アルツハイマー病に対する高用量donepezilの1年間の治療効果

Clinical Effects of a High Oral Dose of Donepezil in Patients with Alzheimer's Disease：A 1-year Follow-up Study

抄録

　高度アルツハイマー病の認知機能障害に対しdonepezil 10mgがわが国においても認可されたが，副作用の問題や長期間の治療効果に対する懸念もあり，使用を避けている場合も少なくない。今回，我々はdonepezil 5mgを服用していた軽度から高度のアルツハイマー病患者に対し，donepezil 10mgへ増量した際の効果と副作用について，アポリポ蛋白E遺伝子型との関連を含めて検討した。その結果，donepezil 10mgの内服により24週間以上の期間，認知機能障害の進行抑制が可能であると考えられた。52週後より次第に認知機能障害が進行することが示唆されたが，5mg内服継続より進行抑制に対し効果があると考えられた。また，認知機能障害の比較的軽度群のほうが高度群よりdonepezil 10mgの有効性が高いと考えられ，早期に適応が拡大される必要性が示唆された。アポリポ蛋白E遺伝子ε4の存在は，donepezil 10mgの治療効果に影響しないと考えられた。

　In Japan, administration of 10mg donepezil has been authorized for cognitive impairment in patients with severe Alzheimer's disease (AD)；however, because of the concerns regarding the side effects and long-term efficacy of this high donepezil dose (10mg), its usage is still limited. In other countries, 10mg donepezil is already confirmed to be effective for cognitive impairment in patients with mild to moderate AD. We have previously reported the effects of 10mg donepezil in a 6 month study：however, no study has analyzed the long-term, i.e., ＞6 months, data in Japanese patients. In this study, we investigated the efficacy and safety of 10mg donepezil in patients with mild to severe AD who had previously been administered 5mg donepezil. Further, the relationship between the effects of 10mg donepezil and the apolipoprotein E4 genotype was also examined. The results, showed that 10mg donepezil inhibited the progress of cognitive impairment in mild to severe AD patients for more than 24 weeks. Although cognitive impairment progressed at 52 weeks after administration, a 10mg donepezil dose was considered to be more effective than a 5mg donepezil. In addition, this high dose was more effective in mild to moderate AD patients than in severe AD patients. Thus, the use of 10mg donepezil in milder AD patients was considered to be benifical. The apolipoprotein E4 genotype did not have any impact on the effects of 10mg donepezil.