As the prevalence of dementia and Alzheimer's disease (AD) increases worldwide, it is imperative to reflect on the major clinical trials in the prevention of dementia and the challenges that surround them. The pharmaceutical industry has focused on developing drugs that primarily affect the Aβ cascade and tau proteinopathy, while academics have focused on repurposed therapeutics and multi-domain interventions for prevention studies. This paper highlights significant primary, secondary, and tertiary prevention trials for dementia and AD, overall design, methods, and systematic issues to better understand the current landscape of prevention trials. We included 32 pharmacologic intervention trials and 9 multi-domain trials. Fourteen could be considered primary prevention, and 18 secondary or tertiary prevention trials. Major categories were Aβ vaccines, Aβ antibodies, tau antibodies, anti-inflammatories, sex hormones, and Ginkgo biloba extract. The 9 multi-domain studies mainly focused on lifestyle modifications such as blood pressure management, socialization, and physical activity. The lack of validated drug targets, and the complexity of the diagnostic frameworks, eligibility criteria, and outcome measurements for trials, make it difficult to show efficacy for both pharmacological and multi-domain interventions. We hope that this summative analysis of trials will stimulate discussion for scientists and clinicians interested in reviewing and developing preventative interventions for AD.
Keywords: Alzheimer's; Amyloid; Clinical trials; Cognitive impairment; Dementia; Methods; Outcomes; Prevention; Tau; Therapeutics.
© 2022. The American Society for Experimental NeuroTherapeutics, Inc.