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阿尔茨海默病的冷漠治疗:ASCOMALVA试验的中期结果。

Apathy Treatment in Alzheimer's Disease: Interim Results of the ASCOMALVA Trial.

作者信息

Rea Raffaele, Carotenuto Anna, Traini Enea, Fasanaro Angiola Maria, Manzo Valentino, Amenta Francesco

机构信息

Centre for Clinical Research, Telemedicine and Telepharmacy, University of Camerino, Camerino, Italy.

Neurology Unit, National Hospital, "A. Cardarelli", Naples, Italy.

出版信息

J Alzheimers Dis. 2015;48(2):377-83. doi: 10.3233/JAD-141983.

Abstract

BACKGROUND

Apathy is a common symptom in Alzheimer's disease (AD), but no treatment has proven to be effective, although administration of cholinesterase inhibitors has been associated with moderate improvements in the short term.

OBJECTIVE

This study has compared apathy scores of patients included in "ASCOMALVA" trial treated for two years with donepezil plus a cholinergic precursor (choline alphoscerate), to those of patients receiving donepezil alone with the purpose of assessing if the availability of a higher amount of acetylcholine by combining precursor loading and inhibition of neurotransmitter breakdown would counter apathy in AD.

METHODS

Apathy was measured at baseline and 3, 6, 9, 12, 18, and 24 months using the apathy subtest of the Neuropsychiatric Inventory in 113 mild-moderate AD patients. Two matched groups were compared: group 1 (56 subjects) treated with donepezil plus choline alphoscerate and group 2 (57 subjects) treated with donepezil alone. Frontal functions were explored by the Frontal Assessment Battery (FAB) at baseline.

RESULTS

Group 1 subjects showed, as a whole, a lower apathy score after 12 to 24 months. The caregiver distress was descreased after 6 to 24 months. Results were unrelated with cognitive scores measured by the MMSE and ADAS-cog test. Subjects with FAB in the normal range had significantly lower scores.

CONCLUSIONS

The combination of donepezil with choline alphoscerate is more effective than donepezil alone in countering symptoms of apathy in AD. This suggests that the availability in brain of a higher amount of acetylcholine could affect apathy in AD subjects with spared executive functions.

摘要

背景

冷漠是阿尔茨海默病(AD)的常见症状,但尚无治疗方法被证明有效,尽管使用胆碱酯酶抑制剂在短期内有适度改善。

目的

本研究比较了在“ASCOMALVA”试验中接受多奈哌齐加胆碱能前体(阿法骨化醇胆碱)治疗两年的患者与仅接受多奈哌齐治疗的患者的冷漠评分,目的是评估通过联合前体负荷和抑制神经递质分解来增加乙酰胆碱的可用性是否能对抗AD中的冷漠。

方法

使用神经精神科问卷的冷漠子测试,在基线以及3、6、9、12、18和24个月时对113例轻度至中度AD患者的冷漠情况进行测量。比较了两个匹配组:第1组(56名受试者)接受多奈哌齐加阿法骨化醇胆碱治疗,第2组(57名受试者)仅接受多奈哌齐治疗。在基线时通过额叶评估量表(FAB)探索额叶功能。

结果

总体而言,第1组受试者在12至24个月后冷漠评分较低。照顾者的痛苦在6至24个月后有所减轻。结果与通过简易精神状态检查表(MMSE)和阿尔茨海默病评估量表认知部分(ADAS-cog)测试测得的认知评分无关。FAB在正常范围内的受试者得分明显较低。

结论

多奈哌齐与阿法骨化醇胆碱联合使用在对抗AD中的冷漠症状方面比单独使用多奈哌齐更有效。这表明大脑中较高水平的乙酰胆碱可用性可能会影响执行功能未受损的AD患者的冷漠症状。

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