Hostname: page-component-8448b6f56d-t5pn6 Total loading time: 0 Render date: 2024-04-24T09:27:08.969Z Has data issue: false hasContentIssue false
  • English
  • Français

Acetylcholinesterase inhibition and insulin resistance in late onset Alzheimer's disease

Published online by Cambridge University Press:  27 July 2009

Ahmet Turan Isik  and
Ergun Bozoglu
Ahmet Turan Isik*
Affiliation:
Gulhane School of Medicine, Department of Internal Medicine, Division of Geriatric Medicine, Ankara, Turkey
Ergun Bozoglu
Affiliation:
Gulhane School of Medicine, Department of Internal Medicine, Division of Geriatric Medicine, Ankara, Turkey
*
Correspondence should be addressed to: Associate Professor Ahmet Turan Isik, MD, GATA Geriatri BD, 06018 Etlik, Ankara, Turkey. Phone: +90-312-304 40 31; Fax: +90-312-304 31 03. Email: atisik@yahoo.com.
Get access Rights & Permissions [Opens in a new window]

Abstract

Background: Insulin resistance (IR) may play a role in most pathogenic processes that promote the development of late onset Alzheimer's disease (LOAD). This study was designed to evaluate whether galantamine influenced peripheral IR in LOAD.

Methods: Ninety-five consecutive elderly patients, 40 LOAD and 55 non-demented patients were evaluated. IR was calculated with HOMA and modified-HOMA. All the patients were evaluated through comprehensive geriatric assessments at baseline and at 6, 12 and 18 months.

Results: Over three 6-month periods of galantamine treatment, compared to the baseline values, there was a significant increase at 6 and 12 months in the MMSE and at 6 months in the IADL scores (t = 3.25, p = 0.002 and t = 2.69, p = 0.011 for MMSE; t = 2.03, p = 0.049; for IADL, respectively). Although, there was an improvement in MMSE and IADL scores of galantamine-treated patients, there was no significant change in IR indexes and correlation between IR indexes and cognitive status in both groups during the treatment period.

Conclusions: This study showed no relation between cognitive improvement and IR by galantamine therapy in AD. In conclusion, peripheral IR and central nervous system IR may be different, and galantamine itself may show its effects without affecting the insulin-signaling pathway.

