Deep Brain Stimulation for Alzheimer's Disease: Tackling Circuit Dysfunction

Objectives: Treatments for Alzheimer's disease are urgently needed given its enormous human and economic costs and disappointing results of clinical trials targeting the primary amyloid and tau pathology. On the other hand, deep brain stimulation (DBS) has demonstrated success in other neurological and psychiatric disorders leading to great interest in DBS as a treatment for Alzheimer's disease. Materials and Methods: We review the literature on 1) circuit dysfunction in Alzheimer's disease and 2) DBS for Alzheimer's disease. Human and animal studies are reviewed individually. Results: There is accumulating evidence of neural circuit dysfunction at the structural, functional, electrophysiological, and neurotransmitter level. Recent evidence from humans and animals indicate that DBS has the potential to restore circuit dysfunction in Alzheimer's disease, similarly to other movement and psychiatric disorders, and may even slow or reverse the underlying disease pathophysiology. Conclusions: DBS is an intriguing potential treatment for Alzheimer's disease, targeting circuit dysfunction as a novel therapeutic target. However, further exploration of the basic disease pathology and underlying mechanisms of DBS is necessary to better understand how circuit dysfunction can be restored. Additionally, robust clinical data in the form of ongoing phase III clinical trials are needed to validate the efficacy of DBS as a viable treatment.