INTRODUCTION: Il existe peu d’évidences sur l’association entre le taux de chômage dans le milieu résidentiel (CR) et le risque de maladies cardiovasculaires parmi les résidents de milieux urbains. De plus, on ne sait pas si ce lien diffère entre les deux sexes. Cette thèse a pour objectif de déterminer la direction et la taille de l’association entre le CR et le risque de maladies cardiovasculaires, et d’examiner si cette association varie en fonction du sexe. MÉTHODES: Un sous-échantillon de 342 participants de l’Étude sur les habitudes de vie et la santé dans les quartiers montréalais a rapporté ses habitudes de vie et sa situation socio-économique. Des mesures biologiques et anthropométriques ont été recueillies par une infirmière. Le CR a été opérationnalisé en fonction d’une zone-tampon d’un rayon de 250 m centrée sur la résidence de chacun des participants à l’aide d’un Système d’Information Géographique (SIG). Des équations d’estimation généralisées ont été utilisées afin d’estimer l’association entre le CR et l’Indice de Masse Corporelle (IMC) et un score cumulatif de Risque Cardio-métabolique (RC) représentant la présence de valeurs élevées de cholestérol total, de triglycérides, de lipoprotéines de haute densité et d’hémoglobine glyquée. RÉSULTATS: Après ajustement pour l’âge, le sexe, le tabagisme, les comportements de santé et le statut socio-économique, le fait de vivre dans un endroit classé dans le 3e ou 4e quartile de CR était associé avec un IMC plus élevé (beta pour Q4 = 2.1 kg/m2, IC 95%: 1.02-3.20; beta pour Q3 = 1.5 kg/m2, IC 95%: 0.55-2.47) et un taux plus élevé de risque cardiovasculaires Risque Relatif [RR pour Q4 = 1.82 (IC 95 %: 1.35-2.44); RR pour Q3 = 1.66 (IC 95%: 1.33-2.06)] par rapport au 1er quartile. L'interaction entre le sexe et le CR révèle une différence absolue d’IMC de 1.99 kg/m2 (IC 95%: 0.00-4.01) et un risque supérieur (RR=1.39; IC 95%: 1.06-1.81) chez les femmes par rapport aux hommes. CONCLUSIONS: Le taux de chômage dans le milieux résidentiel est associé à un plus grand risque de maladies cardiovasculaires, mais cette association est plus prononcée chez les femmes. / INTRODUCTION: Little is known about whether area-level unemployment is independently associated with individual-level Cardiovascular Disease (CVD) in an urban setting. Furthermore, it is unclear whether this relationship differs by sex. This thesis examined the direction and magnitude of the association between area-level unemployment (ALU) and Body Mass Index (BMI) and a marker for CVD risk, and whether this association differs by sex. METHODS: A sample of 342 individuals from the Montreal Neighbourhood Survey of Lifestyle and Health (MNSLH) self-reported behavioural and socioeconomic information. A registered nurse collected biochemical and anthropometric data. ALU was operationalised within a 250 m radius buffer centered on individual residence using a Geographic Information System (GIS). Generalized Estimating Equations were used to determine if body mass index (BMI), and a cumulative score for total cardiometabolic risk (TCR) representing elevated values for total cholesterol, triglycerides, high-density lipoprotein cholesterol, and glycosylated hemoglobin, were associated with ALU. RESULTS: After adjustment for age, gender, smoking status, behavioural, and socioeconomic covariates, living in an area in the upper ALU quartiles was associated with an elevated BMI [Q4 beta = 2.1 kg/m2 (95% CI: 1.02-3.20)] and greater TCR [Q4 RR = 1.82 (95 % CI: 1.35-2.44); Q3 RR = 1.66 (95% CI: 1.33-2.06)] relative to the 1st quartile. Sex-by-ALU interaction revealed a 1.99 kg/m2 (95% CI: 0.00-4.01) difference in BMI and 1.39-fold (95% CI: 1.06-1.81) greater TCR Score for women compared to men. CONCLUSIONS: Area-level unemployment is associated with greater CVD risk in men and women but associations are stronger among women.

