Efeito do exercício físico resistido como tratamento na fase inicial e avançada da doença de Alzheimer
Arquivos
Data
2024-07-15
Autores
Silva, Eduardo Alves da 
Orientadores
Arida, Ricardo Mario
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A doença de Alzheimer (DA) representa uma condição neurodegenerativa que impacta funções relacionadas à memória e cognição, com prevalência maior em mulheres. As principais áreas afetadas incluem o hipocampo e o córtex pré-frontal, onde ocorre produção de beta amiloide (βA). Dada a presença de déficits cognitivos significativos e a falta de um tratamento totalmente eficaz para a DA, a atividade física regular tem se destacado como uma abordagem complementar para prevenir ou retardar a progressão da doença. Apesar de diversos estudos em humanos e animais indicarem que o exercício aeróbio induz alterações substanciais no cérebro, o impacto do exercício físico resistido (ER) na DA ainda não está completamente esclarecido. Objetivo: O propósito deste estudo foi verificar as alterações comportamentais e moleculares induzidas pelo ER em camundongos fêmea transgênicos para a DA na fase inicial e avançada da doença. Material e Métodos: Foram utilizados camundongos fêmea, distribuídos em 8 grupos: Controle/Controle, Controle/Exercício Alzheimer/Controle (sem treinamento) e Alzheimer/Exercício adultos e idosos submetidos a protocolo de treinamento resistido por quatro semanas. A mobilidade foi avaliada pelo teste de campo aberto, o comportamento do tipo ansioso foi realizado pelo o teste de labirinto em cruz elevado. A memória de longo prazo (MLP) foi avaliada pela tarefa de reconhecimento de objetos e esquiva inibitória. O comportamento do tipo depressivo foi avaliado pelo teste de suspensão pela cauda. A quantificação de peptídeos βA no hipocampo e de citocinas circulantes foi realizada pela técnica de ELISA. Resultados: Nossos resultados mostraram que houve aumento progressivo na força de ambos grupos treinados nas diferentes idades. O genótipo e o exercício aumentaram a ambulação dos animais adultos e dos animais idosos com DA. O ER reverteu o déficit de memória observado nos animais adultos com DA, entretanto, esse resultado não ocorreu nos animais idosos. O ER nos animais adultos produziu uma resposta adaptativa ao estresse ou uma maior disposição para investigar ambientes confinados e nos animais idosos, o ER reverteu o comportamento tipo ansioso observado nos animais com DA. O comportamento do tipo deprimido observados em animais adultos e idosos com DA foi revertido pelo programa de ER. O ER reduziu os peptídeos βA somente nos animais adultos com DA. O ER não teve um impacto notável na memória aversiva nos animais adultos e idosos. Conclusão: Na fase inicial da DA, o ER reduziu a produção de peptídeos βA e a expressão de TNF-α, IL-6, IL-10 e IL1-α. Além disso, o ER reverteu o déficit de memória, e reverteu o quadro de depressão. Nos animais na fase avançada, o ER não apresentou redução dos níveis de βA e não reverteu o déficit de memória, indicando que seu efeito é mais limitado. No entanto, o ER mostrou-se eficaz na redução da ansiedade e do comportamento do tipo depressivo.
