Cognitive Effects of Theta-burst Stimulation (TBS) in Suspected Non-Alzheimer Disease Pathophysiology (SNAP)

The investigators apply the NIA-AA criteria to identify the individuals of biomarker-defined SNAP endophenotype. This is a prospective, randomized controlled clinical trial for the first two weeks, followed by an open-label trial for the next two weeks, and combined functional neuroimaging study of 18F-FDG-PET to further explore the potential mechanisms. A total of 20 SNAP dementia patients will be recruited for consecutive two years, and be subjected to iTBS for 5 daily interventions per week for four consecutive weeks. Cognitive evaluation will be performed before and immediately after TBS intervention, and 8 weeks after TBS. Data on functional neuroimaging will be also collected before and after TBS protocol.

Inclusion criteria

• Subjects aged 50-90 year.
• Patients meet NIA-AA research criteria for suspected non-Alzheimer disease pathophysiology (SNAP) (Petersen, Smith et al. 1999; Jack, Bennett et al. 2018), and DSM-5 criteria for major neurocognitive disorder of dementia (Regier, Narrow et al. 2013).
• Amyloid PET should ever be performed.
• The CDR of subjects can be 0.5-2.

Exclusion criteria

• Any subject has a definite diagnosis of epilepsy or history of seizure attack.
• Current or past history of clinically significant neurological insults affecting brain structure or function like completed stroke, head injury or brain tumor. (cerebrovascular disorders, hydrocephalus and intra-cranial mass, documented by MRI; a history of traumatic brain injury or another neurological disease).
• 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.
• Any subject has current alcohol or other substances abuse and/ or dependence within the recent one year, or prolonged history of major psychiatric disorder like schizophrenia, bipolar disorder, and previously prolonged substances abuse.
• Any females who is pregnant or lactating.
• 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 MR compatible in the body.

Withdrawal criteria

• Complications onset after intervention that affect efficacy and safety judgments.
• New onset or progression of disease that may affect outcomes.
• Use of other therapies or drugs during the intervention period to change cognitive functions.
• Any subjects who are recognized as high risk of adverse effects by principle investigator.