Titre : Étude des déterminants psychosociaux du poids corporel dans la population québécoise adulte. Objectif : L’objectif principal des travaux effectués était l'étude des déterminants psychosociaux du poids corporel dans quatre groupes d’adultes qui ont participé à l’Enquête sociale et de santé 1998 (ESS 98). Méthodologie : Les microdonnées de l'ESS 98 ont été accédées en utilisant les services de l’Institut de la statistique du Québec. Les groupes étudiés étaient les hommes et les femmes âgés entre 25 et 44 ans ou 45 et 64 ans. Résultats : La pratique d’activités physiques reliées au transport et un niveau de scolarité plus élevé ont été associés à moins de probabilités de rapporter un excès de poids chez les hommes âgés entre 25 et 44 ans. Une meilleure perception des habitudes alimentaires a aussi été associée à moins de probabilités d’avoir un excès de poids dans la plupart des groupes à l’exception des femmes âgées entre 25 et 44 ans. Le niveau d’AP a été associé négativement à l’excès de poids uniquement chez les femmes plus âgées. Une meilleure perception de l’état de santé a été associée à moins de probabilités de rapporter un excès de poids chez les femmes âgées entre 25 et 44 ans et à plus de probabilités chez les hommes âgés entre 45 et 64 ans. Chez les hommes des deux groupes, le tabagisme a été associé à moins de probabilités de rapporter avoir un excès de poids. Chez les femmes, la consommation d’alcool a été associée à moins de probabilités d’avoir un excès de poids. Dans tous les groupes, tenter présentement de perdre du poids a été associé à plus de probabilités de rapporter un excès de poids. Les travaux effectués démontrent que ces déterminants du poids corporel ne sont pas nécessairement associés aux habitudes alimentaires et au niveau d’AP. Conclusion : Les déterminants psychosociaux associés à l’obésité divergent selon le sexe et l’âge. L’identification de ces associations illustre le besoin d’intégrer les spécificités de chacun de ces groupes dans les interventions populationnelles qui visent la problématique du poids corporel. / Title: Psychosocial correlates of body weight in the Quebec Adults Population. Objective: Within the variables available in the 1998 Social and Health survey, identify psycho-social correlates of body mass index (BMI) in the Quebec population. Method: Access to the Social Lifestyles and Health 1998 survey was done at the «Institut de la Statistique du Québec». Groups studied included the 25- to 44-years and the 45- to 64- years old men and women. Results: Higher number of physical activity (PA) related to transport and levels of education were associated with less odds of reporting an excess body weight only in the 25- to 44-years old men. Cigarette smoking was also associated with less odds of reporting an excess weight in both men groups. Regular practice of leisure time PA was associated with less odds of reporting an excess weight only in 45- to 64-years old women. In both women groups, more frequent consumption of alcoholic beverages decreased the odds of reporting an excess weight. Perceived eating habits were also associated with less odds of an excess weight in most groups except in the 25- to 44-yearsold women where the trend was not significant. Opposite associations were observed between perceived health and BMI. In the 45- to 64-year old men, better perceived health increased the odds of reporting an excess weight. On the opposite, the odds of reporting an excess weight decreased with better health in 25- to 44-years-old women. In all groups, currently trying to loose weight increased the odds of reporting an excess weight. Others analyses also indicate that those correlates are not always associated with eating habits and PA level as it would be expected. Conclusion: Many correlates differ between age-group and sex. The identification of these factors illustrates the need to adapt obesity related program toward specific sub-group within the general population.

