Alzheimer Disease
Conditions
Keywords
transmagnetic stimulation, functional MRI guided Theta Burst Stimulation, Early Stage
Brief summary
Alzheimer's disease (AD) is a progressive neurodegenerative condition affecting 6.2 million individuals in the United States, resulting in an annual cost of care of $305 billion. AD is functionally characterized by progressive degeneration of large-scale brain networks (LSBNs), including the default mode network (DMN) presumably from the deposition of amyloid plaques and neurofibrillary tangles. Available FDA-approved medications for AD such as donepezil and memantine offer limited benefit and modest impact on quality of life. In combination with resting state functional MRI (rs-fMRI), transcranial magnetic stimulation (TMS) with intermittent theta burst stimulation (iTBS) offers a non-invasive alternative to pharmacotherapy in persons with AD. We propose a pilot trial using rs-fMRI to target dysfunctional LSBNs in early stage AD.
Interventions
DEVICEIntermittent theta burst stimulation
MagVenture TMS Therapy with theta burst stimulation. Resting motor threshold: 80%; Number of pulses per session: 1200 pulses; Inter-train interval: 8 seconds; Pulse frequency in burst: 50 Hertz
Sponsors
HealthPartners Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Established diagnosis of Mild Cognitive Impairment (MCI)/mild AD * Evidence for Central Nervous System (CNS) amyloidosis (e.g., Amyloid positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers consistent with AD) * Prior brain imaging performed * Mini-Mental State Examination (MMSE) \>24 * Clinical Dementia Rating (CDR) Scale 0.5-1 * Stable dose of cholinesterase inhibitors and memantine for at least one month * Subjects are between 40-90 years of age
Exclusion criteria
* Non-AD dementia including, but not limited to, Lewy body dementia, frontotemporal dementia, vascular dementia, Jakob-Creutzfeldt disease, etc. * Inability to tolerate rs-fMRI * Contraindication of rs-fMRI due to implants or metal * Seizure disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Connectivity Measure of the TGd Parcellations. | 9 weeks | Assessed by calculating the difference and standard deviation between follow-up and baseline of number of abnormal connections of the TGd parcellation. Range: 0-378. There are 378 possible connections of the parcellation. Higher values indicate more abnormal connections of the TGd parcellation pre and post-treatment. The change in the number of abnormal connections of the parcellation is reported. |
Countries
United States
Participant flow
Pre-assignment details
4 participants screen failed with a low MMSE, 1 participant withdrew before receiving any treatment.
Participants by arm
| Arm | Count |
|---|---|
| Intermittent Theta Burst Stimulation All subjects will receive treatment with intermittent theta burst stimulation (iTBS). There will be a total of 5 treatments over a 2-week period. All subjects will receive iTBS to the right TGd region. TBS treatment will also be provided for two additional sites within the large-scale brain networks (LSBNs) that is found to contain the greatest number of connectivity anomalies. Total participation will be 10-12 weeks.
Intermittent theta burst stimulation: MagVenture TMS Therapy with theta burst stimulation. Resting motor threshold: 80%; Number of pulses per session: 1200 pulses; Inter-train interval: 8 seconds; Pulse frequency in burst: 50 Hertz | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Intermittent Theta Burst Stimulation |
|---|---|
| Age, Continuous | 67.6 years STANDARD_DEVIATION 8.5 |
| Clinical Dementia Rating (CDR) Scale | 0.5 units on a scale STANDARD_DEVIATION 0 |
| Education Level Bachelors/Associates | 6 Participants |
| Education Level Masters/PhD | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Mini Mental Status Examination (MMSE) | 26.3 units on a scale STANDARD_DEVIATION 1.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 10 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Change in Connectivity Measure of the TGd Parcellations.
Assessed by calculating the difference and standard deviation between follow-up and baseline of number of abnormal connections of the TGd parcellation. Range: 0-378. There are 378 possible connections of the parcellation. Higher values indicate more abnormal connections of the TGd parcellation pre and post-treatment. The change in the number of abnormal connections of the parcellation is reported.
Time frame: 9 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intermittent Theta Burst Stimulation | Change in Connectivity Measure of the TGd Parcellations. | 0.5 abnormal connections | Standard Deviation 25 |