Suspected Non-Alzheimer Disease Pathophysiology (SNAP)
Conditions
Keywords
Suspected Non-Alzheimer Disease Pathophysiology (SNAP), theta-burst stimulation, repetitive transcranial magnetic stimulation (rTMS)
Brief summary
This is a pilot study to identify a homogeneous cohort of pathologically specific dementia with SNAP for clinical trial of brain stimulation.
Detailed description
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.
Interventions
DEVICEactive and active TBS
The investigators 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, The investigators will give two sessions of iTBS separated by 15 min.
DEVICEsham and active TBS
The investigators 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, The investigators will give two sessions of iTBS separated by 15 min. Sham stimulation applies the same iTBS protocol with the sham coil.
Sponsors
Chang Gung Memorial Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects aged 50-90 year. 2. 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). 3. Amyloid PET should ever be performed. 4. The CDR of subjects can be 0.5-2.
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. (cerebrovascular disorders, hydrocephalus and intra-cranial mass, documented by MRI; a history of traumatic brain injury or another neurological disease). 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 prolonged history of major psychiatric disorder like schizophrenia, bipolar disorder, and previously prolonged substances abuse. 5. Any females who is pregnant or lactating. 6. General MRI, TMS and/or PET
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The changes of Mini-Mental State Examination (MMSE) total scores | baseline (T0) and immediately after 2 weeks of TBS (T2), and 4 weeks of TBS (T4), and 8-week follow-up after TBS (T12) | The changes of Mini-Mental State Examination (MMSE) total scores (score range from 0 to 30, higher values represent a better cognitive outcome) |
| The changes of Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) total scores | baseline (T0) and immediately after 2 weeks of TBS (T2), and 4 weeks of TBS (T4), and 8-week follow-up after TBS (T12) | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The standard uptake values changes of FDG-PET | baseline (T0) and immediately after 2 weeks of TBS (T2), and 4 weeks of TBS (T4) | The standard uptake values (SUV) changes of cerebral glucose metabolism using 18F-FDG-PET |
Countries
Taiwan
Contacts
PRINCIPAL_INVESTIGATORKUAN YI WU
Chang Gung Memorial Hospital
Outcome results
None listed