Effect of Modulating Gamma Oscillations Using tACS
Alzheimer Disease
About this trial
This is an interventional treatment trial for Alzheimer Disease focused on measuring Alzheimer Disease
Eligibility Criteria
Inclusion Criteria:
- Clinical Diagnosis of mild to moderate AD*
- Mini Mental State Examination (MMSE) > 18
- Mild AD ≥ 21
- Moderate AD 18-20
Demonstration or history of memory impairments.
* Confirmation of diagnosis will be made by the study MD based on a holistic consideration of the participant's cognitive evaluation and history.
- Amyloid positive PET imaging
- At least 45 years old
- On a stable dose of medications for memory loss including cholinesterase inhibitors (e.g. donepezil, rivastigmine or memantine) as defined as 6 consecutive weeks of treatment at an unchanging dose
- Minimum of completed 8th grade education
- IQ> 85 as determined by the WTAR and no history of intellectual disability
Exclusion Criteria:
- Current history of poorly controlled migraines including chronic medication for migraine prevention
- Current or past history of any neurological disorder other than dementia, such as epilepsy, stroke, progressive neurologic disease (e.g. multiple sclerosis) or intracranial brain lesions; and history of previous neurosurgery or head trauma that resulted in residual neurologic impairment.
- Past or current history of major depression, bipolar disorder or psychotic disorders, or any other major psychiatric condition.
- Contraindication for undergoing MRI or receiving TMS or tACS,
- >50 mSv of radiation exposure for research within the past year (PET imaging exclusion)
- Presence of the Thr/Thr polymorphism in the TSPO gene (rs6971) due to low affinity binding for the PBR 28 (microlgia) PET scan
- History of fainting spells of unknown or undetermined etiology that might constitute seizures.
- History of seizures, diagnosis of epilepsy, history of abnormal (epileptiform) EEG or immediate (1st degree relative) family history of epilepsy; with the exception of a single seizure of benign etiology (e.g. febrile seizure) in the judgment of the investigator.
- Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.).
- Metal implants (excluding dental fillings) or devices such as pacemaker, medication pump, nerve stimulator, TENS unit, ventriculo-peritoneal shunt, cochlear implant, unless cleared by the study MD.
- Substance abuse or dependence within the past six months.
- Medications will be reviewed by the responsible MD and a decision about inclusion will be made based on the following: The patient's past medical history, drug dose, history of recent medication changes or duration of treatment, and combination of CNS active drugs.
- All female participants that are pre-menopausal will be required to have a pregnancy test; any participant who is pregnant or breastfeeding will not be enrolled in the study.
- Subjects who, in the investigator's opinion, might not be suitable for the study
- A hair style or head dress that prevents electrode contact with the scalp or would interfere with the stimulation (for example: thick braids, hair weave, afro, wig)
Sites / Locations
- Beth Israel Deaconess Medical Center
Arms of the Study
Arm 1
Experimental
tACS
Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 20 sessions on consecutive weekdays. The tACS intervention (20 sessions) will be preceded and followed by amyloid, microglia and tau PET imaging as well as a clinical/cognitive evaluation. The assessment of the effect of stimulation on microglia activation, amyloid deposition and tau deposition will constitute a primary outcome measure. Assessment of adverse effects will be also evaluated as a secondary outcome. The effect of brain stimulation on brain connectivity will be assessed by EEG and MRI and cognitive function.