A meta‐analysis and systematic review of interventions to prevent or treat cognitive decline related to Alzheimer's disease in adults with Down syndrome

Abstract

Down syndrome (DS) is a leading genetic risk factor for Alzheimer's disease (AD). Although prevention and treatment of AD are well documented for those without DS, less is known about individuals with DS. This review evaluates the efficacy of AD and dementia interventions in people with DS. It includes 26 articles with 1417 participants ages 18-69 in the qualitative synthesis and 17 articles with 1118 participants in the meta-analysis. Four types of interventions demonstrated small-to-moderate effects: pharmacological (n = 19), exercise (n = 5), environmental (n = 1), and cognitive training (n = 1). Significant treatment effects were observed across interventions (t(66) = 4.67, p < 0.0001, d = 0.29, 95% confidence interval [CI]: 0.16-0.40); however, high heterogeneity (I2 = 93.8% CI = 92.8-94.7) was noted, which was not explained by intervention type or outcome. The meta-analysis indicates that interventions enhance AD-related cognitive and behavioral outcomes, emphasizing the need for further research to address heterogeneity. This review was registered with PROSPERO: CRD42024567026. HIGHLIGHTS: This study is the first to comprehensively review both pharmacological and non-pharmacological interventions for Alzheimer's disease (AD) in individuals with Down syndrome (DS), extending previous reviews by including a meta-analysis and examining key mediating variables. Donepezil, the most studied pharmacological treatment, showed significant cognitive and behavioral improvements in individuals with DS, especially with longer treatment periods. However, further trials are needed to explore its efficacy in combination with non-pharmacological interventions. All seven non-pharmacological studies reported significant improvement, suggesting that even small doses of exercise and cognitive training can be effective and feasible for individuals with DS. Online formats may enhance scalability and reduce barriers to participation. Significant heterogeneity in cognitive assessments across studies highlights the need for standardized, sensitive assessments to enable meaningful comparisons of intervention effects. Additional studies are required to determine the long-term efficacy of pharmacological interventions like Donepezil and to assess the sustained impact of non-pharmacological interventions on key AD-related cognitive domains such as memory, language, and executive function.