Keywords

galantamineAlzheimer'sinsulin resistanceelderly
Type
Research Article
Information
International Psychogeriatrics , Volume 21 , Issue 6 , December 2009 , pp. 1127 - 1133
Copyright
Copyright © International Psychogeriatric Association 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bernstein, H. G. et al. (1999). Insulin-degrading enzyme in the Alzheimer's disease brain: prominent localization in neurons and senile plaques. Neuroscience Letters, 263, 161–164. doi:10.1016/S0304-3940(99)00135-4.CrossRefGoogle ScholarPubMed
Bigl, M., Beck, M., Bleyl, A. D., Bigl, V. and Eschrich, K. (2000). Altered phosphofructokinase mRNA levels but unchanged isoenzyme pattern in brains from patients with Alzheimer's disease. Molecular Brain Research, 76, 411–414. doi:10.1016/S0169-328X(00)00019-X.CrossRefGoogle ScholarPubMed
Bigl, M., Apelt, J., Eschrich, K. and Schliebs, R. (2003). Cortical glucose metabolism is altered in aged transgenic Tg2576 mice that demonstrate Alzheimer plaque pathology. Journal of Neural Transmission, 110, 77–94. doi: 10.1007/s00702-002-0772-X.CrossRefGoogle ScholarPubMed
Craft, S., Reger, M. A. and Baker, L. D. (2006). Insulin resistance in Alzheimer's disease: a novel therapeutic target. Alzheimer's Disease and Related Disorders Annual, 5, London, Taylor and Francis (pp. 111–133).Google Scholar
Cummings, J. L., Schneider, L., Tariot, P. N., Kershaw, P. R. and Yuan, W. (2004). Reduction of behavioral disturbances and caregiver distress by galantamine in patients with Alzheimer's disease. American Journal of Psychiatry, 161, 532–538.CrossRefGoogle ScholarPubMed
Das, U. N. (2007). Acetylcholinesterase and butyrylcholinesterase as possible markers of low-grade systemic inflammation. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 13, RA214–221.Google ScholarPubMed
Ezoulin, M. J., Ombetta, J. E., Dutertre-Catella, H., Warnet, J. M. and Massicot, F. (2008). Antioxidative properties of galantamine on neuronal damage induced by hydrogen peroxide in SK-N-SH cells. Neurotoxicology, 29, 270–277. doi:10.1016/j.neuro.2007.11.004.CrossRefGoogle ScholarPubMed
Ferrara, C. M. and Goldberg, A. P. (2001). Limited value of the homeostasis model assessment to predict insulin resistance in older men with impaired glucose tolerance. Diabetes Care, 24, 245–249. doi: 10.1210/jc.2005-1803.CrossRefGoogle ScholarPubMed
Frölich, L. et al. (1998). Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease. Journal of Neural Transmission, 105, 423–438. doi: 10.1007/s007020050068.CrossRefGoogle ScholarPubMed
Gasparini, L., Netzer, WJ., Greengard, P. and Xu, H. (2002). Does insulin dysfunction play a role in Alzheimer's disease? Trends in Pharmacological Sciences, 23, 288–293. doi:10.1016/S0165-6147(02)02037-0.CrossRefGoogle ScholarPubMed
Gokcel, A. et al. (2003). Detection of insulin resistance in Turkish adults: a hospital-based study. Diabetes, Obesity and Metabolism, 5, 126–130. doi: 10.1046/j.1463-1326.2003.00253.X.CrossRefGoogle ScholarPubMed
Ho, L. et al. (2004). Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer's disease. FASEB Journal, 18, 902–904. doi: 10.1096/fj.03-0978fje.CrossRefGoogle Scholar
Houstis, N., Rosen, E. D. and Lander, E. S. (2006). Reactive oxygen species have a causal role in multiple forms of insulin resistance, Nature, 440, 944–948. doi:10.1038/nature04634.CrossRefGoogle ScholarPubMed
Hoyer, S. (1998). Is sporadic Alzheimer disease the brain type of non-insulin dependent diabetes mellitus? A challenging hypothesis. Journal of Neural Transmission, 105, 415–422. doi: 10.1007/s007020050067.CrossRefGoogle ScholarPubMed
Hoyer, S. (2004). Glucose metabolism and insulin receptor signal transduction in Alzheimer disease. European Journal of Pharmacology, 490, 115–125. doi: 10.1016/j.ejphar.2004.02.049CrossRefGoogle ScholarPubMed
Isik, A. T. et al. (2007). Is there any relation between insulin resistance and cognitive function in the elderly? International Psychogeriatrics, 19, 745–756. doi: 10.1017/S1041610207005406.CrossRefGoogle ScholarPubMed
Isik, A. T., Celik, T., Bozoglu, E. and Doruk, H. (2009). Trospium and cognition in patients with late onset Alzheimer disease. Journal of Nutrition, Health and Aging. (In press).CrossRefGoogle Scholar
Leibson, C. L. et al. (1997). Risk of dementia among persons with diabetes mellitus: a population-based cohort study. American Journal of Epidemiology, 145, 301–308. doi:10.1111/j.1749-6632.1997.tb48496.X.CrossRefGoogle ScholarPubMed
Li, X., Zhou, Z. G., Qi, H. Y., Chen, X. Y. and Huang, G. (2004). Replacement of insulin by fasting C-peptide in modified homeostasis model assessment to evaluate insulin resistance and islet beta cell function. Journal of Central South University. Medical Sciences, 29, 419–423.Google ScholarPubMed
Mesulam, M. (2004). The cholinergic lesion of Alzheimer's disease: pivotal factor or side show? Learning and Memory, 11, 43–49. doi: 10.1101/lm.69204.CrossRefGoogle ScholarPubMed
Pilcher, H. (2006). Alzheimer's disease could be “type 3 diabetes”, Lancet Neurology, 5, 388–389. doi:10.1016/S1474-4422(06)70434-3CrossRefGoogle ScholarPubMed
Randel, E. W., Mathews, M. S., Zhang, H., Seraj, J. S. and Sun, G. (2005). Relationship between serum butyrylcholinesterase and the metabolic syndrome. Clinical Biochemistry, 38, 799–805. doi:10.1016/j.clinbiochem.2005.04.008.CrossRefGoogle Scholar
Reyes, A. E. et al. (2004). Acetylcholinesterase-Abeta complexes are more toxic than Abeta fibrils in rat hippocampus: effect on rat beta-amyloid aggregation, laminin expression, reactive astrocytosis, and neuronal cell loss. American Journal of Pathology, 164, 2163–2174.CrossRefGoogle ScholarPubMed
Samochocki, M. et al. (2000). Galantamine is an allosterically potentiating ligand of the human alpha4/beta2 nAChR. Acta Neurologica Scandinavica. 176, 68–73. doi: 10.1124/jpet.103.063586.CrossRefGoogle ScholarPubMed
Sharma, P. et al. (2006). Mining literature for a comprehensive pathway analysis: a case study for retrieval of homocysteine related genes for genetic and epigenetic studies. Lipids in Health and Disease. 5, 1. doi: 10.1186/1476-511X-5-1.CrossRefGoogle ScholarPubMed
Stolk, R. P. et al. (1997). Insulin and cognitive function in elderly population: the Rotterdam Study. Diabetes Care, 20, 792–795.CrossRefGoogle ScholarPubMed
Taubes, G. (2003). Neuroscience: insulin insults may spur Alzheimer's disease. Science, 301, 40–41. doi: 10.1126/science.301.5629.40.CrossRefGoogle ScholarPubMed
Terry, A. V. Jr and Buccafusco, J. J. (2003). The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: recent challenges and their implications for novel drug development. Journal of Pharmacology and Experimental Therapeutics, 306, 821–827. doi: 10.1124/jpet.102.041616.CrossRefGoogle ScholarPubMed
Watson, G. S. and Craft, S. (2003). The role of insulin resistance in the pathogenesis of Alzheimer's disease: implications for treatment. CNS Drugs, 17, 27–45.CrossRefGoogle ScholarPubMed
Wilkinson, D. G., Francis, P. T., Schwam, E. and Payne-Parrish, J. (2004). Cholinesterase inhibitors used in the treatment of Alzheimer's disease: the relationship between pharmacological effects and clinical efficacy. Drugs and Aging, 21, 453–478.CrossRefGoogle ScholarPubMed
Yaffe, K. et al. (2004). The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA, 292, 2237–2242. doi:10.1001/jama.292.18.2237.CrossRefGoogle ScholarPubMed