More than half of all cases of breast cancer occur among women without any known risk factors. More research is needed on suspected risk factors in order to refine current breast cancer screening tools. The objectives of this thesis were: to determine the breast cancer risk associated with known risk factors (ethnicity, family history, breast biopsy, age at menarche, age at first birth, alcohol, HRT, and BMI), suspected risk factors (smoking, second-hand smoke exposure, smoked/grilled foods, and NSAID use), and to examine the above associations according to tumour receptor status, histologic grade, and menopausal status, with potential confounders also considered. This thesis project was conducted within the framework of the Molecular Epidemiology of Breast Cancer study, a case-control study of women in Vancouver, BC and Kingston, ON, with 1140 cases and 1169 controls recruited from 2005-2010. Information was collected from a detailed questionnaire. Cases and controls were similar in terms of age at menarche, age at first birth, smoking history, second-hand smoke exposure, lifetime smoked/grilled food consumption, HRT, and BMI. Among cases, there were significantly less Europeans and more Chinese, Japanese, and Filipino subjects compared to controls. Cases were more likely to have a first degree relative with breast cancer, as well as a previous benign breast biopsy. Alcohol consumption and past NSAID usage was higher among controls. The level of education completed was higher among controls. Cases were also more likely to be postmenopausal. Family history was associated with breast cancer risk (OR=1.59, CI=1.30-1.94), as was BMI (OR=1.28, CI=1.05-1.58 for overweight and OR=2.28, CI=1.35-3.86 for obese class II). Second-hand smoke was also found to be associated with breast cancer risk (OR=1.42, CI=1.02-1.97 for individuals with a less than 10 pack-year smoking history). Due to reduced sample size with stratification and marginally significant results, it is not possible to draw definitive conclusions regarding pathology sub-types. In summary, these results provide support for the association between several risk factors and breast cancer risk. More research is needed to ascertain how receptor status, histologic grade, and menopausal status affect these associations. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2011-08-15 19:43:06.689

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Umeå : Umeå universitet, 2005. / Härtill 5 uppsatser.

Thesis (M.S.)--Uniformed Services University of the Health Sciences, 2005. / Typescript (photocopy).

Thesis (Ph. D.)--Uniformed Services University of the Health Sciences, 2005. / Typescript (photocopy).

Fundamentos: São necessárias avaliações do estado nutricional de povos indígenas, como forma de mensurar influências ambientais e sociais sobre as condições de vida e saúde e fornecer subsídios para intervenções. Este estudo, de base escolar, objetivou descrever o estado nutricional de crianças e adolescentes Kaingang pela antropometria e pela impedância bioelétrica (IBE) e comparar as classificações geradas pelos dois métodos. Métodos: Estudaram-se 3207 indígenas (73,6% dos matriculados) das 35 escolas de 12 Terras Indígenas Kaingang do Rio Grande do Sul, Brasil. Foram mensurados peso e estatura conforme WHO (1995) e parâmetros de resistência (R) e reactância (Xc), em Ohm, mediante impedanciômetro RJL Systems Electrode Placement. O índice estatura/idade e o índice de massa corporal/idade foram calculados e classificados segundo WHO (2007). A composição corporal foi avaliada pela Análise Vetorial de Impedância Bioelétrica (BIVA) conforme Piccoli et al (1994). A comparação entre classificações da antropometria e BIVA foi realizada graficamente, com base nas elipses de tolerância do gráfico RXc. Foram considerados significantes valores de p<0,05. Resultados: A idade média da amostra foi de 10,8 anos (+2,9), sendo 56,8% adolescentes e 50,6% do sexo masculino. Encontraram-se prevalências de déficit estatural (E/I) de 15,5% e 19,9% e de excesso de peso pelo IMC/Idade de 5,7% e 6,7%, respectivamente para crianças e adolescentes. Para ambos os sexos e faixas etárias, a amostra apresentou desvio em direção ao quadrante