The prevalence of Alzheimer's Disease (AD) is rising, but existing medications provide only modest control of cognitive decline and associated symptoms, and novel therapies are urgently needed. This randomized sham-controlled trial will determine if an innovative low-risk remotely-supervised transcranial Direct Current Stimulation (tDCS) applied over the area of the dorsolateral prefrontal cortex for 30 minutes at the intensity of 2 mA five times per week for 6 months at home can improve cognitive performance and symptoms and modulate neuroimaging markers of neuroplasticity in 100 patients with mild to moderate AD. If effective, this novel intervention can substantially enhance AD symptom management at home, improve quality of life of AD patients and their families, and reduce burden associated with this debilitating illness.

The hallmark of Alzheimer's Disease (AD) is cognitive decline with varied associated symptoms and signs. Unfortunately, there is no cure as yet for AD. Available treatments, including 5 FDA-approved medications, have limited efficacy in terms of slowing pathological progression or controlling the symptoms and signs of cognitive decline in AD patients. Given the high burdens and costs of AD, and the therapeutic limitations, the development of novel treatment approaches for AD is of the highest importance for patients, families, medical providers, and society. This randomized controlled trial will determine if innovative, low-risk neurostimulation at home for 6 months can improve cognitive performance and symptoms in patients with mild to moderate AD.

The primary objective is to determine the effects produced by 6 months of active tDCS or sham delivered over dorsolateral prefrontal cortex (DLPFC) in home settings on global cognitive performance (assessed by ADAS-Cog test - primary outcome), and secondarily on executive control/spatial selective attention (Eriksen Flanker Test), depressed mood (Geriatric depression scale), quality of life (Quality of Life Questionnaire-Alzheimer's Disease), and patient satisfaction with both the device and procedure (Neurostimulation User's Survey), in mild-to-moderate AD patients (n=100). The investigators also aim to determine functional and structural brain connectivity/network changes in response to the study intervention using functional Magnetic Resonance Imaging (fMRI; during rest and during executive function tasks), diffusion-weighted imaging (DWI), and multivariate covariance-based analytic approaches. Lastly, the investigators aim to examine time characteristics (durability) of the tDCS behavioral and neuroplasticity effects for up to 3 months following the intervention period.

The intervention will consist of remotely supervised active tDCS stimulation and sham tDCS stimulation over the area of the dorsolateral prefrontal cortex, applied at home for 30 minutes 5 times per week for 6 months. Participants randomized to the active tDCS will receive at each application 30 minutes of direct current stimulation at the intensity of 2 mA. Participants randomized to the sham group will receive sham tDCS which consists of current ramped up to 2mA over 30 seconds, ramped down over 30 seconds and stay at 0 current for the remaining time of the 30-minute application.

Inclusion Criteria:

1. Community-dwelling male or female of age 60 and older
2. AD diagnosed by neurologists or geriatricians at our dementia and geriatric clinical sites. Clinicians will review the medical records of all potential cases to ensure the patients meet established clinical criteria for AD, and also examine individuals as needed to further establish the diagnosis. Mild-to moderate stage AD as determined by study clinicians using the Clinical Dementia Rating Scale (CDR). The CDR is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to AD: Memory, Orientation, Judgment & Problem Solving, Community Affairs, Home & Hobbies, and Personal Care. The necessary information to make each rating is obtained through a semi-structured interview of the patient and a reliable informant (e.g., family member). A CDR score of 0.5 or 1 is rated as mild severity and a score of 2 is rated as moderate severity. The investigators selected mild to moderate AD patients as our target population as they are the most prevalent AD severity group referred to our clinics, increasing generalizability. This mild to moderate AD group is also most likely to be cared for in the community and at home, in contrast to more advanced or severe AD stages, which are more prevalent in institutional settings (and will be the focus of our future studies)
3. If on dementia medication regimen, the regimen is stable for at least 4 weeks prior to enrollment. The investigators will not restrict clinicians from starting, adjusting or stopping dementia medications over the intervention period in keeping with the pragmatic nature of our trial, but will account for medications in both groups in our analysis
4. Able to speak and understand English or Spanish at a level sufficient undergo the study procedures and testing protocols
5. Willing to complete an MRI (exclusions relevant to neuroimaging are described below)
6. Able to provide Informed Consent (or able to provide assent with a legal surrogate providing informed consent.)

Exclusion Criteria:

1. Unstable medical or major psychiatric illnesses or unstable treatments for medical or major psychiatric illnesses. Any medical or psychiatric diagnosis is permitted as long as it has been clinically stable for at least 3 months, reflected in part by stability of treatments for at least 3 months, and is expected on the basis of clinical judgment to be in a stable phase that will likely extend for 6 months
2. History of head trauma, seizures, brain surgery, stroke or cancer affecting head, metal implants in the head or neck, compromised integrity or sensitivity of the skin at or near locations where electrodes will be placed (e.g., eczema, severe rashes, blisters, open wounds, burn including sunburns, cuts or irritation)
3. Currently participating in another intervention study or using neurostimulation device
4. Exclusions specific to neuroimaging procedure: the presence of any surgically implanted metallic devices, such as aneurysm clips or pacemakers that would be a safety contraindication for MRI. Subjects with large amounts of dental or surgical hardware in the head and neck will be excluded because magnetic susceptibility effects will lead to severe image artifacts in these subjects' images. Due to the confined space of the MRI magnet, subjects with a known history of claustrophobia will also be excluded as will subjects with weight >350lbs or waist circumference >55 inches
5. Must not be currently receiving or have received (or completed) within the past 3 months any monoclonal antibody treatment for Alzheimer's