This study aims to implement an intervention based on multiple, individualized multifocal tACS stimulation sessions based on individual PET and MRI information in patients with amyloid-positive PET with the hope that this leads to microglia activation and decrease in cerebral amyloid and tau depositions in human patients with AD.
This study will leverage all this accumulated knowledge by implementing an intervention based on multiple, individualized multifocal tACS stimulation sessions based on individual PET and MRI information in patients with amyloid-positive PET with the hope that this leads to microglia activation and decrease in cerebral amyloid and tau depositions in human patients with AD.This would have immense translational impact, as gamma tACS is an intervention that is portable, does not require expensive hardware, can be widely applied to large numbers of patients with AD, as well as, given its favorable side effect profile, even to patients at earlier stages of the disease who have cerebral amyloid/tau without clinical symptoms. The investigators aim to enroll 10 individuals with AD with evidence of increased cerebral amyloid burden on amyloid PET imaging. This would allow for a final sample size of 5-6 fully evaluable subjects. Each subject's participation in this study will consist of approximately 31-35 visits: 1 day for consent and screening procedures, 5-7 days of baseline procedures (this includes the PET scans), 20 tACS study visits, and 5-7 days of follow-up assessments. Subjects will undergo baseline cognitive assessment, structural and functional MRI characterization, PET imaging to assess amyloid burden, tau deposition and level of microglia activation, and resting-state EEG measurement. Additionally, subjects will undergo a TMS-EEG and a tACS-EEG recording session to assess brain plasticity levels and identify markers of response to stimulation. All subjects will subsequently undergo 20 sessions of gamma-frequency (40 Hz) tACS. At the end of the 20 sessions, subjects will then repeat the baseline assessments over 5-7 visits, including repeat PET imaging to assess for changes in amyloid burden, tau deposition, and microglia activation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
5
tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region.
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
PET Amyloid Burden
Changes in the amyloid load observed via PET imaging will be evaluated by comparing PET data acquired before and after the 20 tACS sessions. The metric used is standardized uptake value ratio (SUVR), a measure of the amount of proteins in the brain identified at the PET exam. We will calculate the difference between pre and post tACS SUVR for the entire brain and report the average value (and standard deviation) for the entire group of patients. A negative value express a decrease in the amount of proteins in the brain post tACS intervention.
Time frame: baseline and up to 12 weeks
PET Tau Deposition
Changes in the tau deposition observed via PET imaging will be evaluated by comparing PET data acquired before and after the 20 tACS sessions. The metric used is SUVR, a measure of the amount of proteins in the brain identified at the PET exam. We will calculate the difference between pre and post tACS SUVR (dSUVR) for the entire brain and report the average value (and standard deviation) for the entire group of patients. A negative value express a decrease in the amount of proteins in the brain post tACS intervention.
Time frame: up to 12 weeks
PET Microglia Activation
Changes in the microglia activation observed via PET imaging will be evaluated by comparing PET data acquired before and after the 20 tACS sessions. The metric used is SUVR, a measure of the amount of proteins in the brain identified at the PET exam. We will calculate the difference between pre and post tACS SUVR (dSUVR) for the entire brain and report the average value (and standard deviation) for the entire group of patients. A negative value express a decrease in the amount of proteins in the brain post tACS intervention.
Time frame: up to 12 weeks
Changes in Brain Perfusion as Measured by Arterial Spin Labeling
Patients underwent a comprehensive MRI exam before and after the tACS intervention, including measures of brain perfusion via Arterial Spin Labeling (ASL) sequences. The outcome measure represent the average change in perfusion (i.e. blood flow) recorded in regions targeted by tACS. Since Alzheimer's Disease is also characterized by a decrease of brain metabolism, an increased of blood flow after treatment would constitute a very promising sign of tACS efficacy in reducing Alzheimer's pathology in the brain. We will report the change in blood flow (mean, standard deviation) after tACS treatment.
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Time frame: 6 weeks (pre-post tACS intervention)