Vagus nerve stimulation in patients with Alzheimer's disease: Additional follow-up results of a pilot study through 1 year.

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.

Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer's disease: a pilot study.

BACKGROUND: Vagus nerve stimulation (VNS) is an established treatment method for therapy-refractory epilepsy and, in Europe, for treatment-resistant depression also. Clinical and experimental investigations have also shown positive effects of VNS on cognition in epilepsy and depression. The purpose of the present pilot study was to investigate the effect of VNS on cognition in patients with Alzheimer's disease. METHOD: All the included patients (N = 10) met the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria for the diagnosis of Alzheimer's disease. Before the implantation of the vagus stimulator (NeuroCybernetic Prosthesis), the patients underwent neuropsychological tests (e.g., Alzheimer's Disease Assessment Scale-cognitive subscale [ADAS-cog] and Mini-Mental State Examination [MMSE]), computerized tomography of the brain, medical/neurologic and psychological examinations (status evaluation), and lumbar puncture with investigation of the cerebrospinal fluid. The presence of depressive symptoms was rated using the Montgomery-Asberg Depression Rating Scale. The VNS was initiated 2 weeks after the implantation, and the patients were followed up with regular investigations and tests over 6 months. Response was defined as improvement or absence of impairment in ADAS-cog and MMSE scores after 3 and 6 months. RESULTS: After 3 months of treatment, 7 of 10 patients were responders according to the ADAS-cog (median improvement of 3.0 points), and 9 of 10 patients were responders according to the MMSE (median improvement of 1.5 points). After 6 months of treatment, 7 patients were responders on the ADAS-cog (median improvement of 2.5 points), and 7 patients were responders on the MMSE (median improvement of 2.5 points). VNS was well tolerated, and its side effects were mild and transient. CONCLUSION: The results of this open-label pilot study suggest a positive effect of VNS on cognition in patients with Alzheimer's disease. Further studies are warranted.