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A History of Antidementic Drug Development in Japan

Masatoshi Takeda, Shinji Tagami

Objective: Japan is the top runner in the world in society aging, in which the number of patients with Alzheimer’s disease has significantly increased and still keeps increasing. Many countries and societies are still struggling with people with dementia and the burden related to the high number of the elderly. In this study, both authors have been involved with research works on elucidating the pathological process of Alzheimer’s disease and developing antidementic drugs for more than 30 years. Methods: Based on lifetime professional experiences in basic research and clinical work as well as our own contribution in the areas of expertise, we describe in this review the changes of the number of dementia patients and the concept of dementia, as well as the development of antidementic drugs in Japan. Results: In this review, we define the super-aged society first. Historical concept changes in Alzheimer’s disease, perspectives of research on Alzheimer’s disease and drug development, history of antidementic drug developments (for nootropics and drugs for improving brain metabolism and circulation, development of symptom-modifying drugs; hormones, neurotrophic factors, etc.; acetylcholinergic drugs; and glutamatergic drugs), and development of disease-modifying drugs (with amyloid cascade hypothesis, nonsteroidal anti-inflammatory drugs, and amyloid vaccine) have been outlined as review sections. Finally, we devote discussion in two review sections – failure of new drugs and development from the existing drugs as well as development of preemptive medicine. Conclusion: We hope that the whole society, including the elderly with and without cognitive decline, can resolve this issue in the near future.
Key Word Alzheimer’s disease, acetylcholine esterase inhibitor, γ-secretase inhibitor, immunotherapy
Editorial Committe, Taiwanese Journal of Psychiatry
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