A novel therapeutic strategy for vascular dementia: dual energy supply with glucose and ketone body

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K15364
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Kitamura Akihiro 滋賀医科大学, 医学部, 助教 (80636019)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 血管性認知症 / ケトン体 / 1, 3-ブタンジオール

Outline of Final Research Achievements

To assess the utility of 1,3-butanediol (BD) in vascular dementia, where chronic cerebral hypoperfusion is the major cause, we created a mouse model of vascular dementia by surgically implanting microcoils on both common carotid arteries. We compared four groups: normal diet, normal diet + 1,3-BD, ketogenic diet, and sham surgery + normal diet. On the 28th day post-surgery, we conducted comparative investigations including body weight, blood glucose and ketone measurement, spatial working memory, cerebral blood flow, and histological analysis. Under normal dietary conditions, 1,3-BD significantly increased ketone levels and demonstrated significant improvement in spatial working memory in the model of chronic cerebral hypoperfusion. These findings suggest the potential of this compound as a novel therapeutic agent for vascular dementia.

Free Research Field

血管性認知症

Academic Significance and Societal Importance of the Research Achievements

生活習慣病である脳卒中は我が国の死因の第4位，寝たきりの第1位の原因であり，全医療費の実に1割近くが脳卒中診療に費やされ，なかでも血管性認知症は、患者の日常動作制限や生活の質の低下によりその介護者にまで多大な負担を及ぼす。種々の新しい病態と治療が研究されているなか、依然として根本的な治療法がなく、開発が急務であり、創薬ニーズが極めて高い。
1,3-BDは通常食事下でケトン体濃度を有意に増加させ、慢性脳低灌流モデルマウスにおいて空間作業記憶の有意な改善を示した。同薬剤が血管性認知症の新たな治療薬となる可能性が示唆された。今後、臨床応用に向けての取り組みが必要となる。