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Vagus nerve stimulation in patients with Alzheimer ’s disease

Year 2015, Volume: 2 Issue: 5, 281 - 82, 27.07.2015

Abstract

Alzheimer’s disease (AD) is a devastating, progressive condition associated with memory and cognitive disturbances, mood swings and behavioral changes, and the quality of life reduction (1). AD is the most common cause of dementia in person older than 65 years, with 1 in 10 older than 65 years afflicted and half among those older than 85 years afflicted. More than 4.5 million persons are currently affected in the United States by AD, and is expected to nearly triple by the year 2050 in the absence of preventive treatments (2).

AD is pathologically characterized by the accumulation of amyloid plaques and tau-associated neurofibrillary tangles (3). Patients with AD have increased cerebrospinal fluid (CSF) levels of tau protein and decreased CSF levels of β-amyloid.

Although, patients with AD experience significant elevations in CSF tau levels, CSF tau levels have been shown to remain stable over extended periods of time (4). Several neurotransmitter systems are pathologically altered in AD. Cholinergic neurons in the nucleus basalis of Meynert degenerate early in the course of the disease.

These neurons provide wide spread projections to the association cortices, and loss of acetlycholine is the mechanistic basis for cholinesterase inhibition in AD treatment. Glutamatergic function also is disregulated in AD, with inhibition of the pathological stimulation of the NMDA receptor providing the scientific rationale for the mechanism of the noncompetitive glutamate antagonist, memantine.

In addition to the atrophy of the basal forebrain cholinergic system, marked neuronal loss occurs within the locus ceruleus and the raphe nucleus in AD (5). Significant reduction of norepinephrine in the temporal cortex occur in AD and correlates with the degree of cognitive impairment (6).

Disturbances in serotonin metabolism also have been reported in AD (7). The U.S. Food and Drug Administration (FDA) had approved 5 drugs (tacrine, donepezil, rivastigmine, and galantamine) for the treatment of AD (8).

None of these treatments have been shown to modify the disease process in patients with AD, but they provide benefit to the patient, family, and caregivers by slowing the patient’s progressive decline.

Vagus nerve stimulation (VNS) has been shown to activate the locus ceruleus (9) and to increase norepinephrine (10) output into the basolateral amygdala and hippocampus in animal models.

Activation of the raphe nucleus with VNS also has been recently demonstrated (11). Merill et al reported cognitive-enhancing effects of VNS during the first 6 months of treatment in a small pilot study of 10 patients with AD (12). Later, they published a follow-up report including additional 7 patients, with for at least 1 year for all 17 patients.

Vagus nerve stimulation method promising new powerful alternative approaches in some neurological disorders especially in the treatment of refractory epilepsy (13).

In this clinical research, 14 patients with Alzheimer’s disease who were treated with VNS were reviewed and the results were assed in the light of the literature. Only first and second phase of AD patients were included in the study. In total 14 AD patients (7 man and 7 women aged between 68 and 82 year old) participated in this study. Patients were followed up for one year.

As soon as each implant was activated (two weeks after the implantation) attention of patients dramatically were improved, progressively going better On the other hand, 3 patients, who had difficulty in speaking along AD, improved by the VNS their talk within 3 months.

According to our observed preliminary results, a new therapy potential is arising struggling against Alzheimer diseases

References

  • 1. Evans DA, Funkenstein HH, Albert MS, et al. Prevalence of Alzheimer’s disease in a community population of older persons: higher than previously reported. JAMA 1989;262:2551–2556
  • 2. Ernst RL, Hay JW. The US economic and social costs of Alzheimer’s disease revisited. Am J Public Health 1994;84:1261–1264
  • 3. Sunderland T, Linker G, Mirza N, et al. Decreased betaamyloid1–42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. JAMA 2003;289:2094–2103
  • 4. Sunderland T, Wolozin B, Galasko D, et al. Longitudinal stability of CSF tau levels in Alzheimer patients. Biol Psychiatry 1999;46:750–755
  • 5. Reisberg B, Doody R, Stoffler A, et al. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med 2003;348:1333–1341
  • 6. Matthews KL, Chen CP, Esiri MM, et al. Noradrenergic changes, aggressive behavior, and cognition in patients with dementia. Biol Psychiatry 2002;51:407–416
  • 7. Gottfries CG. Disturbance of the 5-hydroxytryptamine metabolism in brains from patients with Alzheimer’s dementia. J Neural Transm Suppl 1990;30:33–43
  • 8. Knapp MJ, Knopman DS, Solomon PR, et al. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer’s disease. The Tacrine Study Group. JAMA 1994;271:985–991
  • 9. Naritoku DK, Terry WJ, Helfert RH. Regional induction of fos immuno-reactivity in the brain by anticonvulsant stimulation of the vagus nerve. Epilepsy Res 1995;22:53– 62
  • 10. Hassert DL, Miyashita T, Williams CL. The effects of peripheral vagal nerve stimulation at a memorymodulating intensity on norepinephrine output in the basolateral amygdala. Behav Neurosci 2004;118:79–88
  • 11. Kling MA, Loyd D, Sansbury N, et al. Effects of shortterm VNS therapy on fos expression in rat brain nuclei. Presented at the 59th An-nual Scientific Convention of The Society of Biological Psychiatry; May 15–17, 2003; San Francisco, CA.
  • 12. Sjögren MJ, Hellstrom PT, Jonsson MA, et al. Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer’s disease: a pilot study. J Clin Psychiatry 2002;63:972–980
  • 13. Merrill CA, Jonsson MAG, Minthon L, Ejnell H, Silander HC, Blennow K, Karlsson M, Nordlund A, Rolstad S, Warkentin S, Menachem E, Sjögren MJC. Vagus Nerve Stimulation in Patients With Alzheimer’s Disease: Additional Follow-Up Results of a Pilot Study Through 1 Year. J Clin Psychiatry 2006; 67:1171–1178.
  • 14. Tulgar M, Bilgin S, Yildirim A. The Human Body's Own Language to be Considered for Safe and Effective Neurostimulation. Neurol Ther. 2012; 9;1:2-7

