Mild Cognitive Impairment
Conditions
Keywords
Mild Cognitive Impairment, Transcranial Magnetic Stimulation
Brief summary
Emerging evidence indicates that dysfunction of hippocampal synaptic plasticity, which precedes neuronal degeneration during the progression of Alzheimer's disease (AD), underlies the hallmark cognitive impairment. Although there are currently no effective disease modifying treatments for AD, recent preclinical studies in animal models of AD have suggested that repetitive transcranial magnetic stimulation (rTMS) promotes hippocampal synaptic plasticity and, ultimately, improves learning and memory abilities. Interleaved TBS-MRI is a paradigm, which allows the investigators to study human brain functionality with real-time MRI, to better understand modulations of brain activity in response to the non-invasive brain stimulation, TBS. The interleaved TBSfMRI paradigm can more accurately estimated the immediate brain activity compared to the offline TBS-MRI studies in which TBS is applied outside the MRI. With this interleaved TBS-MRI approach, the investigators will be able to measure immediate changes in targeted brain activity, such as hippocampus activation, following each TBS session. This approach has created the unprecedented potential enabling the investigators to model the dose-dependent effects of TBS more accurately on brain function.
Detailed description
The overarching goal of this proposed project is to maximize TBS effects to non-invasive spaced TBS in MCI. For the comparison, the investigators will include cognitively normal adults. There will be a screening session plus three consecutive days including baseline outcome measures on Day 1, TMS interventions and outcome measures on Day 2, and follow-up measurements on Day 3. In this project, on Day 2, participants will receive three TBS blocks inside the MRI scanner with each TBS block separated by 30-90 minutes to enhance the possibility of maximizing the TBS effect. This will be repeated in two blocks, each with a different TMS protocol. The protocols will be in randomized order.
Interventions
DEVICETranscranial Magnetic Stimulation
TMS is a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect on the hippocampus and determine which stimulation protocol is more beneficial to each participant.
TMS is a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect on the hippocampus and determine which stimulation protocol is more beneficial to each participant. For sham, the side of the coil that does not deliver pulses will be used.
Sponsors
National Institute on Aging (NIA)
University of Arizona
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 50-80 years * MCI clinical criteria: (a) self- or informant-reported cognitive complaint; (b) preserved independence in functional abilities; and (c) absence of dementia. * Objective cognitive impairment supported by the following measures of general cognitive function: (a) Mini-Mental State Exam (MMSE) 24-27 (inclusive); (b) Montreal Cognitive Assessment (MoCA) 18-26 (inclusive); or (c) Clinical Dementia Rating Scale score of 0.5. * Right handed * English speaking * Able to attend daily intervention (Monday-Friday) for 4 days * Not enrolled in another interventional study within 6 months prior to beginning this study
Exclusion criteria
* Contraindications to transcranial magnetic stimulation (TMS) or magnetic resonance imaging (MRI) * Other neurological disorders (e.g. stroke, head injuries, or multiple sclerosis) * Untreated depression * Current cancer treatment or other medical problems that might independently affect cognitive function * Clinical Dementia Rating Scale score more than 1.0
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correction Rate in Memory Association Recall | Immediately after intervention day (block 1 day 2) and (block 2 day 2) vs. Baseline | Memory tasks will be implemented and measure the correct rate to assess memory function. The scale is the Face Name Associated Memory Score, and the min/max values are 0-1. A higher score indicates a better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active TBS-Sham TBS Active TBS in block one, Sham TBS in block two
Transcranial Magnetic Stimulation: TMS is a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect on the hippocampus and determine which stimulation protocol is more beneficial to each participant.
Transcranial Magnetic Stimulation (Sham): TMS is a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect on the hippocampus and determine which stimulation protocol is more beneficial to each participant. For sham, the side of the coil that does not deliver pulses will be used. | 11 |
| Sham TBS-Active TBS Sham TBS in block one, Active TBS in block two
Transcranial Magnetic Stimulation: TMS is a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect on the hippocampus and determine which stimulation protocol is more beneficial to each participant.
Transcranial Magnetic Stimulation (Sham): TMS is a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect on the hippocampus and determine which stimulation protocol is more beneficial to each participant. For sham, the side of the coil that does not deliver pulses will be used. | 9 |
| Total | 20 |
Baseline characteristics
| Characteristic | Active TBS-Sham TBS | Sham TBS-Active TBS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 6 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 3 Participants | 8 Participants |
| Age, Continuous | 67.82 years STANDARD_DEVIATION 8.73 | 66.42 years STANDARD_DEVIATION 4.64 | 67.19 years STANDARD_DEVIATION 7.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 8 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 9 Participants | 20 Participants |
| Region of Enrollment United States | 11 participants | 9 participants | 20 participants |
| Sex: Female, Male Female | 9 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 0 / 22 | 1 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
Correction Rate in Memory Association Recall
Memory tasks will be implemented and measure the correct rate to assess memory function. The scale is the Face Name Associated Memory Score, and the min/max values are 0-1. A higher score indicates a better outcome.
Time frame: Immediately after intervention day (block 1 day 2) and (block 2 day 2) vs. Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active TBS | Correction Rate in Memory Association Recall | .106 units on a scale | Standard Deviation 0.097 |
| Sham TBS | Correction Rate in Memory Association Recall | .031 units on a scale | Standard Deviation 0.083 |