Enhancing Working Memory in Patients With Early Alzheimer's Disease Through the Enhancement of Dorsolateral Prefrontal Cortex Neuroplasticity: A TMS-EEG Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Change in N-back Task Performance
研究概览
简要总结
In this study the investigators aim at assessing and then enhancing neuroplasticity in the dorsolateral prefrontal cortex (DLPFC) and working memory - a key function of DLPFC - in patients with mild Alzheimer's disease (AD). The investigators will use Paired Associative Stimulation (PAS) paradigm to measure neuroplasticity and then a 4-week course of high-frequency repetitive Transcranial Magnetic Stimulation (rTMS) to the DLPFC to enhance cognitive function. Clinical and cognitive assessments will be done at baseline, one week, one month and 6 months after the rTMS course. Healthy controls will also be enrolled to carry out baseline cognitive assessments and a baseline measurement of neuroplasticity.
详细描述
Specific aim 1: To assess working memory in participants with Alzheimer's disease (AD) and its change in response to a 4-week course of bilateral rTMS of DLPFC.
Hypothesis 1a: Compared to healthy individuals, participants with AD will be impaired on the N-back task.
Hypothesis 1b: Compared to sham rTMS, active rTMS will result in improvement on the N-back task in participants with AD at 1 week and 4 weeks after the treatment.
Specific aim 2: To assess DLPFC theta-gamma coupling during working memory performance in AD and its change in response to a 4-week course of bilateral rTMS of DLPFC.
Hypothesis 2a: Compared to healthy individuals, participants with AD will be impaired on DLPFC theta-gamma coupling during the N-back task.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Active placebo coil will be used as a Sham condition. This coil effectively mimics the real stimulation producing somatic sensation and sound (contraction of scalp muscles) with minimal direct brain effects. Same stimulation parameters and site as active condition will be used.
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for AD participants:
- •Age 55 years or above.
- •Ability to understand and speak English.
- •Confirmed Diagnosis of Probable AD by NIA-AA criteria.
- •Either not taking Cognitive enhancers or taking them at a stable dose for the last 3 months.
- •Willingness and ability to provide informed consent or an ability to assent and availability of a substitute decision maker willing to provide consent on participant's behalf.
- •Corrected visual acuity enough to read newspaper headlines.
- •Ability to hear a raised conversational voice, with hearing aids if needed.
- •Inclusion criteria for healthy control participants:
- •Age 55 or above.
- •Willingness and ability to speak English.
- •Willingness and ability to provide informed consent.
- •Corrected visual acuity enough to read newspaper headlines.
- •Ability to hear a raised conversational voice, with hearing aids if needed.
排除标准
- •for AD participants:
- •MOCA score <
- •DSM IV - TR diagnosis of a current episode of mood disorder in the last 3 months.
- •DSM IV - TR diagnosis of a current anxiety disorder in the last 3 months.
- •DSM IV - TR diagnosis of a current substance use disorder in the last 3 months.
- •DSM IV - TR diagnosis of a current or lifetime primary psychotic disorder.
- •Diagnosis of intellectual disability or a neurodevelopmental disorder.
- •Electroconvulsive Therapy treatment in the last 6 months.
- •History of a seizure other than a febrile seizure in infancy.
- •Currently taking Anticonvulsants or Benzodiazepines.
- •Any contraindication for TMS or any other medical condition/circumstances that would make the study participation difficult for the participant.
- •Exclusion criteria for healthy control participants:
- •Meets criteria for a DSM IV - TR diagnosis other than simple phobias or Adjustment disorder.
- •Any other neurological disorder affecting central nervous system.
- •Psychotropic medication except for sedative /hypnotics at a stable dose for at least 4 weeks.
- •History of seizure other than a febrile seizure in infancy
- •Currently taking Anticonvulsants or Benzodiazepines.
- •Any contraindication for TMS or any other medical condition/circumstances that would make the study participation difficult for the participant.
研究组 & 干预措施
Alzheimer's disease rTMS
The intervention procedure done in this group is repetitive Transcranial Magnetic Stimulation.
干预措施: Repetitive Transcranial Magnetic Stimulation (Procedure)
Alzheimer's disease rTMS Sham
The intervention procedure done in this group is Repetitive Transcranial Magnetic Stimulation - Sham
干预措施: Repetitive Transcranial Magnetic Stimulation - Sham (Procedure)
Healthy Control
Healthy control group will only participate in baseline assessments which include baseline neuropsychological testing and baseline measurement of neuroplasticity. This will be used to standardize neuropsychological test scores and to compare the baseline neuroplasticity between healthy participants and Alzheimer's disease (AD) participants. Healthy control group will not get rTMS intervention.
结局指标
主要结局
Change in N-back Task Performance
时间窗: pre-intervention (baseline) and then 7 days, 4 weeks and 6 months after intervention
The N-Back is a working memory task where the subject is presented with a sequence of stimuli (letters). The task consists of indicating when the current stimulus matches the one from N steps earlier in the sequence. By measuring the accuracy on the N-back task, the investigators will assess the working memory at baseline and compare the change at 7days, 4 weeks and 6 months post-intervention. The investigators' pilot data suggests that this test is most discriminatory between AD participants and healthy controls. The N-back task will be administered while recording EEG online to assess theta-gamma coupling.
次要结局
- Changes in Cognitive Function Measures Scores(Change from baseline at 7 days, 4 weeks and 6 months after intervention.)
- Validating a new scale for insight in Alzheimer's disease.(Change from baseline at 7 days and 6 months after intervention.)
- Changes in Theta Phase-Gamma Amplitude Coupling(Change from baseline at 7 days, 4 weeks and 6 months after intervention.)
- Changes in DLPFC Neuroplasticity(Change from baseline at 7 days, 4 weeks and 6 months after intervention.)
研究者
Sanjeev Kumar
Sanjeev Kumar, MD, FRCPC
Centre for Addiction and Mental Health