Table of Contents Author Guidelines Submit a Manuscript
Journal of Aging Research
Volume 2011 (2011), Article ID 951403, 11 pages
http://dx.doi.org/10.4061/2011/951403
Review Article

Insulin-Like Growth Factor I and the Pathogenesis of Delirium: A Review of Current Evidence

1Research and Academic Institute of Athens, 27 Themistokleous Street and Akadimias, 10677 Athens, Greece
2HSPR Department, Institute of Psychiatry, Kings College, Room HO.09, David Goldberg Building, de Crespigny Park, London SE5 8AP, UK
3Psychiatry Graduate Entry Medical School, University of Limerick, Castletroy, Limerick, Ireland
4Department of Psychiatry, Midwestern Regional Hospital, Dooradoyle, Limerick, Ireland

Received 15 March 2011; Revised 26 April 2011; Accepted 12 May 2011

Academic Editor: James M. Harper

Copyright © 2011 Dimitrios Adamis and David Meagher. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. American Psychiatric Association, Task Force on DSM-IV, DSM-IV: Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association, Washington, DC, USA, 4th edition, 1994.
  2. N. Siddiqi, A. O. House, and J. D. Holmes, “Occurrence and outcome of delirium in medical in-patients: a systematic literature review,” Age and Ageing, vol. 35, no. 4, pp. 350–364, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. M. Elie, F. Rousseau, M. Cole, F. Primeau, J. McCusker, and F. Bellavance, “Prevalence and detection of delirium in elderly emergency department patients,” Canadian Medical Association Journal, vol. 163, no. 8, pp. 977–981, 2000. View at Google Scholar · View at Scopus
  4. L. J. Young and J. George, “Do guidelines improve the process and outcomes of care in delirium?” Age and Ageing, vol. 32, no. 5, pp. 525–528, 2003. View at Publisher · View at Google Scholar · View at Scopus
  5. D. Meagher, “More attention, less confusion: time to lessen the burden of delirium,” International Review of Psychiatry, vol. 21, no. 1, pp. 1–3, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. P. Trzepacz, D. Meagher, and M. Leonard, “Delirium,” in Textbook of Psychosomatic Medicine, J. Levenson, Ed., American Psychiatric Press, Washington, DC, USA, 2010. View at Google Scholar
  7. Y. Gustafson, D. Berggren, B. Brannstrom et al., “Acute confusional states in elderly patients treated for femoral neck fracture,” Journal of the American Geriatrics Society, vol. 36, no. 6, pp. 525–530, 1988. View at Google Scholar · View at Scopus
  8. K. Rockwood, “Acute confusion in elderly medical patients,” Journal of the American Geriatrics Society, vol. 37, no. 2, pp. 150–154, 1989. View at Google Scholar · View at Scopus
  9. S. E. Levkoff, D. A. Evans, B. Liptzin et al., “Delirium: the occurrence and persistence of symptoms among elderly hospitalized patients,” Archives of Internal Medicine, vol. 152, no. 2, pp. 334–340, 1992. View at Publisher · View at Google Scholar · View at Scopus
  10. J. D. Schor, S. E. Levkoff, L. A. Lipsitz et al., “Risk factors for delirium in hospitalized elderly,” Journal of the American Medical Association, vol. 267, no. 6, pp. 827–831, 1992. View at Publisher · View at Google Scholar · View at Scopus
  11. M. Elie, M. G. Cole, F. J. Primeau, and F. Bellavance, “Delirium risk factors in elderly hospitalized patients,” Journal of General Internal Medicine, vol. 13, no. 3, pp. 204–212, 1998. View at Publisher · View at Google Scholar · View at Scopus
  12. A. Hofman, W. A. Rocca, C. Brayne et al., “The prevalence of dementia in Europe: a collaborative study of 1980–1990 findings,” International Journal of Epidemiology, vol. 20, no. 3, pp. 736–748, 1991. View at Google Scholar
  13. D. M. Fick, J. V. Agostini, and S. K. Inouye, “Delirium superimposed on dementia: a systematic review,” Journal of the American Geriatrics Society, vol. 50, no. 10, pp. 1723–1732, 2002. View at Publisher · View at Google Scholar · View at Scopus
