Kirsten de Oude

Chapter 1: General introduction Although cardiovascular disease (CVD) is the leading cause of death worldwide, the risk of CVD can be reduced by addressing modifiable risk factors such as physical inactivity, poor diet, and obesity. Regular physical activity is essential for reducing cardiovascular risk factors (CVRFs). Adults with intellectual disabilities (ID) are particularly vulnerable for CVD, experiencing higher rates of CVRFs compared to the general population. This group faces unique challenges in maintaining a healthy lifestyle, accessing healthcare, and receiving appropriate prevention and screening programmes. These difficulties result in persistent health inequalities. In the Netherlands, cardiovascular risk management for adults with ID generally follows guidelines developed for the general population. However, these guidelines require individualised adjustments due to comorbidities, polypharmacy, and communication barriers. Increasing physical activity levels is one of the recommendations in international guidelines. However, physical activity levels among adults with ID are often low, and they encounter numerous barriers to participate in physical activity, including health problems, lack of adapted programmes, and insufficient support. Resistance training may offer unique benefits for adults with ID, such as improvements in muscle mass, glycaemic control, blood pressure, and lipid profiles, and is more easily tailored to individual abilities than aerobic training. Despite these potential benefits, adults with ID remain underrepresented in clinical research, resulting in a lack of evidence about the effects of resistance training on health-related factors, such as CVRFs, physical fitness, body composition, sarcopenia, activities of daily living (ADL), falls, and challenging behaviour. This thesis aims to investigate the effects of Progressive Resistance Exercise Training (PRET) on CVRFs and other health outcomes in adults with ID, addressing a significant knowledge gap and providing evidence to inform clinical practice and policy. Chapter 2: Effect of different training intensities on CVRFs This chapter presents a systematic literature review and meta-analyses on the effects of different resistance training intensities (low, moderate, high, progressive) on CVRFs in the general population. While resistance training is known to improve CVRFs, the optimal training intensity remains unclear. Across 59 randomised controlled trials, progressive resistance training intensity showed beneficial effects on systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL). High intensity resistance training reduced glycated haemoglobin (HbA1c), low intensity training lowered LDL, and moderate intensity resistance training improved both waist-hip ratio (WHR) and HbA1c. Comparisons between intensities revealed no statistically significant differences, apart from a stronger effect of high intensity on WHR. The certainty of evidence ranged from low to moderate. Overall, these findings confirm that resistance training at various intensities contribute to improvements in CVRFs. However, evidence for the optimal training intensity remains limited, highlighting the need for further studies to determine optimal training prescriptions for cardiovascular risk management. Chapter 3: PRET study protocol: Design and methodolody This chapter describes the protocol for the PRET study, that aimed to evaluate the effect of progressive resistance exercise training on CVRFs in adults with ID. While resistance training has proven to be effective on reducing CVRF’s in the general population, its effect in adults with ID remains unknown. We designed a repeated time-series study with one study group. Adults with mild-to-moderate ID and at least two CVRFs were eligible for inclusion. Following a 12-week baseline period with repeated measurements, participants completed the 24-week PRET intervention, after which all outcomes were reassessed. After a12 weeks follow-up period, participants had their final assessments. Hierarchical regression models, adjusted for possible confounders, were used to evaluate intervention and follow-up effects. The results of the PRET study are presented in chapters 5 and 6. Primary outcomes (chapter 5) included HbA1c, SBP, LDL, and WHR. Secondary outcomes (chapter 6) covered physical fitness, body composition, sarcopenia, ADL, falls, and challenging behaviour. Chapter 4: Measuring muscle mass in adults with ID This chapter reports on the construct validity and intra-rater reliability of calf circumference as a proxy measurement for muscle mass in adults with ID. Compared to bioelectrical impedance analysis (BIA), calf circumference is a less expensive and a more accessible method for adults with ID. We analysed data from 36 participants in the PRET study. Pearson’s correlations revealed a weak association between calf circumference and skeletal muscle mass (SMM), and moderate correlations with segmental muscle mass (SegMM) and skeletal muscle index (SMI). Intra-rater reliability of calf circumference was excellent. Although calf circumference measurements are highly reliable within assessors, their validity in estimating muscle mass compared to BIA is limited. Calf circumference may serve as a rough indicator of muscle mass when other methods are unavailable. Due to the strict inclusion criteria for CVRFs in the PRET study, findings are not generalisable to all adults with ID. Future research should include a more heterogeneous sample and use Dual-energy X-ray Absorptiometry (DXA) or Computed Tomography (CT) scans for validation. Chapter 5: Effect of PRET on CVRFs This chapter presents the results for the primary outcomes of the PRET study introduced in chapter 3. Thirty-six adults with ID participated in the study. We used multilevel linear regression models, adjusted for medication use, to investigate the effects of the PRET intervention. While improvements were observed across HbA1c, SBP, LDL, and WHR only LDL showed a statistically significant improvement. After the follow-up period, levels for HbA1c, SBP, and LDL worsened, while WHR showed a slight improvement. The flexibility of the PRET intervention allowed trainers to adapt exercises to participant capabilities, improving real-world applicability. However, adherence was still a major challenge, as we observed a 28% drop-out rate despite the use of motivational strategies and individualised support. The findings of this study suggest that PRET is a promising intervention for managing CVRFs in adults with ID, particularly for those who are motivated and capable of adhering to structured exercise programs. Further research is needed to improve adherence and to evaluate the effectiveness in a larger sample of adults with ID. Chapter 6: Effect of PRET on secondary health outcomes This chapter describes the effects of the PRET intervention on secondary outcomes, including body composition, physical fitness, sarcopenia, ADL, challenging behaviour, and falls, in adults with ID. Statistically significant improvements were observed in lower body functional muscle strength and endurance and several domains of challenging behaviour (irritability, lethargy, hyperactivity, inappropriate speech). However, no changes were found in body composition, other domains of physical fitness, ADL, or falls. We aimed to investigate the effect of PRET on the presence of sarcopenia. However, no cases of sarcopenia were identified at baseline, and analysis was not possible. Given the small sample size, and the fact that participants were not specifically recruited based on the presence of the measured secondary outcomes, these findings suggest that PRET has the potential to be a valuable intervention with positive effects across multiple health components in adults with ID. Chapter 7: General discussion This thesis shows that PRET can improve CVRFs in adults with ID, with significant reductions in LDL cholesterol and improvements in lower body performance and challenging behaviour. However, changes in body composition were minimal, and no significant effects were observed for other physical fitness measures, ADL, or falls. Adherence remained a challenge, with a 28% dropout rate, despite strategies to enhance motivation and accessibility. Methodological limitations included a small, selected sample, restricting statistical power and generalisability. The lack of change in body composition may be attributed to the relatively short intervention duration, the modest training frequency of twice a week, the absence of dietary modifications, and potentially high levels of sedentary behaviour outside the intervention. Proxy reporting of physical activity also limited data reliability. Future research should include larger, more diverse samples, objective measurements of physical activity and sedentary behaviour and consider multicomponent interventions combining exercise with nutritional support. For practice, the PRET intervention offers a feasible tool for resistance training in adults with ID, but optimal outcomes require a multidisciplinary approach involving caregivers, family, and other healthcare professionals to increase adherence and motivation. Policymakers should support development in motivational and adaptive skills for healthcare professionals to address the diverse needs of this population. Overall, PRET can improve cardiovascular health in adults with ID, but sustained adherence and a multicomponent and multidisciplinary approach is essential for maximising benefits.