Presentation Abstract

Program#/Poster#: 551.03/C38
Presentation Title: Deep brain stimulation for Alzheimer’s Disease is associated with structural changes in the human brain
Location: Hall A-C
Presentation time: Tuesday, Nov 15, 2011, 10:00 AM -11:00 AM
1Neurosurg., Toronto Western Hosp., Toronto, ON, Canada; 2Mouse Imaging Ctr. (MICe), The Hosp. for Sick Children, Toronto, ON, Canada; 3Rotman Res. Inst., Toronto, ON, Canada; 4Hosp. Universitario de Salamanca, Salamanca, Spain; 5Univ. Hosp. Germans Trias i Pujol, Badalona, Spain; 6Dept Neurosurg., Toronto Western Hosp. Rm 4-431 West, Toronto, ON, Canada
Abstract: Background: A phase I trial of deep brain stimulation (DBS) of the fornix in six patients with Alzheimer’s Disease (AD) (Laxton et al., Ann Neurol 2011) showed that DBS drove neural activity in the memory circuit, reversed hypometabolism in the temporal and parietal lobes, and possibly slowed cognitive decline. Based on these findings, we hypothesized that DBS might also be associated with structural changes in the brains of AD patients. Specifically, we predicted that DBS in AD patients might: 1) slow the process of hippocampal atrophy; and 2) preserve brain volumes in regions where hypometabolism had been reversed.
Methods: We analyzed 1.5T, T1-weighted, 3D MRI scans in six patients who had received DBS therapy for AD. Immediate post-surgical scans were compared with delayed scans taken following one year of chronic DBS therapy. Hippocampal volumes were measured by two independent, blinded observers using standard manual segmentation techniques. Deformation-based morphometry (DBM) was used to look for brain-wide voxel-by-voxel morphological changes between time points.
Results: Mean hippocampal volume was decreased by 2.8% at one year; this represented a significantly slower rate of atrophy compared to historical controls (approximately 5%/year). In two patients, clear hippocampal enlargement was observed, with volume expansions of 5.4% and 8.0% respectively. These two patients also demonstrated the best preservation of cognitive function at one year on the ADAS-Cog (Alzheimer’s Disease Assessment Scale-Cognitive Subscale). There was no significant difference in mean right and left hippocampal volume at either time point. An intra-class correlation coefficient of 0.93 (p<0.02) confirmed excellent inter-rater reliability between observers. DBM demonstrated statistically significant volume expansions in the posterior aspect of the superior temporal gyrus and rostral parietal regions, corresponding to areas of reversed hypometabolism.
Conclusions: Forniceal DBS for the treatment of AD appears to reduce or reverse hippocampal atrophy in certain patients, which could be related to preservation of cognitive function. Volume expansions distant from the site of stimulation are also seen. Further investigation is warranted to determine the underlying mechanisms and therapeutic implications of these findings.
Disclosures:   A.M. Lozano: Consultant/Advisory Board; St. Jude Medical, Inc., Medtronic, Inc.. Other; Intellectual property holder and licensor in the field of deep brain stimulation.
Keyword(s): ALZHEIMER'S
Support: Dana Foundation
Neurosurgery Research and Education Fund
Krembil Neuroscience Discovery Fund
[Authors]. [Abstract Title]. Program No. XXX.XX. 2011 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2011. Online.

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