Transcranial Alternating Current Stimulation to Engage Theta-Gamma Coupling and Enhance Working Memory in Patients With Mild Cognitive Impairment
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Percentage of All Screened Participants
研究概览
简要总结
This study is looking at a new non-invasive brain stimulation methods called transcranial alternating current stimulation (tACS) to see if it can improve working memory and thinking processes in people with Mild Cognitive Impairment (MCI). tACS is a low-risk, non-painful, low electrical current that circulates through the brain of awake participants and stimulates their brain cells. Participants must be 60 years of age and have a diagnosis of mild cognitive impairment. Participants will undergo treatment sessions that range from 1 to 1.5 hours at CAMH, 5 days a week, over a total of 2 weeks. In addition, participants will complete clinical and cognitive assessments and bloodwork at baseline and again after treatment.
详细描述
Current treatments for Alzheimer's disease dementia (AD) have limited efficacy probably because by the time AD is manifest it is too late to intervene. Thus, discovering interventions that will prevent AD is highly needed.
Mild Cognitive Impairment (MCI) is a condition that is considered a pre-stage to AD. In MCI, the frontal part of the brain supports the ability to compensate for memory problems which could delay progression to AD. This compensation is supported by "flexible" thinking which includes the ability to hold and manipulate information in mind for brief periods of time (e.g. doing mental math), also called working memory. Working memory has been shown by us and others to depend on the linking of brain waves across multiple brain waves frequencies.
Transcranial Alternating Current Stimulation (tACS) is a non-invasive electrical stimulation, applied to the scalp, that has been shown to improve this linking of brain waves in healthy older individuals. It has also been shown to enhance working memory in older individuals when this linking is enhanced. The effect of tACS on working memory and linking of brain waves in patients with MCI has not been demonstrated yet.
The study investigators propose to study the feasibility and preliminary effects of tACS on TGC and working memory in MCI participants. This proof-of-concept study will test whether tACS engages TGC as a target and, in turn, enhances working memory. Additionally, the investigators will explore the relationship among tACS effects and stress neuroreactivity and neuroimmune/inflammatory response (i.e., the interaction between the nervous system and the immune system), as well as the potential links with working memory.
If successful, our project will serve as a model for a larger trial to confirm the ability of tACS to prevent AD over multiple years of follow-up.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The study will be completed under triple-blind conditions. First, participants will be blind to whether they are randomized to the active treatment (tACS) or sham group (sham-tACS), which is achievable because it is difficult to distinguish the active treatment interventions from the control conditions. Second, the investigator team (investigators and interventionists delivering the 10-session course) will be blind to group assignment. Third, the outcomes assessors conducting the clinical, cognitive and EEG assessments at baseline and follow-ups will be blind to group assignment.
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 60 years or above,
- •Diagnosis of MCI due to AD using the core clinical criteria by the National Institute on Aging and Alzheimer's Association for MCI participants (NIA-AA) and ascertained by a study investigator. The following checklist will be used to ascertain the MCI diagnosis:
- •Cognitive concern reflecting a change in cognition reported by patient or informant or clinician (i.e., historical or observed evidence of decline over time)
- •Not demented ascertained using the study investigator opinion.
- •No vascular, traumatic, or medical causes of cognitive decline ascertained using the study investigator opinion.
- •Evidence of longitudinal decline in cognition, when feasible, and ascertained using the study investigator opinion.
- •Objective evidence of single or multi domain MCI, where single domain MCI refers to deficits using neuropsychology (NP) battery on only one of the cognitive domains (Speed of Processing; Working Memory; Executive Functioning; Verbal Memory; Visual Memory; Language) and multi domain MCI refers to deficits in more than one of these domains. To determine impairment in one or more cognitive domain, after the NP battery is administered and double scored, a consensus meeting will be held with the Research Analyst/Fellow, the study Principal Investigator and the study Neuropsychologist during which eligibility will be discussed. The meeting attendees will take into consideration the participant's education, parental education, pre-morbid IQ, physician's assessment and NP scores to determine if the participant has impairment in one or more cognitive domain.
- •Willingness to provide informed consent,
- •Ability to read and communicate in English (with corrected vision and hearing, if needed)
排除标准
- •Current use of an acetylcholine esterase inhibitor or memantine ascertained via participant's report, Medication List, or Electronic Medical Record (EMR).
- •Major Depressive Disorder with active symptoms in the last 3 months ascertained using the Mini International Neuropsychiatric Interview (MINI), or Structured Clinical Interview for DSM-5 (SCID), or EMR.
- •A lifetime diagnosis of bipolar disorder; intellectual disability; or a psychotic disorder ascertained using the MINI or SCID, or EMR.
- •Substance use disorder active in the last 3 months ascertained using the MINI or SCID, or EMR.
- •Any other DSM-5 diagnosis ascertained using the MINI or SCID, or EMR, that may be associated with prefrontal cortical dysfunction as ascertained using a study investigator opinion.
- •Current anticonvulsant use due to its impact on brain stimulation induced activity and ascertained using a Medication List or EMR. An exception will be made if they are taking gabapentin or pregabalin AND if the dose had been stable for at least 4 weeks prior to study entry AND if prescribed for chronic pain.
- •Current benzodiazepine use of more than what is equivalent to lorazepam 2 mg/day as ascertained using a Medication List. This is due to their known pro-GABAergic activity and the suppressive effect of GABAergic agents on cortical plasticity
- •Any contraindication to MRI or contraindication to tACS (e.g., cardiac pacemaker, acoustic device, history of seizures) ascertained using the tACS Safety Screen (tSS)
研究组 & 干预措施
Active tACS
After completing the Baseline testing at Visit 1 and N-back EEG at Visit 2, MCI participants randomized to the active condition will receive a 10-session course of tACS (Visits 4-13), followed by a follow-up assessment, post intervention, at Visit 14.
干预措施: Transcranial Alternating Current Stimulation (Device)
Sham tACS
After completing the Baseline testing at Visit 1 and N-back EEG at Visit 2, MCI participants randomized to the sham condition will receive a 10-session course of sham-tACS (Visits 4-13), followed by a follow-up assessment, post intervention, at Visit 14.
干预措施: Sham tACS (Device)
结局指标
主要结局
Percentage of All Screened Participants
时间窗: Through treatment completion, at the end of 2-week intervention.
Recruitment (percentage of all screened participants) will be examined. Hypothesis: At least 30% of screened participants will agree and be eligible to receive the intervention they are assigned to, i.e., tACS.
Percentage of All Enrolled Participants
时间窗: Through treatment completion, at the end of 2-week intervention.
Retention will be examined. Hypothesis: At least 70% of participants will attend at least 80% of their treatment sessions.
次要结局
- Mediation of TGC on changes in N-back performance(Through treatment completion, at the end of 2-week intervention.)
- Theta-gamma Coupling(Through treatment completion, at the end of 2-week intervention.)
- N-Back(Through treatment completion, at the end of 2-week intervention.)