inferior esquerdo do gráfico RXc, indicando maior proporção de gordura em relação ao tecido não gordo. Para as crianças do sexo masculino a proporção de indivíduos além da elipse de tolerância de 95% foi de 2,7% e a proporção de indivíduos com classificações discrepantes, relativas à antropometria, foi de 94,6%. As mesmas proporções alcançaram, respectivamente, 2,3% e 77,1% para os adolescentes do sexo masculino; 2,5% e 85,4% para as crianças do sexo feminino e 0,6% e 94,8% para as adolescentes do sexo feminino. Conclusão: Aponta-se a transição nutricional entre os Kaingang, caracterizada por prevalências importantes de déficit estatural e excesso de peso. As discrepâncias entre as classificações do IMC/idade e BIVA sinalizam a necessidade de estudos que procurem conciliar maior número de técnicas de avaliação nutricional, como a conciliação da antropometria com a IBE. / Background: Indigenous nutritional status evaluations are necessary, as a way to measure social and environmental influences on health and life conditions and to provide subsidies for interventions. This school-based study aimed to describe the nutritional status of Kaingang children and adolescents by anthropometry and bioelectrical impedance (BIA), and to compare classifications obtained by both methods. Methods: 3207 indigenous (73.6% of the enrolled) of the 35 schools in 12 Indigenous Lands Kaingang of Rio Grande do Sul, Brazil were studied. Weight and height were measured according to WHO (1995) and resistance parameters (R) and reactance (Xc), in Ohm, by impedanciometer RJL Systems Electrode Placement. Height/ age index and body mass/ age index were classified based on WHO (2007). Body composition was evaluated by Bioelectric Impedance Vector Analysis (BIVA) according to Piccoli et al (1994). Comparisons between anthropometry and BIVA classifications were done graphically, based on the tolerance ellipses of RXc graph. Significant p values <0.05. Results: The average age of the sample was 10.8 years (+2.9), 56.8% of adolescents and 50.6% of males. Prevalence of stunting (H/A) of 15.5% and 19.9% and overweight (BMI/ age) of 5.7% and 6.7% were found, respectively for children and adolescents. For both sexes and age groups deviation toward the lower left quadrant of RXC graph was shown, indicating a higher proportion of fat in relation to not fat tissues. For male children, proportion of subjects beyond the 95% tolerance ellipse was 2.7% and proportion of subjects with discrepant classifications, relative to anthropometry, was 94.6%. The same proportions achieved, respectively, 2.3% and 77.1% of male adolescents, 2.5% and 85.4% of female children, and 0.6% and 94.8% of female adolescents. Conclusions: The study points the nutritional transition among the Kaingang, characterized by important prevalence of stunting and overweight. Discrepancies between classifications of BMI/age and BIVA signal the necessity of studies that look for the conciliation of differents nutritional evaluation techniques, as anthropometry and BIA.

Introdução: a prevalência de obesidade infantil tem aumentado rapidamente no Brasil nas últimas décadas. Por isso, há uma necessidade urgente de desenvolver estratégias efetivas na prevenção e controle da obesidade infantil. Neste contexto, foi desenvolvido um programa de intervenção com educação nutricional e atividade física no âmbito escolar, com o objetivo de prevenção e controle da obesidade, denominado TriAtiva: educação, alimentação e atividade física. Métodos: trata-se de um estudo controlado randomizado por conglomerado, conduzido em 12 escolas municipais da cidade de Porto Alegre/RS (6 escolas intervenção e 6 escolas controle), do primeiro ao quarto ano do ensino fundamental, durante um ano letivo. O Programa TriAtiva foi implementado nas escolas de intervenção, através de práticas educativas relacionadas à alimentação saudável e à atividade física, visando ao desenvolvimento da saúde do aluno em um ambiente favorável, com o envolvimento da comunidade escolar e dos familiares. Foi considerado desfecho primário o índice de massa corporal e como desfechos secundários o percentual de gordura corporal, circunferência da cintura, além da prevalência, incidência e remissão