  14. L. Ansaloni, F. Catena, R. Chattat et al., “Risk factors and incidence of postoperative delirium in elderly patients after elective and emergency surgery,” British Journal of Surgery, vol. 97, no. 2, pp. 273–280, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. A. Chrispal, K. Prasad Mathews, and V. Surekha, “The clinical profile and association of delirium in geriatric patients with hip fractures in a tertiary care hospital in India,” Journal of Association of Physicians of India, vol. 58, no. 1, pp. 15–19, 2010. View at Google Scholar · View at Scopus
  16. J. G. Franco, C. Valencia, C. Bernal et al., “Relationship between cognitive status at admission and incident delirium in older medical inpatients,” Journal of Neuropsychiatry and Clinical Neurosciences, vol. 22, no. 3, pp. 329–337, 2010. View at Publisher · View at Google Scholar · View at PubMed
  17. D. B. Rolfson, J. E. McElhaney, G. S. Jhangri, and K. Rockwood, “Delirium: validity of the confusion assessment method in detecting postoperative delirium in the elderly,” International Psychogeriatrics, vol. 11, no. 4, pp. 431–438, 1999. View at Google Scholar · View at Scopus
  18. M. W. A. van Rijsbergen, A. W. Oldenbeuving, R. E. Nieuwenhuis-Mark et al., “Delirium in acute stroke: a predictor 7 of subsequent cognitive impairment? A two-year follow-up study,” Journal of the Neurological Sciences, vol. 306, no. 1-2, pp. 138–142, 2011. View at Publisher · View at Google Scholar · View at PubMed
  19. K. Alagiakrishnan and C. A. Wiens, “An approach to drug induced delirium in the elderly,” Postgraduate Medical Journal, vol. 80, no. 945, pp. 388–393, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. A. Clegg and J. B. Young, “Which medications to avoid in people at risk of delirium: a systematic review,” Age and Ageing, vol. 40, no. 1, pp. 23–29, 2011. View at Publisher · View at Google Scholar · View at PubMed
  21. A. M. J. MacLullich, A. Beaglehole, R. J. Hall, and D. J. Meagher, “Delirium and long-term cognitive impairment,” International Review of Psychiatry, vol. 21, no. 1, pp. 30–42, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. K. Rockwood, “The occurrence and duration of symptoms in elderly patients with delirium,” Journals of Gerontology, vol. 48, no. 4, pp. M162–M166, 1993. View at Google Scholar · View at Scopus
  23. J. McCusker, M. Cole, N. Dendukuri, L. Han, and E. Belzile, “The course of delirium in older medical inpatients: a prospective study,” Journal of General Internal Medicine, vol. 18, no. 9, pp. 696–704, 2003. View at Publisher · View at Google Scholar · View at Scopus
  24. D. Adamis, A. Treloar, F. C. Martin, and A. J. D. Macdonald, “Recovery and outcome of delirium in elderly medical inpatients,” Archives of Gerontology and Geriatrics, vol. 43, no. 2, pp. 289–298, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. J. C. Jackson, S. M. Gordon, R. P. Hart, R. O. Hopkins, and E. W. Ely, “The association between delirium and cognitive decline: a review of the empirical literature,” Neuropsychology Review, vol. 14, no. 2, pp. 87–98, 2004. View at Publisher · View at Google Scholar · View at Scopus
  26. M. A. Rudberg, P. Pompei, M. D. Foreman, R. E. Ross, and C. K. Cassel, “The natural history of delirium in older hospitalized patients: a syndrome of heterogeneity,” Age and Ageing, vol. 26, no. 3, pp. 169–174, 1997. View at Publisher · View at Google Scholar · View at Scopus
  27. A. J. D. Macdonald and A. Treloar, “Delirium and dementia; are they distinct?” Journal of the American Geriatrics Society, vol. 44, no. 8, pp. 1001–1002, 1996. View at Google Scholar · View at Scopus
