Using deep rTMS to improve memory in Alzheimer's Disease

Inclusion Criteria:

* Agreement to participate in study and able to complete informed consent process
* Have a caregiver or study partner who can accompany them to all study visits
* Have a known alternate surrogate decision-maker (in case needed) who can be present for informed consent
* Established diagnosis of biomarker-positive (amyloid-PET, plasma or CSF amyloid ratio or phosphorylated tau) mild-moderate (clinical stages 3, 4, and 5) Alzheimer's Disease based on the 2024 Alzheimer's Association Framework
* Age 55-100 at the start of the study.
* Screening MOCA 12-25 (\< 26, \> 11)
* Screening GDS score \<6
* Either 1) treated with memory-enhancing medication (cholinesterase inhibitor or other medications or treatments) for at least 2 months, 2) failed trial with no plan to re-trial, or 3) no trial planned during the course of the study for other reasons
* No change in use of psychotropic medication (or other treatments) for the treatment of depression, anxiety, ADHD, or psychosis for 2 weeks prior to the study

Exclusion Criteria:

* Unwilling or unable to provide informed consent as outlined below
* Currently pregnant or potentially pregnant
* Diagnosis of a dementia or cognitive disorder primarily or exclusively due to a cause other than Alzheimer's Disease
* Diagnosis of severe Dementia (CDR \> 2.0/ AA clinical stage 6) at the start of the study
* History of substance use disorder currently not in sustained remission
* Substance misuse within the past 6 months (excluding nicotine or caffeine)
* History of stroke, traumatic brain injury with loss of consciousness, or other major neurologic disorder (e.g., epilepsy, Huntington's disease, Parkinson's disease)
* History of seizure disorder or family history of seizure disorder in a first-degree relative
* Poorly-controlled hypertension, cardiovascular disease, or cerebrovascular disease
* History of any other major active medical, neurologic, or psychiatric illness affecting cognition (associated with cognitive impairment) or a participant's ability to safely and meaningfully participate in the study
* Non-fluent in English (not native or functionally-native, specified here for cognitive testing purposes)
* Contraindication to TMS or MRI including claustrophobia, MRI-incompatible or unknown metal in body (including facial tattoos with uknown or metallic inks), surgery within 60 days, certain implants (excluding dental fillings), or previous abnormal MRI results unrelated to a potential participant's dementia.
* For the randomized stage only-has a history of prior TMS treatment (not TMS naïve)
* Currently enrolled in an interventional memory-enhancement study
* Alteration in cognitive-enhancement medication (or other treatment) dose within the past 2 months or active plans for dose alteration during the course of the study (previously unplanned changes that occur during the study will be examined on a case-by-case basis)
* Has started treatment with lecanemab, donanemab, or any other monoclonal antibody for Alzheimer's Disease within the past 6 months OR has a history of treatment complicated by amyloid-related imaging abnormalities (ARIA)
* Currently or within the past 2 weeks taking any of the following classes of medication:

  * Anticholinergic (e.g., tolterodine, benztropine)
  * Sedating antihistamines (e.g., diphenhydramine)
  * any drug that has significant anticholinergic or antihistaminic side effects (e.g., tricyclic antidepressant medications, mirtazapine).
  * Benzodiazepines. While not a strict rule out, this will be decided on a case-by-case basis
  * Opioid. While not a strict rule out, this will be decided on a case-by-case basis
  * Antiepileptic agents. While not a strict rule out, this will be decided on a case-by-case basis
  * Antipsychotic agents. While not a strict rule out, this will be decided on a case-by-case basis