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Mild cognitive impairment (MCI) is a precursor of dementia. Apathy, a profound loss of motivation, is a common behavioral problem in MCI. Presence of apathy may increase the chance of MCI patients converting to Alzheimer's Dementia. Repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive tool, has been recently approved for treatment of refractory depression. Since dysfunction in the frontal lobe of the brain is seen in patients with apathy, rTMS to the frontal lobe might be helpful in treating the same. Study hypotheses include that rTMS to the dorsolateral prefrontal cortex (DLPFC) will improve apathy and executive function better than sham treatment in those with MCI
Objective: Mild cognitive impairment (MCI) is a precursor of dementia. Apathy, a profound loss of motivation, is a common behavioral problem in MCI. Presence of apathy may increase the chance of MCI patients converting to Alzheimer's Dementia. Repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive tool, has been recently approved for treatment of refractory depression. Since dysfunction in the frontal lobe of the brain is seen in patients with apathy, rTMS to the frontal lobe might be helpful in treating the same.
Specific Aims:
Research Plan: Current study is a randomized sham controlled cross-over study of daily rTMS.
Methods: 20 subjects with MCI and apathy will be enrolled to randomize 8 to a total of 20 sessions of treatment (2 weeks sham, 2 weeks rTMS, with 4 weeks of washout period). Subjects will be randomly assigned to rTMS or sham treatment after consent. After 2 weeks of treatment there will be a 4 week period with no treatment. At the end of the 4-week wash out period, subjects will be crossed over to the next treatment arm (i.e. those who received rTMS in the beginning will receive sham treatment and vice versa). Subjects will be followed for four additional weeks after treatment. Apathy will be assessed using the Apathy Evaluation Scale. Memory, executive function, functional status and caregiver burden will be assessed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| transcranial magnetic stimulator | Active Comparator | Neurostar repetitive transcranial magnetic stimulator. The active procedure will stimulate at 120% motor threshold for 4 seconds at a frequency of 10 Hz, with an inter-train interval of 26 seconds for a total of 3,000 pulses. 10 treatment sessions are given over a two week period. |
|
| Sham coil treatment | Sham Comparator | Neurostar repetitive transcranial magnetic stimulator. 10 treatments identical in duration will be administered over a two week period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Neurostar repetitive transcranial magnetic stimulator | Device | The active procedure will stimulate at 120% motor threshold for 4 seconds at a frequency of 10 Hz, with an inter-train interval of 26 seconds for a total of 3,000 pulses. 10 treatment sessions are given over a two week period. |
| Measure | Description | Time Frame |
|---|---|---|
| Apathy Evaluation Scale (AES) | AES is an 18-item scale that assesses apathy in behavioral, cognitive and emotional domains over the previous four weeks. | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Trials making test | Widely used test for assessment of executive function. | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Exit 25 | EXIT-25 is a bedside measure of executive function. It defines the behavioral sequelae of executive dyscontrol and provides a standardized clinical encounter in which they can be observed. | 8 weeks |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Prasad R Padala, MD, MS | Central Arkansas Veterans Healthcare System | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Central Arkansas Veterans Healthcare System | Little Rock | Arkansas | 72205 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29331848 | Derived | Padala PR, Padala KP, Lensing SY, Jackson AN, Hunter CR, Parkes CM, Dennis RA, Bopp MM, Caceda R, Mennemeier MS, Roberson PK, Sullivan DH. Repetitive transcranial magnetic stimulation for apathy in mild cognitive impairment: A double-blind, randomized, sham-controlled, cross-over pilot study. Psychiatry Res. 2018 Mar;261:312-318. doi: 10.1016/j.psychres.2017.12.063. Epub 2018 Jan 5. |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Jan 23, 2018 | |
| Reset | Mar 1, 2018 | |
| Release | Aug 20, 2019 | |
| Reset | Sep 12, 2019 | |
| Release | Jul 13, 2020 | |
| Reset | Jul 24, 2020 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Jan 23, 2018 | Mar 1, 2018 | |||
| Aug 20, 2019 |
| ID | Term |
|---|---|
| D053609 | Lethargy |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
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| Sep 12, 2019 |
| Jul 13, 2020 | Jul 24, 2020 |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |