Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 54, Issue 2, Pages 777-787Publisher
IOS PRESS
DOI: 10.3233/JAD-160017
Keywords
Alzheimer's disease; dementia; deep brain stimulation; fornix
Categories
Funding
- National Institute on Aging [R01AG042165]
- Federal Economic Development Agency for Southern Ontario
- National Institutes of Health
- Functional Neuromodulation Ltd.
- NATIONAL INSTITUTE ON AGING [P50AG005146, P30AG010124, R01AG042165] Funding Source: NIH RePORTER
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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.
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