia na doença de parkinson: avaliação clínica, risco de quedas e protocolo de reabilitação. 2021. 237 f. Tese (Doutorado em Ciências Médicas) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2021. Disponível em: http://www.repositorio.ufc.br/handle/riufc/62945. Acesso em: 13/12/2021.http://www.repositorio.ufc.br/handle/riufc/62945Parkinson's Disease (PD) is the second most prevalent neurodegenerative disease in Brazil, present in about 1% of the elderly over 65 years of age and between 4 to 5% in those over 85 years of age. It is a chronic, progressive, and disabling disorder, with motor and non-motor symptoms, compromising quality of life. Genetic factors, oxidative stress, environmental toxins, and mitochondrial abnormalities are involved in its pathophysiology. The parkinsonian syndrome consists of four cardinal signs: resting tremor, muscle rigidity, akinesia or bradykinesia, and postural instability. Bradykinesia is a required feature for the diagnosis accompanied by one more sign. Sarcopenia is a complex and multifactorial condition characterized by reduced quantity and/or quality of skeletal muscle tissue. The pathophysiology of sarcopenia has elements in common with PD and involves mitochondrial dysfunction, increased oxidative stress, inflammation, imbalance in protein metabolism (greater degradation than synthesis). In sarcopenia, other determining factors are decrease in hormones and growth factors and proteins that maintain adequate cell functions, decline in essential nutrient intake, decline in physical activity. Most of these contributors are not unique to the muscular system, they can also apply to the nervous system. It is common in PD, and severe sarcopenia is diagnosed in 1 out of 5 parkinsonian patients. Power training (PT) is a more effective intervention than strength training in gait performance and risk of falls. Elastic bands and tubes are simple tools for PT, allowing you to work all major muscle groups. This thesis consisted of evaluating the prevalence of sarcopenia in PD and its repercussions, developing a protocol of PT and, subsequently, investigating its viability in this population. A cross-sectional study was carried out at the Movement Disorders Outpatient Clinic in Fortaleza, Brazil, where 218 patients with PD were evaluated, of which 121 (55.5%) were classified as possible sarcopenic by SARC-F and 103 (47.4%) as likely probable sarcopenics. Sarcopenia was associated with worse quality of life and falls. A “PARK-BAND” intervention protocol was developed, a randomized, single-blind, unicentric, two-arm parallel study for 12 weeks, which will include 50 participants with PD, with the purpose of evaluating the potential benefits of PT, using elastic devices. Participants will be randomized in a 1:1 ratio to the PT group and the health education group (HEG). The primary outcomes will be the bradykinesia score from the Unified Parkinson's Disease Rating Scale motor exam and the functional physical performance, assessed by the Short Physical Performance Battery. The HEG will receive a booklet with 12 chapters with strategies to live well with the disease (1x/week, 50-60 minutes). The PT is based on fast movements with low resistance loads, the movement being as fast as possible in the concentric phase and slower in the eccentric phase (2x/week, 50-60 minutes). It is required to complete at least 85% of the planned sessions. Feasibility study of this protocol was carried out. Thirty-four patients were screened at telephone recruitment to include 8 eligible, of which 5 (62.5%) were women with a median age of 66 (45-77) years. The attendance rate to the HEG was 83.3% and to the PT 96.82%, the adherence rate to the HEG was 80% and to the PT 95.23%, the retention rate was 75% in both groups, no adverse events. Sarcopenia has many pathophysiological changes in common with a PD. Sarcopenia will lead to functional loss and falls. Optimizing muscle function is essential to improve quality of life, risk of falling, and motor symptoms of bradykinesia. Based on these results, we intend to validate the criteria for confirmed sarcopenia in PD and carry out the PARK-BAND study. Based on these results, we intend to validate the criteria for confirmed sarcopenia in PD, validate the booklet and carry out the Park-Band study.A Doença de Parkinson (DP) é a segunda doença neurodegenerativa mais prevalente no Brasil, presente em cerca de 1% dos idosos com mais de 65 anos e de 4 a 5% daqueles com mais de 85 anos. Ela é uma desordem crônica, progressiva e incapacitante, com sintomas motores e não-motores, comprometendo a qualidade de vida. Fatores genéticos, estresse oxidativo, toxinas ambientais e anormalidades mitocondriais estão envolvidos na sua fisiopatologia. A síndrome parkinsoniana consiste em quatro sinais cardinais: tremor de repouso, rigidez muscular, acinesia ou bradicinesia e instabilidade postural, sendo a bradicinesia obrigatória acompanhada de mais um dos sinais. Sarcopenia é uma condição complexa e multifatorial caracterizada por redução da quantidade e qualidade do tecido muscular