do excesso de peso e obesidade. Resultados: foram avaliados 600 escolares, com uma perda de 10,3% até o final do estudo. Comparados ao grupo controle, escolares do grupo intervenção apresentaram redução no índice de massa corporal (IMC), com diferença de média padronizada (DMP) de -0,18 (IC95%: -0,27 a -0,08; P=0,002), no peso com DMP de -0,10 (IC95%: - 0,16 a -0,04; P=0,004) e no escore Z do IMC com DMP de -0,19 (IC95%: -0,29 a -0,09; P=0,002), todos com significância estatística. Também houve redução, mas não estatisticamente significativa, na circunferência da cintura com DMP de -0,07 (IC95%: -0,13 a 0,02; P=0,06) e no percentual de gordura corporal com DMP de -0,07 (IC95%: -0,28 a 0,14; P=0,47). O grupo intervenção apresentou mudança com a redução na prevalência de excesso de peso e obesidade com odds ratio (OR) de 0,77 (IC95%:0,61 a 0,97; P=0,02) e OR de 0,54 (IC95%: 0,44 a 0,67; P<0,001), respectivamente. Também houve aumento na remissão do excesso de peso e obesidade, com OR de 3,57 (IC95%: 1,39 a 9,09; P=0,008) e OR de 7,69 (IC95%: 3,94 a 14,28; P<0,001), respectivamente. Mas não houve mudanças na incidência do excesso de peso com OR de 0,57 (IC95%: 0,20 a 1,62; P= 0,29) e na obesidade com OR de 0,89 (IC95%: 0,18 a 4,28; P=0,88). Conclusão: o Programa TriAtiva apresentou efeitos positivos no IMC e mudanças favoráveis na prevalência e remissão da obesidade, após o término do programa, tornando-se um aliado na prevenção e controle da obesidade, no âmbito escolar. Registro Brasileiro de Ensaios Clínicos: RBR- 2xx2z4. / Introduction: The prevalence of childhood obesity has increased rapidly in Brazil in the last decades. Therefore, there is an urgent necessity to develop effective strategies for the prevention and control of childhood obesity. In this context, it was developed an intervention program with nutrition education and physical activity at schools, with objectives to prevent and control obesity, called TriAtiva: education, nutrition and physical activity. Methods: This is a cluster randomized controlled trial, conducted in 12 public schools in Porto Alegre/RS (6 intervention schools and 6 control schools), from first to fourth grade from elementary school during one school year. The TriAtiva Program was implemented in the intervention schools through educational practices associated to healthy eating and physical activity, aimed the development of the health for student in a favorable environment, with the involvement of the school community and family. The body mass index was considered the primary outcome and the secondary outcomes were the percentage of body fat, waist circumference, beyond the prevalence, incidence and remission of overweight and obesity. Results: 600 students were assessed, the loss was 10.3% until the end of the study. Compared to the control group, students in the intervention group showed a reduction in body mass index (BMI), the standardized mean difference (SMD) was -0.18 (95% CI: -0.27 to -0.08; P = 0.002 ), SMD for the weight was -0.10 (95% CI: - 0.16 to -0.04; P = 0.004) and for BMI z-score was -0.19 (95% CI: -0.29 to -0.09; P = 0.002), all with statistical significance. There was a reduction, but not statistically significant, in waist circumference, where SMD was -0.07 (95% CI: -0.13 to 0.02; P = 0.06) and SMD for percentage of body fat was -0.07 (95% CI: -0.28 to 0.14; P = 0.47). The intervention group showed a change with a reduction in the prevalence of overweight and obesity, odds ratio (OR) was 0.77 (95% CI: 0.61 to 0.97; P = 0.02) and 0.54 (95% CI: 0.44 to 0.67; P < 0.001), respectively. Also there was an increase in the remission of overweight and obesity, where OR was 3.57 (95% CI: 1.39 to 9.09; P = 0.008) and 7.69 (95% CI: 3.94 to 14.28; P < 0.001), respectively. Although there were no changes in the incidence of overweight where OR was 0.57 (95% CI: 0.20 to 1.62; P = 0.29) and for obesity OR was 0.89 (95% CI: 0.18 to 4.28; P = 0.88). Conclusion: TriAtiva program showed positive effects on BMI and favorable changes in the prevalence and remission of obesity, after the program ends, becoming an allied in the prevention and control of obesity at schools. Brazilian Clinical Trials Registry (ReBec): RBR- 2xx2z4.

