Affiliations: [a] Department of Neurosurgery, David Geffen School of Medicine, and Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA
| [b] Functional Neurosurgery Unit, Tel Aviv Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Correspondence:
[*]
Correspondence to: Itzhak Fried, MD, PhD, Professor, Department of Neurosurgery, UCLA, 300 Stein Plaza Dwy,
Ste. 562, Los Angeles, CA 90095, USA. Tel.: +1 310 825 8409; Fax: +1 310 825 9385;
E-mail: [email protected].
Abstract: Deep brain stimulation has been successfully used in treatment of motor symptoms of Parkinson’s disease and other movement disorders. In a recent multi-center prospectively randomized study, deep brain stimulation of the fornix was administered in order to ameliorate the cognitive symptoms and clinical course of Alzheimer’s disease (AD). The study points to the possibility of modest slowing of the cognitive decline in AD in a subset of patients older than 65, while at the same time highlights the risk of stimulation in exacerbation of this decline in younger patients. The logic of conducting large clinical trials in the face of limited scientific understanding of the pathophysiology of AD and response of affected brain regions to electrical stimulation, is discussed with emphasis on the need to conduct: (i) animal studies in AD models, using precise focused stimulation; (ii) studies in patients who are implanted with depth electrodes for established clinical reasons (i.e., patients with epilepsy or movement disorders); and (iii) smaller adaptive studies in AD patients with systematic alterations of therapeutic parameters such as stimulation protocol.
Keywords: Alzheimer’s disease, dementia, deep brain stimulation, fornix, hippocampus, entorhinal area