esquelético. A fisiopatologia da sarcopenia tem elementos em comum com a DP e envolve: disfunção mitocondrial, elevação de estresse oxidativo, inflamação, desequilíbrio no metabolismo das proteínas (degradação superior à síntese, além de diminuição de hormônios e de fatores de crescimento e de proteínas que mantêm funções celulares adequadas, declínio na ingestão de nutrientes essenciais, declínio em atividade física. A maioria destes contribuintes não são exclusivos do sistema muscular, eles também podem ser aplicáveis ao sistema nervoso. A sarcopenia é comum na DP, e a sarcopenia grave é diagnosticada em 1 de cada 5 pacientes parkinsonianos. O treinamento de força potente (TFP) é uma intervenção mais efetiva do que o treinamento de força no desempenho da marcha e no risco de quedas. As faixas e tubos elásticos são ferramentas simples para o TFP, permitindo trabalhar todos os grandes grupos musculares. Esta tese consistiu em avaliar a prevalência de sarcopenia na DP e de suas repercussões, elaborar um protocolo de intervenção de força potente e, posteriormente, averiguar sua viabilidade nesta população. Foi realizado um estudo transversal no Ambulatório de Transtornos do Movimento, em Fortaleza, Brasil, onde foram avaliados 218 pacientes com DP, dos quais 121 (55,5%) foram classificados como possíveis sarcopênicos pelo SARC-F e 103 (47,4%) como prováveis sarcopênicos. A sarcopenia esteve associada com pior qualidade de vida e quedas. Foi elaborado um protocolo de intervenção “PARK BAND”, estudo randomizado, simples-cego, unicêntrico, com dois braços em paralelo de 12 semanas, que incluirá 50 participantes com DP, com o objetivo de investigar os potenciais benefícios do TFP, utilizando dispositivos elásticos. Os participantes serão randomizados numa proporção de 1:1 para o grupo de TFP e para o grupo de educação em saúde (GES). Os desfechos primários serão a pontuação da bradicinesia, pelo exame motor da Unified Parkinson's Disease Rating Scale e pelo desempenho físico funcional, avaliada pelo Short Physical Performance Battery. O GES receberá uma cartilha com 12 capítulos com estratégias para viver bem com a doença (1x/semana, 50-60 minutos). O TFP baseia-se em movimentos rápidos com cargas de baixa resistência, sendo o movimento o mais rápido possível na fase concêntrica e mais lento na fase excêntrica (2x/semana, 50-60 minutos), devendo completar no mínimo 85% das sessões planejadas. Foi realizado estudo de viabilidade deste protocolo. Foram triados 34 pacientes no recrutamento telefônico para incluir 8 elegíveis, dos quais 5 (62,5%) eram mulheres com mediana de idade de 66 (45-77) anos. A taxa de comparecimento ao GES foi de 83,3% e ao TFP 96,82%, a taxa de aderência ao GES foi de 80% e ao TFP 95,23%, a taxa de retenção foi de 75% em ambos os grupos, sem eventos adversos. A sarcopenia tem muitas alterações fisiopatológicas em comum com a DP. É fundamental otimizar a função muscular para melhorar a qualidade de vida, o risco de cair e os sintomas motores de bradicinesia. A partir destes resultados, pretende-se validar os critérios de sarcopenia confirmada na DP e executar o estudo PARK-BAND.Doença de ParkinsonSarcopeniaIdosoTranstornos ParkinsonianosSarcopenia na doença de Parkinson: avaliação clínica, risco de quedas e protocolo de reabilitaçãoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessORIGINAL2021_tese_dplima.pdf2021_tese_dplima.pdfapplication/pdf5181446http://repositorio.ufc.br/bitstream/riufc/62945/1/2021_tese_dplima.pdfdeac1f211fbab810f26aa059a30d6ce5MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/62945/3/license.txt8a4605be74aa9ea9d79846c1fba20a33MD53riufc/629452021-12-13 12:50:19.993oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2021-12-13T15:50:19Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Sarcopenia na doença de Parkinson: avaliação clínica, risco de quedas e protocolo de reabilitação
title Sarcopenia na doença de Parkinson: avaliação clínica, risco de quedas e protocolo de reabilitação
spellingShingle Sarcopenia na doença de Parkinson: avaliação clínica, risco de quedas e protocolo de reabilitação
Lima, Danielle Pessoa
Doença de Parkinson
Sarcopenia
Idoso
Transtornos Parkinsonianos
title_short Sarcopenia na doença de Parkinson: avaliação clínica, risco de quedas e protocolo de reabilitação
title_full Sarcopenia na doença de Parkinson: avaliação clínica, risco de quedas e protocolo de reabilitação
title_fullStr Sarcopenia na doença de Parkinson: avaliação clínica, risco de quedas e protocolo de reabilitação
title_full_unstemmed Sarcopenia na doença de Parkinson: avaliação clínica, risco de quedas e protocolo de reabilitação
title_sort Sarcopenia na doença de Parkinson: avaliação clínica, risco de quedas e protocolo de reabilitação
author Lima, Danielle Pessoa
author_facet Lima, Danielle Pessoa
author_role author
dc.contributor.co-advisor.none.fl_str_mv Sobreira Neto, Manoel Alves
dc.contributor.author.fl_str_mv Lima, Danielle Pessoa
dc.contributor.advisor1.fl_str_mv Braga Neto, Pedro
contributor_str_mv Braga Neto, Pedro
dc.subject.por.fl_str_mv Doença de Parkinson
