Mild Cognitive Impairment
Conditions
Brief summary
This is an administrative supplement to an existing project Using fMRI-guided TMS to increase central executive function in older adults: NCT02767323 This award allows extending our existing fMRI-TMS paradigm to patients with a prodromal form of Alzheimer's Disease (AD) known as amnestic Mild Cognitive Impairment (MCI), and investigate the role of brain health factors in mediating the TMS-related memory performance benefits associated with communication between a network of frontoparietal brain regions in these populations. The focus on focal neurostimulation at only a single site represents a fundamental gap in the approach of memory-based neurostimulation therapies. Neurostimulation affects multiple sites within a cortical network, but these global effects have not been used as targets for stimulation because of limited knowledge about what influence these localized sites have on global changes in brain state. To address this problem, multimodal neuroimaging tools and network modeling approaches developed though the parent U01 project will be used, to demonstrate how focal neurostimulation improves the efficacy of TMS for enhancing memory function. These goals will be addressed in the Administrative Supplement under our two specific aims. First, network-guided TMS will be applied to optimize memory success based in the frontoparietal network (FPN) in a new group of MCI patients. A new form of TMS targeting that involves modeling of the global network to understand how the controllability of a stimulation site evokes changes in widespread brain networks will be tested. Second, structural and functional factors affecting the efficacy of individualized network-guided TMS will be identified to ameliorate deficits in MCI. By creating a multimodal model of neural deficits related to MCI, network-guided TMS will be adjusted to demonstrate how the MCI brain might compensate for these neural deficits. The parent U01 project has made foundational advances towards these goals, as we have demonstrated the ability of to selectively enhance and reduce working memory performance in healthy older adults. In the current Administrative Supplement this paradigm will be extended to a group of MCI participants in order to test the hypothesis that excitatory rTMS to the working memory network can provide positive outcomes for patients with pre-clinical AD. The proposed work will provide an important tool for studying the stability and controllability of network connectivity of memory states in the aging brain, as well as new information on the effectiveness of brain stimulation technologies as a therapeutic approach for cognitive decline.
Interventions
DEVICErTMS
excitatory 5Hz rTMS will be used
DEVICESham rTMS
an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used
Sponsors
National Institute on Aging (NIA)
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
55 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* English Speaking * willing to provide consent * signed HIPAA authorization * clinical consensus for MCI; and/or met inclusion criterial on MoCA, ApoE.
Exclusion criteria
* History of any I DSM IV disorder that is unstable or untreated * current or past history of substance abuse or dependence (excluding nicotine) * women who are pregnant or breast feeding * intracranial implants (e.g. aneurysms clips, shunts, stimulators, cochlear implants, or electrodes * increased risk of seizure for any reason, including prior diagnosis of epilepsy, seizure disorder, increased intracranial pressure, or history of significant head trauma greater than mild concussion (History of significant head trauma, including with loss of consciousness for ≥ 30 minutes, alteration of consciousness for up to 24 hours following the event, or post-traumatic amnesia) in the past 10yrs or head injury received after age 65 * Neurological disorder including, but not limited to: space occupying brain lesion; any history of seizures, history of cerebrovascular accident; cerebral aneurysm , Dementia, Huntington chorea, multiple sclerosis * Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), or currently taking medication that are on the strong potential hazard list for rTMS. * Subjects taking medications with an ACB score of 3.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute Effect of a rTMS Session on the Performance for a Working Memory Task, as Measured by Accuracy (in Percentage) | Through study completion, an average of one year | Accuracy (in percentage) will be assessed to evaluate the acute effect of rTMS. |
| Acute Effect of a rTMS Session on the Performance for a Working Memory Task, as Measured by Reaction Times (ms) | Through study completion an average of one year | Reaction times (in ms) will be assessed to evaluate the acute effect of rTMS |
Countries
United States
Participant flow
Pre-assignment details
Study was terminated prior to application of rTMS or Sham.
Participants by arm
| Arm | Count |
|---|---|
| Enrolled Participants The following numbers represent the baseline characteristics for the participants enrolled in the study, who performed only the behavioral task. None of these participants received rTMS | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Enrolled Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 65.2 years STANDARD_DEVIATION 6.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Acute Effect of a rTMS Session on the Performance for a Working Memory Task, as Measured by Accuracy (in Percentage)
Accuracy (in percentage) will be assessed to evaluate the acute effect of rTMS.
Time frame: Through study completion, an average of one year
Population: The study had to be interrupted because of Covid-19 situation, while we were still piloting the behavioral task. Therefore no data with rTMS were collected.
Primary
Acute Effect of a rTMS Session on the Performance for a Working Memory Task, as Measured by Reaction Times (ms)
Reaction times (in ms) will be assessed to evaluate the acute effect of rTMS
Time frame: Through study completion an average of one year
Population: The study had be be terminated early due to the Covid-19 situation, while we were still piloting the behavioral task. Therefore no participants received rTMS