Cholinergic enhancement of functional networks in older adults with mild cognitive impairment.
Cholinergic enhancement of functional networks in older adults with mild cognitive impairment.
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DOI：
10.1002/ana.23874
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发表时间：
2013-06
影响因子：
11.2
通讯作者：
Gazzaley, Adam
中科院分区：
文献类型：
--
作者：
Pa, Judy;Berry, Anne S.;Compagnone, Mariana;Boccanfuso, Jacqueline;Greenhouse, Ian;Rubens, Michael T.;Johnson, Julene K.;Gazzaley, Adam
胆碱能系统对认知功能的重要性在动物和人类研究中得到了充分的证明。本研究的目的是阐明与乙酰胆碱（ACh）水平升高相关的认知和功能连接变化。我们假设，与安慰剂对照组相比，乙酰胆碱酯酶抑制剂（多奈哌齐）治疗轻度记忆障碍的老年人会表现出行为和功能网络的增强。我们进行了一项为期3个月，双盲，安慰剂对照研究的影响多奈哌齐在27名老年人轻度记忆缺陷。参与者完成了延迟识别记忆任务。在治疗前的基线和3个月随访时收集功能磁共振成像扫描，同时接受10 mg每日剂量的多奈哌齐或安慰剂。与安慰剂组相比，多奈哌齐治疗显著增强了面部和场景记忆探针的反应时间。确定了左侧梭状面区（FFA）与海马和下额交界处的功能网络连接的组间访视相互作用，因此与安慰剂组相比，治疗组显示出随时间推移的连接性增加。此外，FFA和海马功能网络连接的增强显著预测了治疗组3个月随访时的记忆反应时间。这些发现表明，增加胆碱能传递改善目标导向的神经处理和认知能力，并可能有助于促进跨功能连接的注意力和记忆网络的通信。纵向功能磁共振成像是一个有用的方法，阐明与药物调制的神经变化，是一个潜在的工具，监测干预疗效的临床试验。
The importance of the cholinergic system for cognitive function has been well-documented in animal and human studies. The objective of this study was to elucidate the cognitive and functional connectivity changes associated with enhanced acetylcholine (ACh) levels. We hypothesized older adults with mild memory deficits would show behavioral and functional network enhancements with an acetylcholinesterase inhibitor treatment (donepezil) when compared to a placebo control group. We conducted a 3-month, double-blind, placebo-controlled study on the effects of donepezil in twenty-seven older adults with mild memory deficits. Participants completed a delayed recognition memory task. FMRI scans were collected at baseline prior to treatment and at 3-month follow-up while on a 10 mg daily dose of donepezil or placebo. Donepezil treatment significantly enhanced the response time for face and scene memory probes when compared to the placebo group. A group-by-visit interaction was identified for the functional network connectivity of the left fusiform face area (FFA) with the hippocampus and inferior frontal junction, such that the treatment group showed increased connectivity over time when compared to the placebo group. Additionally, the enhanced functional network connectivity of the FFA and hippocampus significantly predicted memory response time at 3-month follow-up in the treatment group. These findings suggest that increased cholinergic transmission improves goal-directed neural processing and cognitive ability and may serve to facilitate communication across functionally-connected attention and memory networks. Longitudinal fMRI is a useful method for elucidating the neural changes associated with pharmacological modulation and is a potential tool for monitoring intervention efficacy in clinical trials.
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影响因子：
25
作者：
Croxson PL;Kyriazis DA;Baxter MG
通讯作者：
Baxter MG
影响因子：
5.3
作者：
Chuah, Lisa Y. M.;Chee, Michael W. L.
通讯作者：
Chee, Michael W. L.
影响因子：
14.5
作者：
Bentley, P.;Driver, J.;Dolan, R. J.
通讯作者：
Dolan, R. J.
影响因子：
3.2
作者：
Buckner, RL;Snyder, AZ;Morris, JC
通讯作者：
Morris, JC
影响因子：
16.2
作者：
Bakker A;Krauss GL;Albert MS;Speck CL;Jones LR;Stark CE;Yassa MA;Bassett SS;Shelton AL;Gallagher M
通讯作者：
Gallagher M