Abstract | BACKGROUND: 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.
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Authors | Andres M Lozano, Lisa Fosdick, M Mallar Chakravarty, Jeannie-Marie Leoutsakos, Cynthia Munro, Esther Oh, Kristen E Drake, Christopher H Lyman, Paul B Rosenberg, William S Anderson, David F Tang-Wai, Jo Cara Pendergrass, Stephen Salloway, Wael F Asaad, Francisco A Ponce, Anna Burke, Marwan Sabbagh, David A Wolk, Gordon Baltuch, Michael S Okun, Kelly D Foote, Mary Pat McAndrews, Peter Giacobbe, Steven D Targum, Constantine G Lyketsos, Gwenn S Smith |
Journal | Journal of Alzheimer's disease : JAD
(J Alzheimers Dis)
Vol. 54
Issue 2
Pg. 777-87
(09 06 2016)
ISSN: 1875-8908 [Electronic] Netherlands |
PMID | 27567810
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
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Chemical References |
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Topics |
- Aged
- Alzheimer Disease
(diagnostic imaging, metabolism, therapy)
- Deep Brain Stimulation
(methods)
- Double-Blind Method
- Female
- Fornix, Brain
(diagnostic imaging, metabolism)
- Glucose
(metabolism)
- Humans
- Male
- Middle Aged
- Pilot Projects
- Positron-Emission Tomography
(methods)
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