A Phase II Study of Fornix Deep Brain Stimulation in Mild Alzheimer's Disease

Department

neurology

Document Type

Article

Abstract

Background: Deep brain stimulation (DBS) is used to modulate the activity of dysfunctional brain circuits. The safety and efficacy of DBS in dementia is unknown. Objective: To assess DBS of memory circuits as a treatment for patients with mild Alzheimer's disease (AD). Methods: We evaluated active \"on\" versus sham \"off\" bilateral DBS directed at the fornix-a major fiber bundle in the brain's memory circuit-in a randomized, double-blind trial (ClinicalTrials.gov NCT01608061) in 42 patients with mild AD. We measured cognitive function and cerebral glucose metabolism up to 12 months post-implantation. Results: Surgery and electrical stimulation were safe and well tolerated. There were no significant differences in the primary cognitive outcomes (ADAS-Cog 13, CDR-SB) in the \"on\" versus \"off\" stimulation group at 12 months for the whole cohort. Patients receiving stimulation showed increased metabolism at 6 months but this was not significant at 12 months. On post-hoc analysis, there was a significant interaction between age and treatment outcome: in contrast to patients <65 years old (n = 12) whose results trended toward being worse with DBS ON versus OFF, in patients‰¥65 (n = 30) DBS-f ON treatment was associated with a trend toward both benefit on clinical outcomes and a greater increase in cerebral glucose metabolism. Conclusion: DBS for AD was safe and associated with increased cerebral glucose metabolism. There were no differences in cognitive outcomes for participants as a whole, but participants aged‰¥65 years may have derived benefit while there was possible worsening in patients below age 65 years with stimulation.

Medical Subject Headings

neurology

Publication Date

2016

Publication Title

Journal of Alzheimer's Disease

ISSN

1387-2877

Volume

54

Issue

2

First Page

777

Last Page

787

Digital Object Identifier (DOI)

10.3233/JAD-160017

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