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在阿尔茨海默病前驱期的一项随机多奈哌齐试验中,基底前脑萎缩进展减少。

Reduced basal forebrain atrophy progression in a randomized Donepezil trial in prodromal Alzheimer's disease.

机构信息

AXA Research Fund & UPMC Chair, Paris, France; Sorbonne Universities, Pierre et Marie Curie University, Paris 06, Institute of Memory and Alzheimer's Disease (IM2A) & Brain and Spine Institute (ICM) UMR S 1127, Department of Neurology, Hopital Pitié-Salpêtrière, Paris, France.

Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.

出版信息

Sci Rep. 2017 Sep 15;7(1):11706. doi: 10.1038/s41598-017-09780-3.

Abstract

Acetylcholinesterase inhibitors are approved drugs currently used for the treatment of Alzheimer's disease (AD) dementia. Basal forebrain cholinergic system (BFCS) atrophy is reported to precede both entorhinal cortex atrophy and memory impairment in AD, challenging the traditional model of the temporal sequence of topographical pathology associated with AD. We studied the effect of one-year Donepezil treatment on the rate of BFCS atrophy in prodromal AD patients using a double-blind, randomized, placebo-controlled trial of Donepezil (10 mg/day). Reduced annual BFCS rates of atrophy were found in the Donepezil group compared to the Placebo treated arm. Secondary analyses on BFCS subregions demonstrated the largest treatment effects in the Nucleus Basalis of Meynert (NbM) and the medial septum/diagonal band (Ch1/2). Donepezil administered at a prodromal stage of AD seems to substantially reduce the rate of atrophy of the BFCS nuclei with highest concentration of cholinergic neurons projecting to the cortex (NbM), hippocampus and entorhinal cortex (Ch1/2).

摘要

乙酰胆碱酯酶抑制剂是目前批准用于治疗阿尔茨海默病(AD)痴呆的药物。据报道,基底前脑胆碱能系统(BFCS)萎缩先于 AD 患者的内嗅皮质萎缩和记忆障碍,这对与 AD 相关的拓扑病理学时间顺序的传统模型提出了挑战。我们使用双盲、随机、安慰剂对照的多奈哌齐(10mg/天)试验研究了一年多奈哌齐治疗对前驱 AD 患者 BFCS 萎缩速度的影响。与安慰剂治疗组相比,多奈哌齐组的 BFCS 每年萎缩率降低。对 BFCS 亚区的二次分析表明,核基底神经节(NbM)和中隔/斜角带(Ch1/2)的治疗效果最大。在 AD 的前驱阶段给予多奈哌齐治疗,似乎可显著降低投射到皮质(NbM)、海马和内嗅皮质(Ch1/2)的胆碱能神经元浓度最高的 BFCS 核的萎缩速度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd47/5601919/092fd5eb3dea/41598_2017_9780_Fig1_HTML.jpg

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