Theta-burst Stimulation on Cognitive Function in the Patients with 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.

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.

Eligibility Criteria:
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.