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

作者：Lozano Andres M^*; Fosdick Lisa; Chakravarty M Mallar; Leoutsakos Jeannie Marie; Munro Cynthia; Oh Esther; Drake Kristen E; Lyman Christopher H; Rosenberg Paul B; Anderson William S; Tang Wai David F; Pendergrass Jo Cara; Salloway Stephen; Asaad Wael F; Ponce Francisco A; Burke Anna; Sabbagh Marwan; Wolk David A; Baltuch Gordon; Okun Michael S; Foote Kelly D; McAndrews Mary Pat; Giacobbe Peter; Targum Steven D; Lyketsos Constantine G^*; Smith Gwenn S

来源：Journal of Alzheimer's Disease, 2016, 54(2): 777-787.

DOI：10.3233/JAD-160017

• Alzheimer's disease
• dementia
• deep brain stimulation
• fornix

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.

• 出版日期2016