  28. T. G. Fong, R. N. Jones, P. Shi et al., “Delirium accelerates cognitive decline in alzheimer disease,” Neurology, vol. 72, no. 18, pp. 1570–1575, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. D. J. Meagher, A. M. J. MacLullich, and J. V. Laurila, “Defining delirium for the International Classification of Diseases, 11th Revision,” Journal of Psychosomatic Research, vol. 65, no. 3, pp. 207–214, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. D. Adamis, A. Treloar, F. C. Martin, N. Gregson, G. Hamilton, and A. J. D. Macdonald, “APOE and cytokines as biological markers for recovery of prevalent delirium in elderly medical inpatients,” International Journal of Geriatric Psychiatry, vol. 22, no. 7, pp. 688–694, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. S. E. de Rooij, B. C. van Munster, J. C. Korevaar, and M. Levi, “Cytokines and acute phase response in delirium,” Journal of Psychosomatic Research, vol. 62, no. 5, pp. 521–525, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. A. M. J. MacLullich, K. J. Ferguson, T. Miller, S. E. J. A. de Rooij, and C. Cunningham, “Unravelling the pathophysiology of delirium: a focus on the role of aberrant stress responses,” Journal of Psychosomatic Research, vol. 65, no. 3, pp. 229–238, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. C. Alexia, G. Fallot, M. Lasfer, G. Schweizer-Groyer, and A. Groyer, “An evaluation of the role of insulin-like growth factors (IGF) and of type-I IGF receptor signalling in hepatocarcinogenesis and in the resistance of hepatocarcinoma cells against drug-induced apoptosis,” Biochemical Pharmacology, vol. 68, no. 6, pp. 1003–1015, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. B. R. Lackey, S. L. Gray, and D. M. Henricks, “Actions and interactions of the IGF system in Alzheimer's disease: review and hypotheses,” Growth Hormone and IGF Research, vol. 10, no. 1, pp. 1–13, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  35. I. Torres-Aleman, “Toward a comprehensive neurobiology of IGF-I,” Developmental Neurobiology, vol. 70, no. 5, pp. 384–396, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  36. C. P. Velloso, “Regulation of muscle mass by growth hormone and IGF-I,” British Journal of Pharmacology, vol. 154, no. 3, pp. 557–568, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. F. M. Yang, S. K. Inouye, M. A. Fearing, D. K. Kiely, E. R. Marcantonio, and R. N. Jones, “Participation in activity and risk for incident delirium,” Journal of the American Geriatrics Society, vol. 56, no. 8, pp. 1479–1484, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. H. D. Venters, S. R. Broussard, J. H. Zhou et al., “Tumor necrosis factorα and insulin-like growth factor-I in the brain: is the whole greater than the sum of its parts?” Journal of Neuroimmunology, vol. 119, no. 2, pp. 151–165, 2001. View at Publisher · View at Google Scholar · View at Scopus
  39. J. A. D'Ercole, P. Ye, and J. R. O'Kusky, “Mutant mouse models of insulin-like growth factor actions in the central nervous system,” Neuropeptides, vol. 36, no. 2-3, pp. 209–220, 2002. View at Publisher · View at Google Scholar · View at Scopus
  40. S. T. O'Keeffe and J. N. Lavan, “Predicting delirium in elderly patients: development and validation of a risk-stratification model,” Age and Ageing, vol. 25, no. 4, pp. 317–321, 1996. View at Publisher · View at Google Scholar · View at Scopus
  41. S. K. Inouye and P. A. Charpentier, “Precipitating factors for delirium in hospitalized elderly persons: predictive model and interrelationship with baseline vulnerability,” Journal of the American Medical Association, vol. 275, no. 11, pp. 852–857, 1996. View at Publisher · View at Google Scholar · View at Scopus
  42. S. Doré, S. Kar, and R. Quirion, “Insulin-like growth factor I protects and rescues hippocampal neurons against β-amyloid- and human amylin-induced toxicity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 9, pp. 4772–4777, 1997. View at Publisher · View at Google Scholar · View at Scopus
  43. P. J. Jenkens and S. A. Bustin, “Evidence for a link between IGF-I and cancer,” European Journal of Endocrinology, vol. 151, supplement 1, pp. S17–S22, 2004. View at Publisher · View at Google Scholar
