Individual Closed-Loop Neuromodulation Therapy for Alzheimer's Disease

The project is a placebo-controlled study that aims to use closed-loop transcranial alternating current stimulation (tACS) to study patients with symptoms of mild cognitive impairment which is likely due to Alzheimer's disease or another form of dementia (AD-MCI). Patients will undergo an EEG and complete some questionnaires and computer tasks during each study visit. The project has the following aims and hypotheses: 1.) To determine the impact of closed-loop 40 Hz tACS on the entrainment of natural gamma rhythms in patients with AD-MCI, 2.) To determine the impact of closed-loop 40 Hz tACS on cognitive performance in patients with AD-MCI, and 3.) To assess the relationship between baseline neurodegenerative burden and impact of tACS. [exploratory]

you will receive one of four treatment conditions that include active and sham tACS. The four conditions are the following: (1) closed-loop-tACS (peak-locked), (2) closed-loop-tACS (trough-locked), (3) open-loop tACS, and (4) sham tACS. Although each subject will undergo all four treatments in four separate study visits, the order of the treatments will be randomized

Measured using Rey Auditory Verbal Learning Task (RAVLT) which is broken into 6 blocks with each block including a list of 15 words and higher word remembrance in each block indicates a better outcomes, and Face-Name Association Task (FNAT) task where a higher score of matching face to name (out of 60 trials) indicates a better outcome

Changes in gamma power on cognition in patients with AD-MCI including the effect of baseline neurodegenerative burden/biomarkers. [exploratory]

Measured using Rey Auditory Verbal Learning Task (RAVLT) which is broken into 6 blocks with each block including a list of 15 words and higher word remembrance in each block indicates a better outcomes, and Face-Name Association Task (FNAT) task where a higher score of matching face to name (out of 60 trials) indicates a better outcome, any MRI/PET scans provided prior to study involvement, and changes in gamma power using closed loop 40 Hertz tACS device

Inclusion Criteria: Overall cognitive functional status consistent with amnesic MCI (CDR 0.5) likely due to AD (AD biomarker supported) 50-80 years of age English native speakers Exclusion Criteria: Known presence of a structural brain lesion (e.g., tumor, cortical infarct) Acute or decompensated active medical conditions, including cancer, cardiovascular disease, stroke, congestive heart failure Active hematological, renal, pulmonary, endocrine or hepatic disorders Longstanding premorbid history (i.e., longer than 10 years) of alcohol or substance abuse with continuous abuse up to and including the time that the symptoms leading to clinical presentation developed tACS contraindications (lesions in the scalp, history of seizures)