Objectives. To develop a new hip arthropathy CT-based severity score (Hip Arthropathy Computed Tomography Score in axial Spondyloarthritis-HACTSAS). Correlate HACTSAS, along with with two other well-known radiographic scores (Bath Ankylosing Spondylitis Radiology Index-BASRI-h and Kellgren-Lawrence score) with hip pain, range of motion (ROM), clinical scores, with the sagittal spine-pelvic-leg alignment (SSPL) patients with axial spondyloarthritis (AS). Secondarily, correlate flexion and extension ROM, and Thomas test with SSPL parameters. Methods. Consecutive patients classified as having AS were included in this study. According to an adaptation of the method by Turmezei et al., HACTSAS was scored considering joint space width (JSW), osteophytes, and subchondral cysts/erosions visualized on the CT scan. First, the correlation of HACTSAS with pain, ROM, and clinical scores was compared to two other well-known radiographic scores, the BASRI-h and Kellgren-Lawrence (KL), in the entire sample, and in subsets with less than 10 years and more than 10 years of symptoms. Clinical scores included in the analysis were related to disease activity (Bath Ankylosing Spondylitis Disease Activity Index-BASDAI, Ankylosing Spondylitis Activity Score-ASDAS), quality of life (Ankylosing Spondylitis Quality of Life questionnaire-ASQoL), functional status (Bath Ankylosing Spondylitis Functional Index-BASFI), and mobility (Bath Ankylosing Spondylitis Metrology Index-BASMI). In the second stage, the 3 radiological scores were correlated with the SSPL parameters (thoracic kyphosis, lumbar lordosis, vertical sagittal axis-SVA, acoustic meatus plumb line-AMpl, pelvic incidence, sacral slope-SS, pelvic tilt-PT, and knee flexion-KF). Finally, for our secondary objective, flexion and extension ROM were correlated with SSPL parameters. Results. The final sample included 112 patients, with a mean age and disease duration of 51.0±11.2 years and 20.9±9.6 years, respectively. HACTSAS, BASRI-h, and KL exhibited excellent interobserver agreement (ICC=0.89, ICC=0.82, ICC=0.89, respectively). HACTSAS (ρ = 0.18, 95% CI = 0.01, 0.33), BASRI-h (ρ = 0.27, 95% CI = 0.11, 0.42), and KL (ρ = 0.23, 95% CI = 0.07, 0.38) showed a weak positive correlation with pain. HACTSAS (ρ = -0.41, 95% CI = -0.54, -0.26), BASRI-h (ρ = -0.44, 95% CI = -0.57, -0.30), and KL (ρ = -0.40, 95% CI = -0.53, -0.25) exhibited a moderate negative correlation with total ROM. Regarding the subsets, the correlations of the 3 radiological scores with pain and ROM were only maintained in the group of patients with more than 10 years of disease. The linear regression model based on HACTSAS was able to explain 33% of the variation in total ROM, 28% in abduction, 22% in flexion, and 20% in internal rotation, while for the BASRI-h, these values were 32%, 26%, 18%, and 24%, respectively. Regarding clinical scores, HACTSAS correlated moderately positively with BASMI in the entire sample (ρ = 0.45, 95% CI = 0.33, 0.55) and in the two subsets, while this correlation was weak for the BASRI-h (ρ = 0.34, 95% CI = 0.22, 0.46) and KL (ρ = 0.36, 95% CI = 0.23, 0.47). HACTSAS (ρ = 0.25, 95% CI = 0.12, 0.38), BASRI-h (ρ = 0.16, 95% CI = 0.02, 0.29), and KL (ρ = 0.18, 95% CI = 0.05, 0.31) had a weak correlation with the functional score (BASFI), but not with ASQol, BASDAI, or ASDAS. In the second stage, HACTSAS, BASRI-h, and KL demonstrated a statistically significant weak correlation with SVA (ρpartial = 0.29, ρpartial = 0.20, and ρpartial = 0.20, respectively) and pMA (ρpartial = 0.22, ρpartial = 0.20, and ρpartial = 0.22, respectively). Hip ROM in extension correlated weakly with SS (ρ = 0.36) and moderately with PT (ρ = -0.42). ROM in extension also correlated moderately with SVA (ρ = -0.51), pMA (ρ = -0.45), and KF (ρ = -0.44). TT had a weak association with ESV (ρ = -0.26) and knee flexion (KF) posture (ρ = 0.36). Conclusion. The new adapted three-dimensional tomographic score for hip arthropathy in patients with AS (HACTSAS) demonstrated similar reproducibility and correlation with pain, ROM, and functionality (BASFI) compared to the BASRI-h and KL radiographic scores but showed a superior correlation with mobility (BASMI). HACTSAS, BASRI-h, and KL correlated with anterior sagittal malalignment (ESV and/or pMA). Furthermore, there was a moderate correlation of ROM in extension and weak correlation of Thomas test to anterior sagittal misalignment (ESV and/or pMA) and knee flexion posture. However, these associations did not affect quality of life in this specific population.
