The goal of this clinical trial is to learn if using deep repetitive transcranial magnetic stimulation (rTMS) targeting the precuneus is feasible, tolerable, and potentially efficacious for memory in Probable Alzheimer's Dementia. Previous work studying rTMS in Alzheimer's is mixed, but recent work studying rTMS of the precuneus is encouraging for both its short-term and long-term effects. The main questions this study aims to answer are:
* Is deep rTMS of the precuneus feasible and tolerable in Alzheimer's? * Are there signs of positive brain changes in response to deep rTMS? * Is deep rTMS potentially efficacious for memory in Alzheimer's? Researchers will compare active stimulation to placebo stimulation while obtaining memory testing and measurements of the brain (imaging, scalp electrode measurements, bloodwork) to see if active treatment works to treat mild-to-moderate probable Alzheimer's Dementia.
Participants will:
* Engage with memory testing, brain scans, and bloodwork during a comprehensive assessment * Visit the clinic 3 times for 12 consolidated rTMS sessions, followed by 4 once weekly maintenance sessions * Be offered a full open-label active treatment course after completing their treatment course if they are initially in the placebo group
Age 60-100 at the start of the study
Established diagnosis of Alzheimer's Clinical Syndrome (which is also met through a diagnosis of Alzheimer's Dementia)
Agreement to participate in study and able to complete informed consent process
Have a caregiver/study partner who can accompany them to all study visits
Participant and/or their surrogate are unwilling or unable to provide informed consent
Currently pregnant or potentially pregnant
Diagnosis of a dementia or cognitive disorder due to a cause other than Alzheimer's Disease
Diagnosis of severe Dementia (CDR > 2.0) at the start of the study
Parallel
TMS
DevicerTMS Stimulation Parameters Pulse count: 1600 pulses Frequency: 20Hz Pules per train: 40 pulses Inter-train interval: 28 seconds Intensity: 100% Motor Threshold (depth-corrected from MRI) Target: Precuneus using structural MRI navigation with MNI coordinates
Transcranial Magnetic Stimulation Sham
DeviceSham coil placed in same location and set with same parameters as active treatment coil. However, this device will not output active treatment and scalp electrodes will mimic the sensation of rTMS for the participant.
Completion Rate
The percentage/fraction of participants who complete the full course of study treatment
Adverse Events
The incidence of adverse events/side effects during the course of study treatment. Known common side effects of rTMS for other indications include discomfort/pain at the site of stimulation and mild transient headaches. Known rare though serious side effects include seizure (generally 1 in 30,000)
Gray Matter Volume
There are indications rTMS may preserve gray matter volume in neurodegenerative disease near the site of stimulation and connected areas. Volume of the precuneus, stimulated areas, and connected areas will be studied before and after treatment.
EEG
Beta and Gamma Oscillatory power, as well as Beta/Theta periodic power ratios will be examined.
NIH Cognitive Toolbox
The NIH Cognitive Toolbox consists of a battery of tests well-validated for memory testing. Participants will undergo testing with this tool before and after completing treatment.
Zarit Burden Index
The caregiver(s) of participants will complete this self-report measure of caregiver burden, with multiple versions available. It is one of the most widely-used and validated assessments of caregiver burden
Neuropsychiatric Inventory (NPI)
Participants and caregivers engage in comprehensive interview to assess the presence and severity of ten behavioral and two neurovegetative symptoms common in AD. This will aid in assessment of behavioral and emotional domains
ADL/IADL
Participants and caregivers engage in a discussion of participant's ability to complete and/or level of assistance needed to complete everyday tasks. This will aid in assessment of everyday function and overall dependence on others.
Peripheral Tau and Amyloid levels
Participants will undergo a blood draw for the purpose of determining peripheral Tau and Amyloid burden as a potential marker of AD pathology and allow researchers to explore potential changes with treatment.
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