Novel Brain Stimulation Treatment for Neuropsychiatric Symptoms in Alzheimer's Disease

The goal of this pilot study is to test a combination of two non-invasive brain stimulation methods, called iTBS (intermittent theta burst stimulation) and tDCS (transcranial direct current stimulation), in people with Alzheimer's Disease (AD) and related dementias (ADRD). This study will also explore whether the combined treatment shows promise for reducing neuropsychiatric symptoms like mood swings, apathy, and agitation, and will evaluate the impact of the treatment on caregivers.

The main questions the study aims to answer are:

1. Is the combined brain stimulation treatment practical and well-tolerated?
2. Do preliminary results suggest that this treatment could help manage neuropsychiatric symptoms and support a larger study?

Participants will:

* Attend nine in-person visits over three months.
* Complete one week of in-clinic brain stimulation sessions (iTBS) followed by four weeks of daily at-home brain stimulation sessions (tDCS).
* Take part in brain scans, questionnaires, and brain activity tests before and after the treatment.

This pilot study is a first step to assess whether this combined treatment approach is practical and whether it has potential to improve symptoms, laying the groundwork for larger studies in the future.

This study is designed to explore a new way to manage behavioral and emotional symptoms in people with Alzheimer's Disease (AD) and related dementias (ADRD). Many people with these conditions experience mood swings, apathy, or agitation, which can be difficult to treat with current medications due to limited effectiveness and side effects. This research is testing whether two types of brain stimulation, called iTBS (intermittent theta burst stimulation) and tDCS (transcranial direct current stimulation), can be combined to provide a non-invasive and potentially effective treatment for these symptoms.

Brain stimulation is already used in other areas of medicine and involves applying gentle magnetic or electrical stimulation to the brain. iTBS uses short bursts of magnetic pulses, while tDCS uses a low electrical current. Both methods are painless, safe, and do not require surgery. This study is the first to look at combining these two techniques for people with AD/ADRD, based on findings from other research that suggest the combination might have stronger effects than either method alone.

Since this is a pilot study, the focus is on understanding whether the treatment process is practical for both patients and caregivers. This includes evaluating how easy it is for participants to attend the clinic sessions, whether caregivers can successfully administer the at-home treatments, and whether the overall process is manageable for families. In addition to these practical questions, researchers will also collect preliminary data to see if the treatment helps improve behavioral symptoms and measure any changes in the brain using scans and brain activity tests.

Participants will spend one week receiving treatments in a clinic and four weeks using a portable device for at-home sessions. Researchers will closely monitor participants throughout the study to ensure safety and will follow up to see if any improvements last after the treatment ends.

The study is an important step in understanding whether this new approach has potential to help people with AD/ADRD and whether it should be studied further in larger trials. It also aims to identify how to make the treatment process as smooth and effective as possible for patients and caregivers.

Eligibility Criteria:
Inclusion criteria

1. veteran between the ages of 60 to 85
2. clinical diagnosis of mild to moderate Alzheimer's disease or related dementia
3. clinically significant neuropsychiatric symptoms (NPS) evidenced by a score ≥ 2 in at least one domain of the Neuropsychiatric Inventory Questionnaire
4. mild to moderate cognitive impairment demonstrated by a Mini-Mental State Examination (MMSE) score of 15-23
5. have a caregiver who is able and willing to escort the patient to/from clinic visits, answer questionnaires, and assist in the implementation of treatment sessions at home
6. if taking psychotropic medications, demonstrate stability for at least 4 weeks of treatment

Exclusion Criteria:

1. any contraindication for MRI
2. any contraindication for iTBS/tDCS including but not limited to seizure disorder, severe cardiovascular disease, history of brain surgery, or stroke involving the cerebral cortex near area of stimulation
3. current alcohol or substance use disorder determined by QuickSCID (nicotine allowed; mild cannabis and alcohol use is allowed)
4. neuropsychiatric symptoms (NPS) that are severe enough to preclude the intervention from being delivered safely and effectively, particularly agitation or aggression.

6) any unstable coexisting medical condition that in the opinion of the principal investigator(s) interferes with the treatment protocol or increase the likelihood of adverse events.