Deep Brain Stimulation Targeting the Fornix for Mild Alzheimer Dementia (the ADvance Trial): A Two Year Follow-up Including Results of Delayed Activation.

TitleDeep Brain Stimulation Targeting the Fornix for Mild Alzheimer Dementia (the ADvance Trial): A Two Year Follow-up Including Results of Delayed Activation.
Publication TypeJournal Article
Year of Publication2018
AuthorsLeoutsakos J-MS, Yan H, Anderson WS, Asaad WF, Baltuch G, Burke A, M Chakravarty M, Drake KE, Foote KD, Fosdick L, Giacobbe P, Mari Z, McAndrews MPat, Munro CA, Oh ES, Okun MS, Pendergrass JCara, Ponce FA, Rosenberg PB, Sabbagh MN, Salloway S, Tang-Wai DF, Targum SD, Wolk D, Lozano AM, Smith GS, Lyketsos CG
JournalJ Alzheimers Dis
Volume64
Issue2
Pagination597-606
Date Published2018
ISSN1875-8908
Abstract

BACKGROUND: Given recent challenges in developing new treatments for Alzheimer dementia (AD), it is vital to explore alternate treatment targets, such as neuromodulation for circuit dysfunction. We previously reported an exploratory Phase IIb double-blind trial of deep brain stimulation targeting the fornix (DBS-f) in mild AD (the ADvance trial). We reported safety but no clinical benefits of DBS-f versus the delayed-on (sham) treatment in 42 participants after one year. However, secondary post hoc analyses of the one-year data suggested a possible DBS-f benefit for participants≥65 years.OBJECTIVE: To examine the long-term safety and clinical effects of sustained and delayed-on DBS-f treatment of mild AD after two years.METHODS: 42 participants underwent implantation of DBS-f electrodes, with half randomized to active DBS-f stimulation (early on) for two years and half to delayed-on (sham) stimulation after 1 year to provide 1 year of active DBS-f stimulation (delayed on). We evaluated safety and clinical outcomes over the two years of the trial.RESULTS: DBS-f had a favorable safety profile with similar rates of adverse events across both trial phases (years 1 and 2) and between treatment arms. There were no differences between treatment arms on any primary clinical outcomes. However, post-hoc age group analyses suggested a possible benefit among older (>65) participants.CONCLUSION: DBS-f was safe. Additional study of mechanisms of action and methods for titrating stimulation parameters will be needed to determine if DBS has potential as an AD treatment. Future efficacy studies should focus on patients over age 65.

DOI10.3233/JAD-180121
Alternate JournalJ. Alzheimers Dis.
PubMed ID29914028