Theta-burst Stimulation on Cognitive Function in the Patients With Young-onset Alzheimer's Disease Dementia

The Effects and Mechanisms of Theta-burst Stimulation on Cognitive Function in the Patients With Biomarker-defined Young-onset Alzheimer's Disease Dementia

Young-onset dementia (YOD) is a devastating condition, and it produces substantial psychosocial impacts on individual's functioning and family's care burden. Alzheimer's disease (AD) dementia is the most common type in YOD. Medication treatment Response was limited and unsatisfactory. In recent years, repetitive transcranial magnetic stimulation (rTMS) has been considered an alternative for the improvement of cognition in older patients with cognitive impairment. This study aims to examine the effects and potential mechanisms of theta-burst stimulation (TBS) on cognitive function in individuals with young-onset AD.

Study Overview

• Status: Enrolling by invitation
• Conditions: Alzheimer Disease, Early Onset
• Intervention / Treatment: Device: Theta-burst stimulation (TBS)

Detailed Description

The investigators apply the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria to recruit the biomarker-defined, young-onset AD patients with intermediate-to-high levels of biological evidence. This is a randomized, sham-controlled, 2-way crossover study, and combined neuroimaging study of 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to further explore the potential mechanisms. This study will consist of two intervention periods. A total of 50 young-onset AD patients will be consecutively recruited and be randomized into one of two groups: active and sham stimulation (n = 25 per group) in every intervention period. Besides, 20 cognitively normal subjects will be recruited for neuroimaging comparison. Cognitive evaluation will be performed before and immediately after treatment at 2 weeks of TBS intervention, and 4 weeks after TBS. Data on functional neuroimaging will be also collected before and after TBS protocol.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Guishan
    • Taoyuan District, Guishan, Taiwan, 333
      • Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Any patient has a definite diagnosis of AD dementia according to the NIA-AA criteria for intermediate-to-high levels of biological evidence of probable and possible AD dementia (McKhann et al. 2011).
2. Dementia onset before age 65 years old.
3. Age between 50-75 years old for patient and control group.
4. The severity of dementia is limited to mild to moderate stage in current project. The definition of mild to moderate stage of dementia is based on the clinical dementia rating scale (CDR) from 0.5-2.
5. Cognitively normal controls MMSE≧24, CDR should be 0.
6. Informed consent provided by the patient and family.

Exclusion Criteria:

1. Any subject has a definite diagnosis of epilepsy or history of seizure attack.
2. Current or past history of clinically significant neurological insults affecting brain structure or function like completed stroke, head injury or brain tumor.
3. Any subject has clinically significant or unstable medical diseases including metabolic, renal, liver, lung or cardiovascular disorders including metabolic, renal, liver, lung or cardiovascular disorders
4. Any subject has current alcohol or other substances abuse and/ or dependence within the recent one year, or previously prolonged history of substances abuse
5. Any females who is pregnant or lactating
6. General MRI, TMS and/or PET exclusion criteria including subjects who had received brain aneurysm surgery, or implanted pacemaker, mechanical valves, cochlear implant or other metal devices/ objects that are not magnetic resonance (MR) compatible in the body.
7. Any subject has allergic reaction to 18F-florbetapir or 18F-FDG radiotracers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active group; Active group will receive active stimulation of standard intermittent TBS (iTBS) protocol.	Device: Theta-burst stimulation (TBS); We will perform standard intermittent TBS (iTBS) parameters to left DLPFC of every patient in the study. The frequency parameters of TBS are 3-pulse 50-Hz bursts, every 200 ms at 5 Hz, and the intensity is 90% of active motor threshold. A single session of iTBS contains 2 s of TBS repeated every 10 s for 20 times. In this study, we will give two sessions of iTBS separated by 15 min.
Sham Comparator: Sham group; Sham group will receive sham stimulation of the same iTBS protocol with the coil set at 90 to the skull.	Device: Theta-burst stimulation (TBS); We will perform standard intermittent TBS (iTBS) parameters to left DLPFC of every patient in the study. The frequency parameters of TBS are 3-pulse 50-Hz bursts, every 200 ms at 5 Hz, and the intensity is 90% of active motor threshold. A single session of iTBS contains 2 s of TBS repeated every 10 s for 20 times. In this study, we will give two sessions of iTBS separated by 15 min.
No Intervention: Cognitively normal control; Cognitively normal controls will be recruited for neuroimaging comparison.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline MMSE total scores immediately after TBS intervention	The changes of Mini-Mental State Examination (MMSE) total scores (score range from 0 to 30, higher values represent a better cognitive outcome)	Before and immediately after TBS intervention
Change from baseline MMSE total scores 4 weeks after TBS intervention	The changes of Mini-Mental State Examination (MMSE) total scores (score range from 0 to 30, higher values represent a better cognitive outcome)	Before and 4 weeks after TBS intervention
Change from baseline ADAS-Cog total scores immediately after TBS intervention	The changes of Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) total scores (score range from 0 to 70, higher score indicates a worse cognitive outcome)	Before and immediately after TBS intervention
Change from baseline ADAS-Cog total scores 4 weeks after TBS intervention	The changes of Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) total scores (score range from 0 to 70, higher score indicates a worse cognitive outcome)	Before and 4 weeks after TBS intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The standard uptake values changes of FDG-PET	The standard uptake values (SUV) changes of cerebral glucose metabolism using 18F-FDG-PET	Before and 1 week after TBS intervention

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: KUAN YI WU, Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: July 28, 2019
• First Submitted That Met QC Criteria: July 31, 2019
• First Posted (Actual): August 2, 2019

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Alzheimer's disease; rTMS; TBS; Young-onset dementia
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: 201802104A0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No