Introdução: A doença de Machado-Joseph (DMJ) ou ataxia espinocerebelar tipo 3 (SCA3) é causada por uma expansão de trinucleotídeos CAG no gene ATXN3, que leva à degeneração de múltiplos sistemas neurológicos. Seu curso é invariavelmente progressivo, não havendo tratamento específico. Objetivos: Descrever novos biomarcadores, aspectos não motores e definir quais escalas clínicas devem ser utilizadas como desfechos principais nos futuros ensaios clínicos randomizados (ECR) para a DMJ/SCA3. Além de avaliar se o tratamento com carbonato de lítio é seguro e efetivo em reduzir a progressão desta condição. Métodos: Em estudo caso-controle avaliamos: 1) a relação dos sintomas depressivos na DMJ/SCA3, pelo inventário de Beck (BDI), com aspectos de gravidade clínica e molecular; 2) alterações no índice de massa corporal (IMC) e sua correlação com aspectos clínico-moleculares e de neuroimagem; e 3) o Sistema Insulina/ IGF-1 (IIS) e o potencial de seus componentes como biomarcadores. Fizemos uma revisão sistemática sobre os aspectos psicométricos das escalas clínicas de SCAs já descritas, para em seguida iniciarmos um ECR, duplo-cego, paralelo, placebo-controlado de fase 2/3. Para este estudo foram randomizados 62 pacientes com diagnóstico molecular prévio de DMJ/SCA3 com marcha independente e ≤ 10 anos de doença (1:1) para tratamento com carbonato de lítio (0.5-0.8mEq/L) ou placebo. Resultados: Os escores do BDI foram mais elevados na DMJ/SCA3 (p= 0.012) e correlacionaram-se significativamente apenas com as escalas SARA (R=0.359, p=0.01) e NESSCA (R=0.412, p=0.003). Os pacientes com DMJ/SCA3 (N=46) apresentaram IMC menor (24.4 ± 4.1) do que os indivíduos controle (N=42, 27.1± 4.5, p=0.01), havendo correlação inversa (R=−0.396, p=0.015) entre o IMC e o tamanho da sequencia repetitiva CAG (CAGn). Encontramos uma maior sensibilidade periférica à insulina (HOMA2-%S, p=0.003, corrigido pelo IMC) e níveis séricos mais elevados da proteína ligante do IGF-1, IGFBP-1 (p=0.001) na DMJ/SCA3. A IGFBP1 correlacionou-se diretamente à CAGn (R=0.452; p = 0.006) e a sensibilidade à insulina inversamente à idade de início dos sintomas (R=-0.444; P = 0.003). Concluímos, na revisão sistemática, que as escalas semi-quantitativas SARA e NESSCA, e as quantitativas SCAFI e CCFS seriam os melhores desfechos para um ECR. O uso de lítio foi seguro após 24 semanas de tratamento, não havendo diferenças no número total de eventos adversos entre os grupos lítio (50,3%) e placebo (49,7%, p=1.00). O grupo placebo apresentou maior progressão (que não foi significativa) nos escores NESSCA (0.35 pontos, 95% IC -1.0 a 1.7, p=0.222, desfecho primário de efetividade) e SARA (0.96 pontos, 95% IC -0.46 a 2.38, p=0.329), após 48 semanas de tratamento. A gravidade da ataxia de marcha (p=0.008), as provas funcionais quantitativas: PATA rate (p=0.002) e Click Test ND (p=0.023), e os escores compostos SCAFI (p=0.015) e CCFS (p=0.029) apresentaram menor progressão no grupo tratado com lítio durante as 48 semanas. Conclusão: Os resultados destes estudos ajudam no entendimento da depressão e alterações nutricionais da DMJ/SCA3 e apontam a IGFBP-1 como biomarcador e a sensibilidade periférica insulínica como modificador do fenótipo. Houve efetividade do tratamento com carbonato de lítio nos desfechos secundários do ECR, sendo necessária confirmação por ensaios clínicos multicêntricos. / Background: Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is caused by a CAG repeat expansion at ATXN3 gene, leading to progressive degeneration of multiple neurological systems. MJD/SCA3 is an invariably progressive disorder, with no current treatment. Objectives: To describe new disease biomarkers, non-motor aspects and to define the clinical SCA scales to be utilized as main outcomes in future randomized controlled trials (RCT) on MJD/SCA3. And further assess safety and effectiveness of lithium carbonate in reducing the progression of this condition. Methods: We performed a case-control study to evaluate: 1) the relation of MJD/SCA3 depressive symptoms, through Beck depression Inventory (BDI), with other clinical and molecular findings; 2) the Body Mass Index (BMI) of MJD/SCA3 patients and the correlation with other clinical, molecular and neuroimaging findings; and 3) the Insulin/IGF-1 system (IIS) in MJD/SCA3 and the possible biomarker properties of its components. We further performed a systematic review on the psychometric properties of the described SCAs scales in order to initiate the double-blind, parallel, placebo-controlled phase 2/3 clinical trial. 62 independently ambulatory MJD/SCA3 patients with ≤ 10 years of disease duration were randomly assigned in the RCT (1:1) to lithium (0.5-0.8mEq/L) or placebo. Results: BDI scores were higher in MJD/SCA3 patients (p= 0.012), with significant correlations only with the scales SARA (R=0.359, p=0.01) and NESSCA (R=0.412, p=0.003). MJD/SCA3 patients (N=46) presented lower BMI (24.4 ± 4.1) than control individuals (N=42, 27.1± 4.5, p=0.01). BMI correlated inversely with the length of the expanded CAG repeat (CAGn). We found higher peripheral sensitivity to insulin (HOMA2-%S, p=0.003, corrected for BMI) and serum levels of the IGF-1 binding protein, IGFBP-1 (p=0.001) in MJD/SCA3. IGFBP-1 correlated with CAGn (R=0.452; p = 0.006) and insulin sensitivity with the age of disease onset (R=-0.444; P = 0.003). In the systematic review we concluded that the semiquantitative SCA scales SARA and NESSCA and the quantitative instruments SCAFI and CCFS would be the most appropriate outcomes for the RCT. After 24 weeks, there were no differences in the number of adverse events in lithium (50.3%) and placebo (40.7%) groups (p=1.00) in the RCT. The placebo group presented a non-significant faster progression on NESSCA (0.35 points, 95% CI -1.0 to 1.7, p=0.612, primary effectiveness outcome) and SARA (0.96 points, 95% CI -0.46 to 2.38, p=0.186), after 48 weeks of treatment. Gait ataxia severity (p=0.008), the quantitative performance tasks: PATA rate (p=0.002) and Click Test ND (p=0.023), and the composite scores SCAFI (p=0.015) and CCFS (p=0.029) presented a slower progression under lithium therapy in the overall 48 weeks period. Conclusion: These studies added to the understanding of depressive and nutritional manifestations of MJD/SCA3 and points IGFBP-1 as a biomarker and peripheral insulin sensitivity as a disease phenotype modifier. The effectiveness of lithium carbonate treatment shown in secondary outcomes of the RCT opened a perspective for an effective therapy for this untreatable disorder that must be confirmed by large multicentric clinical trials.