Objectives. To develop a new hip arthropathy CT-based severity score (Hip Arthropathy Computed Tomography Score in axial Spondyloarthritis-HACTSAS). Correlate HACTSAS, along with with two other well-known radiographic scores (Bath Ankylosing Spondylitis Radiology Index-BASRI-h and Kellgren-Lawrence score) with hip pain, range of motion (ROM), clinical scores, with the sagittal spine-pelvic-leg alignment (SSPL) patients with axial spondyloarthritis (AS). Secondarily, correlate flexion and extension ROM, and Thomas test with SSPL parameters. Methods. Consecutive patients classified as having AS were included in this study. According to an adaptation of the method by Turmezei et al., HACTSAS was scored considering joint space width (JSW), osteophytes, and subchondral cysts/erosions visualized on the CT scan. First, the correlation of HACTSAS with pain, ROM, and clinical scores was compared to two other well-known radiographic scores, the BASRI-h and Kellgren-Lawrence (KL), in the entire sample, and in subsets with less than 10 years and more than 10 years of symptoms. Clinical scores included in the analysis were related to disease activity (Bath Ankylosing Spondylitis Disease Activity Index-BASDAI, Ankylosing Spondylitis Activity Score-ASDAS), quality of life (Ankylosing Spondylitis Quality of Life questionnaire-ASQoL), functional status (Bath Ankylosing Spondylitis Functional Index-BASFI), and mobility (Bath Ankylosing Spondylitis Metrology Index-BASMI). In the second stage, the 3 radiological scores were correlated with the SSPL parameters (thoracic kyphosis, lumbar lordosis, vertical sagittal axis-SVA, acoustic meatus plumb line-AMpl, pelvic incidence, sacral slope-SS, pelvic tilt-PT, and knee flexion-KF). Finally, for our secondary objective, flexion and extension ROM were correlated with SSPL parameters. Results. The final sample included 112 patients, with a mean age and disease duration of 51.0±11.2 years and 20.9±9.6 years, respectively. HACTSAS, BASRI-h, and KL exhibited excellent interobserver agreement (ICC=0.89, ICC=0.82, ICC=0.89, respectively). HACTSAS (ρ = 0.18, 95% CI = 0.01, 0.33), BASRI-h (ρ = 0.27, 95% CI = 0.11, 0.42), and KL (ρ = 0.23, 95% CI = 0.07, 0.38) showed a weak positive correlation with pain. HACTSAS (ρ = -0.41, 95% CI = -0.54, -0.26), BASRI-h (ρ = -0.44, 95% CI = -0.57, -0.30), and KL (ρ = -0.40, 95% CI = -0.53, -0.25) exhibited a moderate negative correlation with total ROM. Regarding the subsets, the correlations of the 3 radiological scores with pain and ROM were only maintained in the group of patients with more than 10 years of disease. The linear regression model based on HACTSAS was able to explain 33% of the variation in total ROM, 28% in abduction, 22% in flexion, and 20% in internal rotation, while for the BASRI-h, these values were 32%, 26%, 18%, and 24%, respectively. Regarding clinical scores, HACTSAS correlated moderately positively with BASMI in the entire sample (ρ = 0.45, 95% CI = 0.33, 0.55) and in the two subsets, while this correlation was weak for the BASRI-h (ρ = 0.34, 95% CI = 0.22, 0.46) and KL (ρ = 0.36, 95% CI = 0.23, 0.47). HACTSAS (ρ = 0.25, 95% CI = 0.12, 0.38), BASRI-h (ρ = 0.16, 95% CI = 0.02, 0.29), and KL (ρ = 0.18, 95% CI = 0.05, 0.31) had a weak correlation with the functional score (BASFI), but not with ASQol, BASDAI, or ASDAS. In the second stage, HACTSAS, BASRI-h, and KL demonstrated a statistically significant weak correlation with SVA (ρpartial = 0.29, ρpartial = 0.20, and ρpartial = 0.20, respectively) and pMA (ρpartial = 0.22, ρpartial = 0.20, and ρpartial = 0.22, respectively). Hip ROM in extension correlated weakly with SS (ρ = 0.36) and moderately with PT (ρ = -0.42). ROM in extension also correlated moderately with SVA (ρ = -0.51), pMA (ρ = -0.45), and KF (ρ = -0.44). TT had a weak association with ESV (ρ = -0.26) and knee flexion (KF) posture (ρ = 0.36). Conclusion. The new adapted three-dimensional tomographic score for hip arthropathy in patients with AS (HACTSAS) demonstrated similar reproducibility and correlation with pain, ROM, and functionality (BASFI) compared to the BASRI-h and KL radiographic scores but showed a superior correlation with mobility (BASMI). HACTSAS, BASRI-h, and KL correlated with anterior sagittal malalignment (ESV and/or pMA). Furthermore, there was a moderate correlation of ROM in extension and weak correlation of Thomas test to anterior sagittal misalignment (ESV and/or pMA) and knee flexion posture. However, these associations did not affect quality of life in this specific population.
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Citação
SILVA, Eduardo Alves da. Efeito do exercício físico resistido como tratamento na fase inicial e avançada da doença de Alzheimer. 2024. 100 f. Tese (Doutorado em Neurologia - Neurociências) – Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP). São Paulo, 2024.