Enhancing Frontal Lobes Plasticity in Mild Cognitive Impairment

Last updated on July 2021

Recruitment

Recruitment Status: Recruiting
Estimated Enrollment: Same as current

Summary

Conditions

Memory Impairment
Mild Cognitive Impairment

Type

Interventional

Phase

Not Applicable

Design

Allocation: RandomizedIntervention Model: Parallel AssignmentIntervention Model Description: At screening 100 MCI and 50 HC participants will undergo clinical and cognitive assessments and a brain MRI to localize the DLPFC. If eligible, at baseline, all participants will undergo N-back and PAS-EEG to assess baseline DLPFC plasticity. Following baseline procedures, MCI participants will be randomized (1:1) to the study intervention consisting of 10 sessions of either bilateral PAS or PAS-C to the right and left DLPFC, 1 session/day, for 10 days. On the last day of the intervention, participants will repeat the cognitive assessments and on the following day they will repeat N-back and PAS-EEG to assess the effect of daily PAS on executive function and DLPFC plasticity. Finally, on the 7th day following the intervention, MCI participants will repeat N-back and PAS-EEG, and on the 28th and 29th day following the intervention, MCI participants will repeat the cognitive assessments, N-back and PAS-EEG to evaluate the sustainability of effects.Masking: Triple (Participant, Investigator, Outcomes Assessor)Masking Description: A unique advantage of Paired Associative Stimulation (PAS) over other TMS-based interventions is that its control condition (PAS-C) is almost impossible to distinguish from active PAS. Thus, the RCT phase of the study will be completed under triple-blind conditions. First, participants will be blind to whether they are randomized to PAS or PAS-C. 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 PAS-EEG assessments at baseline and follow-ups will be blind to group assignment.Primary Purpose: Treatment

Participation Requirements

Age: Between 60 years and 125 years
Gender: Both males and females

Description

Paired Associative Stimulation (PAS) is a neurostimulation approach that induces cortical plasticity by simulating spike-timing-dependent plasticity. Combining PAS with electroencephalography (EEG) (PAS-EEG), we can assess dorsolateral prefrontal cortex (DLPFC) plasticity in vivo. Using PAS-EEG, we have demonstrated that patients with AD are impaired on DLPFC plasticity compared to healthy control (HC) individuals and that DLPFC plasticity is associated with working memory in AD and HC individuals. We have also shown that a 2-week course of daily PAS to the left DLPFC restores DLPFC plasticity in patients with AD and enhances their working memory. Thus, we propose to study DLPFC plasticity and its relationship to executive function in MCI and then assess the efficacy of a 2-week course of PAS in enhancing DLPFC plasticity and executive function in this population. If successful, this project will identify a novel neurostimulation intervention (PAS) to enhance prefrontal cortical function in MCI patients. This enhancement could result in modifying the trajectory of Alzheimer's disease by delaying the progression from MCI to clinical AD. This project will also identify a mechanism (neuroplasticity) that underlies enhanced prefrontal cortical function. Other interventions (e.g. behavioral, neurostimulation, pharmacological) could then be tested whether they engage neuroplasticity to enhance prefrontal cortical function. The primary objectives and hypotheses of the study are as follows: Objective 1: To compare baseline DLPFC plasticity and its relationship to executive function in MCI vs. HC participants. Hypothesis 1a: MCI participants will be impaired on PAS-LTP (TMS-induced cortical evoked activity) in the left DLPFC compared to HC participants. Hypothesis 1b: MCI participants will be impaired on 2-back d' and a composite executive function measure compared to HC participants. Hypothesis 1c: PAS-LTP will be associated with 2-back d' and composite executive function measure in MCI and HC participants after controlling for age, sex, and education. Objective 2: To assess the efficacy of a 10-session course of bilateral PAS in enhancing DLPFC plasticity and executive function in MCI participants. Hypothesis 2a: MCI participants randomized to 10-session course of active PAS will experience higher PAS-LTP in the left DLPFC immediately and 1 and 4 weeks after the course compared to MCI participants randomized to a 10-session course of a sham control PAS condition (PAS-C). Hypothesis 2b: MCI participants randomized to a 10-session course of active PAS will experience better 2-back performance and higher composite executive function immediately and 1 and 4 weeks following the 10-session course compared to MCI participants randomized to the course of PAS-C. Objective 3: To assess whether changes in DLPFC plasticity mediate changes in executive function in MCI participants following the 10-session course. Hypothesis 3: Changes in PAS-LTP immediately and 1 and 4 weeks following the 10-session course will mediate changes in 2-back d' and composite executive function measure at all three follow-up time points.

Tracking Information

NCT #: NCT04583215
Collaborators: Not Provided
Investigators: Principal Investigator: Tarek Rajji, MD Centre for Addiction and Mental Health