Non‐Invasive Temporal Interference Hippocampal Stimulation in Early Alzheimer’s Disease

Abstract Background Large‐scale efforts to reverse or stop the progression of Alzheimer’s disease (AD) and associated cognitive decline have failed to produce viable treatment options, highlighting the need for new interventional strategies. A significant feature of AD is aberrant changes in brain network activity and dynamics, closely coupled with functional impairment and pathophysiology in deep brain structures, such as the hippocampus. In this study, we are investigating the effects of multi‐session, non‐invasive temporal interference (TI) electrical stimulation of the hippocampus in early‐stage AD patients. This follows our recent work where we demonstrated the efficacy of TI electrical stimulation to non‐invasively target and modulate activity in the hippocampus of healthy young adults and improve episodic memory performance. Method The study consists of transcranial TI stimulation of the hippocampus of 24 early‐stage AD patients daily, in 10 consecutive sessions. We assess the safety and tolerability of the stimulation via questionnaires, interviews and brain scans. Additionally, we explore effects on the pathophysiology and resting state brain dynamics, using a battery of brain imaging modalities: positron emission tomography (PET) of mitochondrial complex‐1, blood oxygen level‐dependent functional magnetic resonance imaging (BOLD fMRI), diffusion tensor imaging (DTI) and arterial spin labelling (ASL). Finally, we explore the effects on cognitive performance using a battery of neurocognitive assessments. Result Herein, we will report the outcome of the study’s interim analysis pertaining to safety, neuroimaging and behaviour modulation outcome measures. Conclusion Herein, we will report the conclusion of the study’s interim analysis pertaining to safety, neuroimaging and behaviour modulation outcome measures.