Vagus nerve stimulation in patients with Alzheimer’s disease

Year 2015, Volume: 2 Issue: 5, 281 - 82, 27.07.2015

Abstract

References

  • 1. Evans DA, Funkenstein HH, Albert MS, et al. Prevalence of Alzheimer’s disease in a community population of older persons: higher than previously reported. JAMA 1989;262:2551–2556
  • 2. Ernst RL, Hay JW. The US economic and social costs of Alzheimer’s disease revisited. Am J Public Health 1994;84:1261–1264
  • 3. Sunderland T, Linker G, Mirza N, et al. Decreased betaamyloid1–42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. JAMA 2003;289:2094–2103
  • 4. Sunderland T, Wolozin B, Galasko D, et al. Longitudinal stability of CSF tau levels in Alzheimer patients. Biol Psychiatry 1999;46:750–755
  • 5. Reisberg B, Doody R, Stoffler A, et al. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med 2003;348:1333–1341
  • 6. Matthews KL, Chen CP, Esiri MM, et al. Noradrenergic changes, aggressive behavior, and cognition in patients with dementia. Biol Psychiatry 2002;51:407–416
  • 7. Gottfries CG. Disturbance of the 5-hydroxytryptamine metabolism in brains from patients with Alzheimer’s dementia. J Neural Transm Suppl 1990;30:33–43
  • 8. Knapp MJ, Knopman DS, Solomon PR, et al. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer’s disease. The Tacrine Study Group. JAMA 1994;271:985–991
  • 9. Naritoku DK, Terry WJ, Helfert RH. Regional induction of fos immuno-reactivity in the brain by anticonvulsant stimulation of the vagus nerve. Epilepsy Res 1995;22:53– 62
  • 10. Hassert DL, Miyashita T, Williams CL. The effects of peripheral vagal nerve stimulation at a memorymodulating intensity on norepinephrine output in the basolateral amygdala. Behav Neurosci 2004;118:79–88
  • 11. Kling MA, Loyd D, Sansbury N, et al. Effects of shortterm VNS therapy on fos expression in rat brain nuclei. Presented at the 59th An-nual Scientific Convention of The Society of Biological Psychiatry; May 15–17, 2003; San Francisco, CA.
  • 12. Sjögren MJ, Hellstrom PT, Jonsson MA, et al. Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer’s disease: a pilot study. J Clin Psychiatry 2002;63:972–980
  • 13. Merrill CA, Jonsson MAG, Minthon L, Ejnell H, Silander HC, Blennow K, Karlsson M, Nordlund A, Rolstad S, Warkentin S, Menachem E, Sjögren MJC. Vagus Nerve Stimulation in Patients With Alzheimer’s Disease: Additional Follow-Up Results of a Pilot Study Through 1 Year. J Clin Psychiatry 2006; 67:1171–1178.
  • 14. Tulgar M, Bilgin S, Yildirim A. The Human Body's Own Language to be Considered for Safe and Effective Neurostimulation. Neurol Ther. 2012; 9;1:2-7
There are 14 citations in total.

Details

Primary Language English
Journal Section Letter to Editor
Authors

Metin Tulgar

Erol Ozan

Zafer Akan

Publication Date July 27, 2015
Published in Issue Year 2015 Volume: 2 Issue: 5

Cite

APA Tulgar, M., Ozan, E., & Akan, Z. (2015). Vagus nerve stimulation in patients with Alzheimer ’s disease. Medical Science and Discovery, 2(5), 281-82. https://doi.org/10.17546/msd.97661
AMA Tulgar M, Ozan E, Akan Z. Vagus nerve stimulation in patients with Alzheimer ’s disease. Med Sci Discov. July 2015;2(5):281-82. doi:10.17546/msd.97661
Chicago Tulgar, Metin, Erol Ozan, and Zafer Akan. “Vagus Nerve Stimulation in Patients With Alzheimer ’s Disease”. Medical Science and Discovery 2, no. 5 (July 2015): 281-82. https://doi.org/10.17546/msd.97661.
EndNote Tulgar M, Ozan E, Akan Z (July 1, 2015) Vagus nerve stimulation in patients with Alzheimer ’s disease. Medical Science and Discovery 2 5 281–82.
IEEE M. Tulgar, E. Ozan, and Z. Akan, “Vagus nerve stimulation in patients with Alzheimer ’s disease”, Med Sci Discov, vol. 2, no. 5, pp. 281–82, 2015, doi: 10.17546/msd.97661.
ISNAD Tulgar, Metin et al. “Vagus Nerve Stimulation in Patients With Alzheimer ’s Disease”. Medical Science and Discovery 2/5 (July 2015), 281-82. https://doi.org/10.17546/msd.97661.
JAMA Tulgar M, Ozan E, Akan Z. Vagus nerve stimulation in patients with Alzheimer ’s disease. Med Sci Discov. 2015;2:281–82.
MLA Tulgar, Metin et al. “Vagus Nerve Stimulation in Patients With Alzheimer ’s Disease”. Medical Science and Discovery, vol. 2, no. 5, 2015, pp. 281-82, doi:10.17546/msd.97661.
Vancouver Tulgar M, Ozan E, Akan Z. Vagus nerve stimulation in patients with Alzheimer ’s disease. Med Sci Discov. 2015;2(5):281-82.