Clinical trial NCT05515952: Interleaved TMS-fMRI for Hippocampal Stimulation: Modeling Dose-Response Relationship in Amnestic Mild Cognitive Impairment
Official title: Interleaved TMS-fMRI for Hippocampal Stimulation: Modeling Dose-Response Relationship in Amnestic Mild Cognitive Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mild Cognitive Impairment
Keywords: Mild Cognitive Impairment
Transcranial Magnetic Stimulation
Lead sponsor: University of Arizona
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2022-08-25
Enrollment: 20
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Brain imaging data
timeFrame: Baseline
measure: Correction rate in memory association recall
timeFrame: Baseline
Secondary outcomes:
measure: Brain imaging data
timeFrame: immediately after and 24 hours after intervention
measure: Correction rate in memory association recall
timeFrame: immediately after and 24 hours after intervention
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Bioscience Research Laboratory
state: Arizona
Study officials:
affiliation: University of Arizona
name: Ying-hui Chou, ScD
role: PRINCIPAL_INVESTIGATOR
References: