Vagus Nerve Stimulation in Patients With Alzheimer's Disease: Additional Follow-Up Results of a Pilot Study Through 1 Year

Charley A. Merrill, Ph.D.; Michael A. G. Jonsson, M.D.; Lennart Minthon, M.D., Ph.D.; Hasse Ejnell, M.D., Ph.D.; Hans C-son Silander, M.D., Ph.D.; Kaj Blennow, M.D., Ph.D.; Mats Karlsson, M.D.; Arto Nordlund, M.A.; Sindre Rolstad, M.A.; Siegbert Warkentin, Ph.D.; Elinor Ben-Menachem, M.D., Ph.D.; and Magnus J. C. Sjögren, M.D., Ph.D.

Background: Cognitive-enhancing effects of vagus nerve stimulation (VNS) have been reported during 6 months of treatment in a pilot study of patients with Alzheimer's disease (AD). Data through 1 year of VNS (collected from June 2000 to September 2003) are now reported.

Method: All patients (N = 17) met the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD. Responder rates for the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Mini-Mental State Examination (MMSE) were measured as improvement or absence of decline from baseline. Global change, depressive symptoms, and quality of life were also assessed. Cerebrospinal fluid (CSF) levels for total tau, tau phosphorylated at Thr181 (phosphotau), and Abeta42 were measured by standardized enzyme-linked immunosorbent assay (ELISA).

Results: VNS was well tolerated. After 1 year, 7 (41.2%) of 17 patients and 12 (70.6%) of 17 patients improved or did not decline from baseline on the ADAS-cog and MMSE, respectively. Twelve of 17 patients were rated as having no change or some improvement from baseline on the Clinician Interview-Based Impression of Change (CIBIC+). No significant decline in mood, behavior, or quality of life occurred during 1 year of treatment. The median change in CSF tau at 1 year was a reduction of 4.8% (p = .057), with a 5.0% increase in phosphotau (p = .040; N = 14).

Conclusion: The results of this study support long-term tolerability of VNS among patients with AD and warrant further investigation.

(J Clin Psychiatry 2006;67:1171-1178)

Received Nov. 10, 2005; accepted April 11, 2006. From the Forest Research Institute, Jersey City, N.J. (Dr. Merrill); the Institute of Clinical Neuroscience, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden (Drs. Jonsson, Blennow, and Ben-Menachem, Mr. Rolstad, and Mr. Nordlund); the Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden (Drs. Minthon, Karlsson, and Warkentin); the Sahlgren University Hospital, Göteborg, Sweden (Drs. Ejnell and Silander); and the Department of Neurotec, Karolinska Institute, Huddinge, Sweden and Organon, N.V., Oss, The Netherlands (Dr. Sjögren).

Supported by grants from Alzheimerfonden, Bohuslandstingets FoU fond, Cyberonics, Inc., Fredrik och Ingrid Thurings Stiftelse, Martina och Wilhelm Lundgrens Stiftelse, Stiftelsen för Gamla Tjänarinnor, Pfannenstills forskningsfond, the Swedish Research Council, and the Swedish Association of Neurologically Disabled.

Dr. Merrill is an employee of the Forest Research Institute and is a former employee of Cyberonics. Dr. Ben-Menachem is a consultant to, has received grant/research support and honoraria from, and has served on the speakers or advisory board for Cyberonics. Dr. Sjögren is an employee of Organon N.V. The other authors report no additional financial or other relationships relevant to the subject of this article.

The authors thank Christina Holmberg, R.N., for technical assistance; Stefan Hosten, M.A., of Cyberonics, Inc., manufacturer of the VNS therapy system, for project management; Stacey Arrambide, M.S., of Synergos, Inc., for statistical analysis; and Natasha Calder, M.A., of Cyberonics, Inc., for assistance with preparation of the manuscript.

Corresponding author and reprints: Magnus Sjögren, M.D., Ph.D., Karolinska Institutet, Department of Neurotec, KFC, Novum plan4 SE-141 86 Huddinge, Sweden (e-mail: magnus.sjogren@neurotec.ki.se).