Hampstead Benjamin M, Sathian Krishnankutty, Bikson Marom, Stringer Anthony Y
Mental Health Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.
Neuropsychology Program, Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
Alzheimers Dement (N Y). 2017 May 15;3(3):459-470. doi: 10.1016/j.trci.2017.04.008. eCollection 2017 Sep.
Memory deficits characterize Alzheimer's dementia and the clinical precursor stage known as mild cognitive impairment. Nonpharmacologic interventions hold promise for enhancing functioning in these patients, potentially delaying functional impairment that denotes transition to dementia. Previous findings revealed that mnemonic strategy training (MST) enhances long-term retention of trained stimuli and is accompanied by increased blood oxygen level-dependent signal in the lateral frontal and parietal cortices as well as in the hippocampus. The present study was designed to enhance MST generalization, and the range of patients who benefit, via concurrent delivery of transcranial direct current stimulation (tDCS).
This protocol describes a prospective, randomized controlled, four-arm, double-blind study targeting memory deficits in those with mild cognitive impairment. Once randomized, participants complete five consecutive daily sessions in which they receive either active or sham high definition tDCS over the left lateral prefrontal cortex, a region known to be important for successful memory encoding and that has been engaged by MST. High definition tDCS (active or sham) will be combined with either MST or autobiographical memory recall (comparable to reminiscence therapy). Participants undergo memory testing using ecologically relevant measures and functional magnetic resonance imaging before and after these treatment sessions as well as at a 3-month follow-up. Primary outcome measures include face-name and object-location association tasks. Secondary outcome measures include self-report of memory abilities as well as a spatial navigation task (near transfer) and prose memory (medication instructions; far transfer). Changes in functional magnetic resonance imaging will be evaluated during both task performance and the resting-state using activation and connectivity analyses.
The results will provide important information about the efficacy of cognitive and neuromodulatory techniques as well as the synergistic interaction between these promising approaches. Exploratory results will examine patient characteristics that affect treatment efficacy, thereby identifying those most appropriate for intervention.
记忆缺陷是阿尔茨海默病性痴呆以及被称为轻度认知障碍的临床前驱阶段的特征。非药物干预有望改善这些患者的功能,有可能延缓标志着向痴呆转变的功能损害。先前的研究结果表明,记忆策略训练(MST)可增强对训练刺激的长期记忆,并伴有外侧额叶和顶叶皮质以及海马体中血氧水平依赖信号的增加。本研究旨在通过同时给予经颅直流电刺激(tDCS)来增强MST的泛化能力以及受益患者的范围。
本方案描述了一项针对轻度认知障碍患者记忆缺陷的前瞻性、随机对照、四臂、双盲研究。一旦随机分组,参与者连续完成五个每日疗程,期间他们在左侧前额叶皮质接受有源或伪高清tDCS,该区域已知对成功的记忆编码很重要,并且已被MST激活。高清tDCS(有源或伪)将与MST或自传体记忆回忆(类似于回忆疗法)相结合。参与者在这些治疗疗程前后以及3个月随访时使用生态相关测量和功能磁共振成像进行记忆测试。主要结局指标包括面孔-名字和物体-位置关联任务。次要结局指标包括记忆能力的自我报告以及空间导航任务(近迁移)和散文记忆(用药说明;远迁移)。将在任务执行和静息状态期间使用激活和连通性分析来评估功能磁共振成像的变化。
结果将提供有关认知和神经调节技术疗效以及这些有前景的方法之间协同相互作用的重要信息。探索性结果将检查影响治疗疗效的患者特征,从而确定最适合干预的患者。