A pilot randomized controlled double-blind trial of intermittent theta burst stimulation (iTBS) repetitive transcranial magnetic stimulation (rTMS) to improve memory in mild cognitive impairment (MCI): a study protocol
Abstract Background Mild cognitive impairment (MCI), prevalent among older adults, often precedes Alzheimer’s disease (AD) or Alzheimer’s disease-related dementias (ADRD), emphasizing the need for effective interventions. Early intervention in MCI is crucial, not only to alleviate symptoms but to po...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-04-01
|
| Series: | Pilot and Feasibility Studies |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40814-025-01625-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850269113773981696 |
|---|---|
| author | Maria I. Lapid Sandeep R. Pagali Michael R. Basso Paul E. Croarkin Jennifer R. Geske John Huston Karimul Islam Boney Joseph Walter W. Kennebeck Daehun Kang Simon Kung Allison M. LeMahieu Brian N. Lundstrom Ronald C. Petersen Mikaela M. Sarran Yunhong Shu Ilya M. Swanson Erik K. St. Louis Melissa K. Wang Yogatheesan Varatharajah Neeraj Wagh Kirk M. Welker Gregory A. Worrell Bradley F. Boeve |
| author_facet | Maria I. Lapid Sandeep R. Pagali Michael R. Basso Paul E. Croarkin Jennifer R. Geske John Huston Karimul Islam Boney Joseph Walter W. Kennebeck Daehun Kang Simon Kung Allison M. LeMahieu Brian N. Lundstrom Ronald C. Petersen Mikaela M. Sarran Yunhong Shu Ilya M. Swanson Erik K. St. Louis Melissa K. Wang Yogatheesan Varatharajah Neeraj Wagh Kirk M. Welker Gregory A. Worrell Bradley F. Boeve |
| author_sort | Maria I. Lapid |
| collection | DOAJ |
| description | Abstract Background Mild cognitive impairment (MCI), prevalent among older adults, often precedes Alzheimer’s disease (AD) or Alzheimer’s disease-related dementias (ADRD), emphasizing the need for effective interventions. Early intervention in MCI is crucial, not only to alleviate symptoms but to potentially delay the progression of cognitive decline. The lack of definitive treatments for MCI has prompted the exploration into alternative non-pharmacological therapeutic approaches. Specifically, noninvasive brain stimulation using repetitive transcranial magnetic stimulation (rTMS) has demonstrated promise in improving cognition in MCI and AD. Objectives Our study will test the feasibility of using intermittent theta burst stimulation (iTBS) technique of rTMS in MCI, pilot test the study design, and collect pilot data on the effect of iTBS over three different brain regions on working memory, new learning, and executive function in MCI. Exploratory objectives are to assess the feasibility and usefulness of functional magnetic resonance imaging (fMRI), high-density electroencephalography (HD-EEG), and sleep architecture as potential biomarkers in response to iTBS. Methods A pilot randomized double-blind controlled cross-over trial of iTBS on 20 MCI participants randomized to 10 days of active iTBS (left dorsolateral prefrontal cortex or left lateral parietal cortex) or control (vertex). After 4–6-week washout period, they cross over to the alternative treatment arm for another 10 days. Each participant will undergo a total of 20 iTBS sessions. Pre- and post-iTBS assessments include neuropsychological tests, fMRI, HD-EEG, and sleep architecture. Discussion This innovative study aims to test the feasibility of iTBS as a cognitive enhancement strategy in MCI. If our study is feasible, it could lead to a future larger trial to further test whether iTBS can modulate underlying neurobiology and offer a therapeutic avenue to remediate cognitive decline in MCI or ultimately delay progression to dementia. Trial registration ClinicalTrials.gov, NCT05327257. Registered 04 April 2022. |
| format | Article |
| id | doaj-art-c6b52bf537de4ed388ed5d09b60a9b65 |
| institution | OA Journals |
| issn | 2055-5784 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Pilot and Feasibility Studies |
| spelling | doaj-art-c6b52bf537de4ed388ed5d09b60a9b652025-08-20T01:53:15ZengBMCPilot and Feasibility Studies2055-57842025-04-0111111610.1186/s40814-025-01625-5A pilot randomized controlled double-blind trial of intermittent theta burst stimulation (iTBS) repetitive transcranial magnetic stimulation (rTMS) to improve memory in mild cognitive impairment (MCI): a study protocolMaria I. Lapid0Sandeep R. Pagali1Michael R. Basso2Paul E. Croarkin3Jennifer R. Geske4John Huston5Karimul Islam6Boney Joseph7Walter W. Kennebeck8Daehun Kang9Simon Kung10Allison M. LeMahieu11Brian N. Lundstrom12Ronald C. Petersen13Mikaela M. Sarran14Yunhong Shu15Ilya M. Swanson16Erik K. St. Louis17Melissa K. Wang18Yogatheesan Varatharajah19Neeraj Wagh20Kirk M. Welker21Gregory A. Worrell22Bradley F. Boeve23Department of Psychiatry and Psychology, Mayo ClinicDivision of Hospital Internal Medicine, Mayo ClinicDepartment of Psychiatry and Psychology, Mayo ClinicDepartment of Psychiatry and Psychology, Mayo ClinicDepartment of Quantitative Health Sciences, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Psychiatry and Psychology, Mayo ClinicDepartment of Quantitative Health Sciences, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Medicine Research, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Medicine Research, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Medicine Research, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicAbstract Background Mild cognitive impairment (MCI), prevalent among older adults, often precedes Alzheimer’s disease (AD) or Alzheimer’s disease-related dementias (ADRD), emphasizing the need for effective interventions. Early intervention in MCI is crucial, not only to alleviate symptoms but to potentially delay the progression of cognitive decline. The lack of definitive treatments for MCI has prompted the exploration into alternative non-pharmacological therapeutic approaches. Specifically, noninvasive brain stimulation using repetitive transcranial magnetic stimulation (rTMS) has demonstrated promise in improving cognition in MCI and AD. Objectives Our study will test the feasibility of using intermittent theta burst stimulation (iTBS) technique of rTMS in MCI, pilot test the study design, and collect pilot data on the effect of iTBS over three different brain regions on working memory, new learning, and executive function in MCI. Exploratory objectives are to assess the feasibility and usefulness of functional magnetic resonance imaging (fMRI), high-density electroencephalography (HD-EEG), and sleep architecture as potential biomarkers in response to iTBS. Methods A pilot randomized double-blind controlled cross-over trial of iTBS on 20 MCI participants randomized to 10 days of active iTBS (left dorsolateral prefrontal cortex or left lateral parietal cortex) or control (vertex). After 4–6-week washout period, they cross over to the alternative treatment arm for another 10 days. Each participant will undergo a total of 20 iTBS sessions. Pre- and post-iTBS assessments include neuropsychological tests, fMRI, HD-EEG, and sleep architecture. Discussion This innovative study aims to test the feasibility of iTBS as a cognitive enhancement strategy in MCI. If our study is feasible, it could lead to a future larger trial to further test whether iTBS can modulate underlying neurobiology and offer a therapeutic avenue to remediate cognitive decline in MCI or ultimately delay progression to dementia. Trial registration ClinicalTrials.gov, NCT05327257. Registered 04 April 2022.https://doi.org/10.1186/s40814-025-01625-5Noninvasive brain stimulationNeuromodulationCognitive enhancementMemory disorderCognitive declineDementia |
| spellingShingle | Maria I. Lapid Sandeep R. Pagali Michael R. Basso Paul E. Croarkin Jennifer R. Geske John Huston Karimul Islam Boney Joseph Walter W. Kennebeck Daehun Kang Simon Kung Allison M. LeMahieu Brian N. Lundstrom Ronald C. Petersen Mikaela M. Sarran Yunhong Shu Ilya M. Swanson Erik K. St. Louis Melissa K. Wang Yogatheesan Varatharajah Neeraj Wagh Kirk M. Welker Gregory A. Worrell Bradley F. Boeve A pilot randomized controlled double-blind trial of intermittent theta burst stimulation (iTBS) repetitive transcranial magnetic stimulation (rTMS) to improve memory in mild cognitive impairment (MCI): a study protocol Pilot and Feasibility Studies Noninvasive brain stimulation Neuromodulation Cognitive enhancement Memory disorder Cognitive decline Dementia |
| title | A pilot randomized controlled double-blind trial of intermittent theta burst stimulation (iTBS) repetitive transcranial magnetic stimulation (rTMS) to improve memory in mild cognitive impairment (MCI): a study protocol |
| title_full | A pilot randomized controlled double-blind trial of intermittent theta burst stimulation (iTBS) repetitive transcranial magnetic stimulation (rTMS) to improve memory in mild cognitive impairment (MCI): a study protocol |
| title_fullStr | A pilot randomized controlled double-blind trial of intermittent theta burst stimulation (iTBS) repetitive transcranial magnetic stimulation (rTMS) to improve memory in mild cognitive impairment (MCI): a study protocol |
| title_full_unstemmed | A pilot randomized controlled double-blind trial of intermittent theta burst stimulation (iTBS) repetitive transcranial magnetic stimulation (rTMS) to improve memory in mild cognitive impairment (MCI): a study protocol |
| title_short | A pilot randomized controlled double-blind trial of intermittent theta burst stimulation (iTBS) repetitive transcranial magnetic stimulation (rTMS) to improve memory in mild cognitive impairment (MCI): a study protocol |
| title_sort | pilot randomized controlled double blind trial of intermittent theta burst stimulation itbs repetitive transcranial magnetic stimulation rtms to improve memory in mild cognitive impairment mci a study protocol |
| topic | Noninvasive brain stimulation Neuromodulation Cognitive enhancement Memory disorder Cognitive decline Dementia |
| url | https://doi.org/10.1186/s40814-025-01625-5 |
| work_keys_str_mv | AT mariailapid apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT sandeeprpagali apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT michaelrbasso apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT paulecroarkin apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT jenniferrgeske apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT johnhuston apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT karimulislam apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT boneyjoseph apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT walterwkennebeck apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT daehunkang apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT simonkung apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT allisonmlemahieu apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT briannlundstrom apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT ronaldcpetersen apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT mikaelamsarran apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT yunhongshu apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT ilyamswanson apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT erikkstlouis apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT melissakwang apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT yogatheesanvaratharajah apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT neerajwagh apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT kirkmwelker apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT gregoryaworrell apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT bradleyfboeve apilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT mariailapid pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT sandeeprpagali pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT michaelrbasso pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT paulecroarkin pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT jenniferrgeske pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT johnhuston pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT karimulislam pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT boneyjoseph pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT walterwkennebeck pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT daehunkang pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT simonkung pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT allisonmlemahieu pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT briannlundstrom pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT ronaldcpetersen pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT mikaelamsarran pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT yunhongshu pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT ilyamswanson pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT erikkstlouis pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT melissakwang pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT yogatheesanvaratharajah pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT neerajwagh pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT kirkmwelker pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT gregoryaworrell pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol AT bradleyfboeve pilotrandomizedcontrolleddoubleblindtrialofintermittentthetaburststimulationitbsrepetitivetranscranialmagneticstimulationrtmstoimprovememoryinmildcognitiveimpairmentmciastudyprotocol |