Sarcopenia
Idoso
Transtornos Parkinsonianos
topic Doença de Parkinson
Sarcopenia
Idoso
Transtornos Parkinsonianos
description Parkinson's Disease (PD) is the second most prevalent neurodegenerative disease in Brazil, present in about 1% of the elderly over 65 years of age and between 4 to 5% in those over 85 years of age. It is a chronic, progressive, and disabling disorder, with motor and non-motor symptoms, compromising quality of life. Genetic factors, oxidative stress, environmental toxins, and mitochondrial abnormalities are involved in its pathophysiology. The parkinsonian syndrome consists of four cardinal signs: resting tremor, muscle rigidity, akinesia or bradykinesia, and postural instability. Bradykinesia is a required feature for the diagnosis accompanied by one more sign. Sarcopenia is a complex and multifactorial condition characterized by reduced quantity and/or quality of skeletal muscle tissue. The pathophysiology of sarcopenia has elements in common with PD and involves mitochondrial dysfunction, increased oxidative stress, inflammation, imbalance in protein metabolism (greater degradation than synthesis). In sarcopenia, other determining factors are decrease in hormones and growth factors and proteins that maintain adequate cell functions, decline in essential nutrient intake, decline in physical activity. Most of these contributors are not unique to the muscular system, they can also apply to the nervous system. It is common in PD, and severe sarcopenia is diagnosed in 1 out of 5 parkinsonian patients. Power training (PT) is a more effective intervention than strength training in gait performance and risk of falls. Elastic bands and tubes are simple tools for PT, allowing you to work all major muscle groups. This thesis consisted of evaluating the prevalence of sarcopenia in PD and its repercussions, developing a protocol of PT and, subsequently, investigating its viability in this population. A cross-sectional study was carried out at the Movement Disorders Outpatient Clinic in Fortaleza, Brazil, where 218 patients with PD were evaluated, of which 121 (55.5%) were classified as possible sarcopenic by SARC-F and 103 (47.4%) as likely probable sarcopenics. Sarcopenia was associated with worse quality of life and falls. A “PARK-BAND” intervention protocol was developed, a randomized, single-blind, unicentric, two-arm parallel study for 12 weeks, which will include 50 participants with PD, with the purpose of evaluating the potential benefits of PT, using elastic devices. Participants will be randomized in a 1:1 ratio to the PT group and the health education group (HEG). The primary outcomes will be the bradykinesia score from the Unified Parkinson's Disease Rating Scale motor exam and the functional physical performance, assessed by the Short Physical Performance Battery. The HEG will receive a booklet with 12 chapters with strategies to live well with the disease (1x/week, 50-60 minutes). The PT is based on fast movements with low resistance loads, the movement being as fast as possible in the concentric phase and slower in the eccentric phase (2x/week, 50-60 minutes). It is required to complete at least 85% of the planned sessions. Feasibility study of this protocol was carried out. Thirty-four patients were screened at telephone recruitment to include 8 eligible, of which 5 (62.5%) were women with a median age of 66 (45-77) years. The attendance rate to the HEG was 83.3% and to the PT 96.82%, the adherence rate to the HEG was 80% and to the PT 95.23%, the retention rate was 75% in both groups, no adverse events. Sarcopenia has many pathophysiological changes in common with a PD. Sarcopenia will lead to functional loss and falls. Optimizing muscle function is essential to improve quality of life, risk of falling, and motor symptoms of bradykinesia. Based on these results, we intend to validate the criteria for confirmed sarcopenia in PD and carry out the PARK-BAND study. Based on these results, we intend to validate the criteria for confirmed sarcopenia in PD, validate the booklet and carry out the Park-Band study.
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-12-13T15:49:08Z
dc.date.available.fl_str_mv 2021-12-13T15:49:08Z
dc.date.issued.fl_str_mv 2021-12-03
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dc.identifier.citation.fl_str_mv LIMA, D. P. Sarcopenia na doença de parkinson: avaliação clínica, risco de quedas e protocolo de reabilitação. 2021. 237 f. Tese (Doutorado em Ciências Médicas) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2021. Disponível em: http://www.repositorio.ufc.br/handle/riufc/62945. Acesso em: 13/12/2021.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/62945
identifier_str_mv LIMA, D. P. Sarcopenia na doença de parkinson: avaliação clínica, risco de quedas e protocolo de reabilitação. 2021. 237 f. Tese (Doutorado em Ciências Médicas) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2021. Disponível em: http://www.repositorio.ufc.br/handle/riufc/62945. Acesso em: 13/12/2021.
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