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J Alzheimers Dis. 2016 Sep 6;54(2):777-87. doi: 10.3233/JAD-160017.

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

Author information

1
Departments of Medicine (Neurology), Surgery (Neurosurgery) Psychology and Psychiatry, University of Toronto, Toronto, ON, Canada.
2
Functional Neuromodulation Ltd, Minneapolis, MN, USA.
3
Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada; Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, QC, Canada.
4
Memory and Alzheimer's Treatment Center & Alzheimer's Disease Research Center, Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
5
Department of Medicine, Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
6
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
7
University Health Network Memory Clinic, University of Toronto, Division of Neurology, Toronto, ON, Canada.
8
Clintara LLC, Boston, MA, USA.
9
Department of Neurology, Butler Hospital and the Alpert Medical School of Brown University, Providence, RI, USA.
10
Department of Neurosurgery, Rhode Island Hospital and the Alpert Medical School of Brown University, Providence, RI, USA.
11
Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
12
Banner Alzheimer's Institute, Phoenix, AZ, USA.
13
Department of Neurology, University of Arizona College of Medicine, Phoenix, AZ, USA.
14
Penn Memory Center, Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
15
Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA.
16
Departments of Neurology and Neurosurgery, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA.

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.

KEYWORDS:

Keywords: Alzheimer’s disease; deep brain stimulation; dementia; fornix

PMID:
27567810
PMCID:
PMC5026133
DOI:
10.3233/JAD-160017
[Indexed for MEDLINE]
Free PMC Article

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