Journey towards achieving preemptive medicine for dementia through imaging

Abstract

In neurodegenerative dementias exemplified by Alzheimer disease, various abnormal proteins such as amyloid β and tau accumulate in the brain, which are pathognomonic characteristic. These abnormal protein accumulations in the brain are considered important treatment targets for preemptive medicine for dementia, as they are observed prior to clinical symptoms such as memory loss and are closely associated with neuronal damage. In the United States, monoclonal antibodies against amyloid β in Alzheimer disease have already been approved as disease–modifying drugs for Alzheimer's patients. However, the interpretation of clinical trial data for approved drugs, medical–economic issues, and the effectiveness of such disease–modifying drugs as preemptive medicine for preclinical patients are still under discussion and require further evidence accumulation. Nevertheless, the emergence of the second and third candidate drugs for disease–modifying agents indicates that the future of preemptive medicine for dementia is not far away. In recent years, the development of disease–modifying drugs that lead the way for preemptive medicine for dementia has accelerated, partly due to the fact that brain imaging, such as amyloid PET, has become a fundamental technology in pathophysiology research and drug development processes. Among the aforementioned disease–modifying candidate drugs, some have achieved excellent study designs and cleverly achieved primary endpoints by utilizing tau PET in addition to amyloid PET. Thus, abnormal protein accumulations in the brain are important targets not only for treatment but also for diagnosis and assessment of treatment efficacy, and the development of imaging biomarker technology to visualize them has become a powerful promoter of the drug development process. This paper focuses on neuroimaging in relation to the recent progress in dementia pathophysiology research, and introduces examples of the role of disease–modifying drug development in achieving preemptive medicine for dementia. Additionally, the requirements for achieving preemptive medicine in actual clinical practice, as well as the use of imaging biomarkers and challenges in preemptive care practice are discussed.