  44. A. Meager, The Molecular Biology of Cytokines, John Wiley & Sons, Chichester, UK, 1998.
  45. F. De Benedetti, T. Alonzi, A. Moretta et al., “Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I: a model for stunted growth in children with chronic inflammation,” Journal of Clinical Investigation, vol. 99, no. 4, pp. 643–650, 1997. View at Google Scholar · View at Scopus
  46. B. R. Lackey, S. L. Gray, and D. M. Henricks, “Does the insulin-like growth factor system interact with prostaglandins and proinflammatory cytokines during neurodegeneration?” Experimental Biology and Medicine, vol. 224, no. 1, pp. 20–27, 2000. View at Google Scholar · View at Scopus
  47. C. H. Lang, L. Hong-Brown, and R. A. Frost, “Cytokine inhibition of JAK-STAT signaling: a new mechanism of growth hormone resistance,” Pediatric Nephrology, vol. 20, no. 3, pp. 306–312, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. L. J. Niedernhofer, G. A. Garinis, A. Raams et al., “A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis,” Nature, vol. 444, no. 7122, pp. 1038–1043, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. Y. Li, W. Xu, M. W. McBurney, and V. D. Longo, “SirT1 inhibition reduces IGF-I/IRS-2/Ras/ERK1/2 signaling and protects neurons,” Cell Metabolism, vol. 8, no. 1, pp. 38–48, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. D. Rudman, M. H. Kutner, and C. M. Rogers, “Impaired growth hormone secretion in the adult population: relation to age and adiposity,” Journal of Clinical Investigation, vol. 67, no. 5, pp. 1361–1369, 1981. View at Google Scholar
  51. D. R. Clemmons and J. J. Van Wyk, “Factors controlling blood concentration of somatomedin C,” Clinics in Endocrinology and Metabolism, vol. 13, no. 1, pp. 113–143, 1984. View at Google Scholar · View at Scopus
  52. K. Landin-Wilhelmsen, L. Wilhelmsen, G. Lappas et al., “Serum insulin-like growth factor I in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin,” Clinical Endocrinology, vol. 41, no. 3, pp. 351–357, 1994. View at Google Scholar
  53. S. Boonen, E. Lesaffre, J. Dequeker et al., “Relationship between baseline insulin-like growth factor-I (IGF-I) and femoral bone density in women aged over 70 years: potential implications for the prevention of age-related bone loss,” Journal of the American Geriatrics Society, vol. 44, no. 11, pp. 1301–1306, 1996. View at Google Scholar · View at Scopus
  54. J. A. M. J. L. Janssen, R. P. Stolk, H. A. P. Pols, D. E. Grobbee, F. H. De Jong, and S. W. J. Lamberts, “Serum free IGF-I, total IGF-I, IGFBP-1 and IGFBP-3 levels in an elderly population: relation to age and sex steroid levels,” Clinical Endocrinology, vol. 48, no. 4, pp. 471–478, 1998. View at Publisher · View at Google Scholar · View at Scopus
  55. A. Juul, K. Main, W. F. Blum, J. Lindholm, M. B. Ranke, and N. E. Skakkebaek, “The ratio between serum levels of insulin-like growth factor (IGF)-I and the IGF binding proteins (IGFBP-1, 2 and 3) decreases with age in healthy adults and is increased in acromegalic patients,” Clinical Endocrinology, vol. 41, no. 1, pp. 85–93, 1994. View at Google Scholar
  56. G. Paolisso, S. Ammendola, A. Del Buono et al., “Serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function,” Journal of Clinical Endocrinology and Metabolism, vol. 82, no. 7, pp. 2204–2209, 1997. View at Publisher · View at Google Scholar · View at Scopus
  57. Y. Arai, N. Hirose, K. Yamamura et al., “Serum insulin-like growth factor-1 in centenarians: implications of IGF-1 as a rapid turnover protein,” Journals of Gerontology A, vol. 56, no. 2, pp. M79–M82, 2001. View at Google Scholar · View at Scopus
  58. F. C. Martin, “Growth hormone, aging and frailty,” Reviews in Clinical Gerontology, vol. 9, no. 3, pp. 207–214, 1999. View at Publisher · View at Google Scholar · View at Scopus
  59. J. L. Thompson, G. E. Butterfield, R. Marcus et al., “The effects of recombinant human insulin-like growth factor-I and growth hormone on body composition in elderly women,” Journal of Clinical Endocrinology and Metabolism, vol. 80, no. 6, pp. 1845–1852, 1995. View at Google Scholar · View at Scopus
  60. K. C. Copeland, R. B. Colletti, J. T. Devlin, and T. L. McAuliffe, “The relationship between insulin-like growth factor-I, adiposity, and aging,” Metabolism, vol. 39, no. 6, pp. 584–587, 1990. View at Publisher · View at Google Scholar · View at Scopus
  61. T. B. Harris, D. Kiel, R. Roubenoff et al., “Association of insulin-like growth factor-I with body composition, weight history, and past health behaviors in the very old: the Framingham Heart Study,” Journal of the American Geriatrics Society, vol. 45, no. 2, pp. 133–139, 1997. View at Google Scholar · View at Scopus
  62. A. R. Cappola, K. Bandeen-Roche, G. S. Wand, S. Volpato, and L. P. Fried, “Association of IGF-I levels with muscle strength and mobility in older women,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 9, pp. 4139–4146, 2001. View at Publisher · View at Google Scholar · View at Scopus
  63. A. R. Cappola, Q. L. Xue, L. Ferrucci, J. M. Guralnik, S. Volpato, and L. P. Fried, “Insulin-like growth factor I and interleukin-6 contribute synergistically to disability and mortality in older women,” Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 5, pp. 2019–2025, 2003. View at Publisher · View at Google Scholar · View at Scopus
  64. R. Roubenoff, H. Parise, H. A. Payette et al., “Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study,” American Journal of Medicine, vol. 115, no. 6, pp. 429–435, 2003. View at Publisher · View at Google Scholar · View at Scopus
  65. M. Andreassen, I. Raymond, C. Kistorp, P. Hildebrandt, J. Eaber, and L. Ø. Kristensen, “IGF1 as predictor of all cause mortality and cardiovascular disease in an elderly population,” European Journal of Endocrinology, vol. 160, no. 1, pp. 25–31, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  66. G. A. Laughlin, E. Barrett-Connor, M. H. Criqui, and D. Kritz-Silverstein, “The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: the Rancho Bernardo study,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 1, pp. 114–120, 2004. View at Publisher · View at Google Scholar · View at Scopus
  67. S. Saydah, B. Graubard, R. Ballard-Barbash, and D. Berrigan, “Insulin-like growth factors and subsequent risk of mortality in the United States,” American Journal of Epidemiology, vol. 166, no. 5, pp. 518–526, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  68. K. A. Woods, C. Camacho-Hübner, M. O. Savage, and A. J. L. Clark, “Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene,” New England Journal of Medicine, vol. 335, no. 18, pp. 1363–1367, 1996. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  69. C. M. Cheng, R. R. Reinhardt, W. H. Lee, G. Joncas, S. C. Patel, and C. A. Bondy, “Insulin-like growth factor 1 regulates developing brain glucose metabolism,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 18, pp. 10236–10241, 2000. View at Google Scholar · View at Scopus
  70. K. D. Beck, L. Powell-Braxton, H. R. Widmer, J. Valverde, and F. Hefti, “Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons,” Neuron, vol. 14, no. 4, pp. 717–730, 1995. View at Google Scholar · View at Scopus
  71. J. B. Deijen, H. De Boer, and E. A. Van Der Veen, “Cognitive changes during growth hormone replacement in adult men,” Psychoneuroendocrinology, vol. 23, no. 1, pp. 45–55, 1998. View at Publisher · View at Google Scholar · View at Scopus
  72. M. A. Papadakis, D. Grady, D. Black et al., “Growth hormone replacement in healthy older men improves body composition but not functional ability,” Annals of Internal Medicine, vol. 124, no. 8, pp. 708–716, 1996. View at Google Scholar · View at Scopus
  73. A. Aleman, W. R. De Vries, E. H. F. De Haan, H. J. J. Verhaar, M. M. Samson, and H. P. F. Koppeschaar, “Age-sensitive cognitive function, growth hormone and insulin-like growth factor 1 plasma levels in healthy older men,” Neuropsychobiology, vol. 41, no. 2, pp. 73–78, 2000. View at Google Scholar · View at Scopus
  74. A. Aleman, H. J. J. Verhaar, E. H. F. De Haan et al., “Insulin-like growth factor-I and cognitive function in healthy older men,” Journal of Clinical Endocrinology and Metabolism, vol. 84, no. 2, pp. 471–475, 1999. View at Publisher · View at Google Scholar · View at Scopus
  75. A. Mustafa, L. Lannfelt, L. Lilius, A. Islam, B. Winblad, and A. Adem, “Decreased plasma insulin-like growth factor-I level in familial Alzheimer's disease patients carrying the Swedish APP 670/671 mutation,” Dementia and Geriatric Cognitive Disorders, vol. 10, no. 6, pp. 446–451, 1999. View at Publisher · View at Google Scholar · View at Scopus
  76. G. Murialdo, A. Barreca, F. Nobili et al., “Relationships between cortisol, dehydroepiandrosterone sulphate and insulin-like growth factor-I system in dementia,” Journal of Endocrinological Investigation, vol. 24, no. 3, pp. 139–146, 2001. View at Google Scholar · View at Scopus
  77. V. R. Sara, K. Hall, and K. Enzell, “Somatomedins in aging and dementia disorders of the Alzheimer type,” Neurobiology of Aging, vol. 3, no. 2, pp. 117–120, 1982. View at Publisher · View at Google Scholar
  78. A. Tham, A. Nordberg, F. E. Grissom, C. Carlsson-Skwirut, M. Viitanen, and V. R. Sara, “Insulin-like growth factors and insulin-like growth factor binding proteins in cerebrospinal fluid and serum of patients with dementia of the Alzheimer type,” Journal of Neural Transmission Parkinson's Disease and Dementia Section, vol. 5, no. 3, pp. 165–176, 1993. View at Google Scholar · View at Scopus
  79. B. Nasmanl, T. Olsson, J. R. Seckl et al., “Abnormalities in adrenal androgens, but not of glucocorticoids, in early Alzheimer's disease,” Psychoneuroendocrinology, vol. 20, no. 1, pp. 83–94, 1995. View at Publisher · View at Google Scholar
  80. E. Carro, J. L. Trejo, T. Gomez-Isla, D. LeRoith, and I. Torres-Aleman, “Serum insulin-like growth factor I regulates brain amyloid-β levels,” Nature Medicine, vol. 8, no. 12, pp. 1390–1397, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  81. W. Q. Zhao, P. N. Lacor, H. Chen et al., “Insulin receptor dysfunction impairs cellular clearance of neurotoxic oligomeric Aβ,” Journal of Biological Chemistry, vol. 284, no. 28, pp. 18742–18753, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  82. S. Sharma, J. Prasanthi, E. Schommer, G. Feist, and O. Ghribi, “Hypercholesterolemia-induced Aβ accumulation in rabbit brain is associated with alteration in IGF-1 signaling,” Neurobiology of Disease, vol. 32, no. 3, pp. 426–432, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  83. S. Kar, D. Seto, S. Doré, U. K. Hanisch, and R. Quirion, “Insulin-like growth factors-I and -II differentially regulate endogenous acetylcholine release from the rat hippocampal formation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 25, pp. 14054–14059, 1997. View at Publisher · View at Google Scholar · View at Scopus
  84. M. A. I. Åberg, N. D. Åberg, H. Hedbäcker, J. Oscarsson, and P. S. Eriksson, “Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus,” Journal of Neuroscience, vol. 20, no. 8, pp. 2896–2903, 2000. View at Google Scholar · View at Scopus
  85. M. A. I. Åberg, N. D. Åberg, T. D. Palmer et al., “IGF-I has a direct proliferative effect in adult hippocampal progenitor cells,” Molecular and Cellular Neuroscience, vol. 24, no. 1, pp. 23–40, 2003. View at Publisher · View at Google Scholar · View at Scopus
  86. S. Doré, S. Bastianetto, S. Kar, and R. Quirion, “Protective and rescuing abilities of IGF-I and some putative free radical scavengers against β-amyloid-inducing toxicity in neurons,” Annals of the New York Academy of Sciences, vol. 890, pp. 356–364, 1999. View at Google Scholar · View at Scopus
  87. L. Gasparini and H. Xu, “Potential roles of insulin and IGF-1 in Alzheimer's disease,” Trends in Neurosciences, vol. 26, no. 8, pp. 404–406, 2003. View at Publisher · View at Google Scholar · View at Scopus
  88. E. Giovannucci, “Nutrition, insulin, insulin-like growth factors and cancer,” Hormone and Metabolic Research, vol. 35, no. 11-12, pp. 694–704, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  89. W. M. Zawada, D. L. Kirschman, J. J. Cohen, K. A. Heidenreich, and C. R. Freed, “Growth factors rescue embryonic dopamine neurons from programmed cell death,” Experimental Neurology, vol. 140, no. 1, pp. 60–67, 1996. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  90. W. M. Zawada, D. J. Zastrow, E. D. Clarkson, F. S. Adams, K. P. Bell, and C. R. Freed, “Growth factors improve immediate survival of embryonic dopamine neurons after transplantation into rats,” Brain Research, vol. 786, no. 1-2, pp. 96–103, 1998. View at Publisher · View at Google Scholar · View at Scopus
  91. J. Guan, R. Krishnamurthi, H. J. Waldvogel, R. L. M. Faull, R. Clark, and P. Gluckman, “N-terminal tripeptide of IGF-1 (GPE) prevents the loss of TH positive neurons after 6-OHDA induced nigral lesion in rats,” Brain Research, vol. 859, no. 2, pp. 286–292, 2000. View at Publisher · View at Google Scholar · View at Scopus
  92. R. Krishnamurthi, S. Stott, M. Maingay et al., “N-terminal tripeptide of IGF-I improves functional deficits after 6-OHDA lesion in rats,” NeuroReport, vol. 15, no. 10, pp. 1601–1604, 2004. View at Publisher · View at Google Scholar · View at Scopus
  93. P. T. Trzepacz, “The neuropathogenesis of delirium: a need to focus our research,” Psychosomatics, vol. 35, no. 4, pp. 374–391, 1994. View at Google Scholar · View at Scopus
  94. P. T. Trzepacz, “Update on the neuropathogenesis of delirium,” Dementia and Geriatric Cognitive Disorders, vol. 10, no. 5, pp. 330–334, 1999. View at Publisher · View at Google Scholar · View at Scopus
  95. C. Murray, D. J. Sanderson, C. Barkus et al., “Systemic inflammation induces acute working memory deficits in the primed brain: relevance for delirium,” Neurobiology of Aging. In press. View at Publisher · View at Google Scholar · View at PubMed
  96. K. Wilson, C. Broadhurst, M. Diver, M. Jackson, and P. Mottram, “Plasma insulin growth factor-1 and incident delirium in older people,” International Journal of Geriatric Psychiatry, vol. 20, no. 2, pp. 154–159, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  97. A. W. Lemstra, K. J. Kalisvaart, R. Vreeswijk, W. A. van Gool, and P. Eikelenboom, “Pre-operative inflammatory markers and the risk of postoperative delirium in elderly patients,” International Journal of Geriatric Psychiatry, vol. 23, no. 9, pp. 943–948, 2008. View at Publisher · View at Google Scholar · View at PubMed
  98. D. Adamis, M. Lunn, F. C. Martin et al., “Cytokines and IGF-I in delirious and non-delirious acutely ill older medical inpatients,” Age and Ageing, vol. 38, no. 3, pp. 326–332, 2009. View at Publisher · View at Google Scholar · View at PubMed
  99. A. Morandi, M. L. Gunther, P. P. Pandharipande et al., “Insulin-like growth factor-1 and delirium in critically ill mechanically ventilated patients: a preliminary investigation,” International Psychogeriatrics. In press. View at Publisher · View at Google Scholar · View at PubMed
  100. C. Charriaut-Marlangue and Y. Ben-Ari, “A cautionary note on the use of the TUNEL stain to determine apoptosis,” NeuroReport, vol. 7, no. 1, pp. 61–64, 1995. View at Google Scholar · View at Scopus
  101. P. D. Gluckman, J. Guan, C. Williams et al., “Asphyxial brain injury—the role of the IGF system,” Molecular and Cellular Endocrinology, vol. 140, no. 1-2, pp. 95–99, 1998. View at Publisher · View at Google Scholar · View at Scopus
  102. C. D. M. Filho and M. Holzenberger, “IGF receptors in the adult brain,” in IGFs: Local Repair and Survival Factors Throughout Life Span, D. Clemmons, I. C. A. F. Robinson, and Y. Christen, Eds., pp. 125–142, Springer, London, UK, 2010. View at Google Scholar
  103. F. Peruzzi, M. Prisco, M. Dews et al., “Multiple signaling pathways of the insulin-like growth factor 1 receptor in protection from apoptosis,” Molecular and Cellular Biology, vol. 19, no. 10, pp. 7203–7215, 1999. View at Google Scholar · View at Scopus
  104. M. Párrizas and D. LeRoith, “Insulin-like growth factor-1 inhibition of apoptosis is associated with increased expression of the bcl-xL gene product,” Endocrinology, vol. 138, no. 3, pp. 1355–1358, 1997. View at Publisher · View at Google Scholar · View at Scopus
  105. R. W. Matheny and M. L. Adamo, “PI3K p110 alpha and p110 beta have differential effects on Akt activation and protection against oxidative stress-induced apoptosis in myoblasts,” Cell Death and Differentiation, vol. 17, no. 4, pp. 677–688, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  106. E. Carro, J. L. Trejo, S. Fernandez, A. M. Fernandez, and I. Torres-Aleman, “Insulin-like growth factor-I and neuroprotection,” in The Somatotrophic Axis in Brain Function, F. Nyberg, Ed., Elsevier Academic Press, London, UK, 2006. View at Google Scholar
  107. R. Yirmiya and I. Goshen, “Immune modulation of learning, memory, neural plasticity and neurogenesis,” Brain, Behavior, and Immunity, vol. 25, no. 2, pp. 181–213, 2011. View at Publisher · View at Google Scholar · View at PubMed
  108. K. E. Saatman, P. C. Contreras, D. H. Smith et al., “Insulin-like growth factor-1 (IGF-1) improves both neurological motor and cognitive outcome following experimental brain injury,” Experimental Neurology, vol. 147, no. 2, pp. 418–427, 1997. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  109. L. S. Mathews, G. Norstedt, and R. D. Palmiter, “Regulation of insulin-like growth factor I gene expression by growth hormone,” Proceedings of the National Academy of Sciences of the United States of America, vol. 83, no. 24, pp. 9343–9347, 1986. View at Google Scholar · View at Scopus
  110. M. A. Hynes, J. J. Van Wijk, P. J. Brooks, A. J. D'Ercole, M. Jansen, and P. K. Lund, “Growth hormone dependence of somatomedin-C/insulin-like growth factor-I and insulin-like growth factor-II messenger ribonucleic acids,” Molecular Endocrinology, vol. 1, no. 3, pp. 233–242, 1987. View at Google Scholar · View at Scopus
  111. F. Lupu, J. D. Terwilliger, K. Lee, G. V. Segre, and A. Efstratiadis, “Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth,” Developmental Biology, vol. 229, no. 1, pp. 141–162, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  112. O. Khorram, “Use of growth hormone and growth hormone secretagogues in aging: help or harm,” Clinical Obstetrics and Gynecology, vol. 44, no. 4, pp. 893–901, 2001. View at Publisher · View at Google Scholar · View at Scopus
  113. A. L. Yeo, D. Levy, F. C. Martin et al., “Frailty and the biochemical effects of recombinant human growth hormone in women after surgery for hip fracture,” Growth Hormone and IGF Research, vol. 13, no. 6, pp. 361–370, 2003. View at Publisher · View at Google Scholar · View at Scopus
  114. A. Pearson, A. De Vries, S. D. Middleton et al., “Cerebrospinal fluid cortisol levels are higher in patients with delirium versus controls,” BMC Research Notes, vol. 3, Article ID 33, 2010. View at Publisher · View at Google Scholar · View at PubMed
  115. M. Adamo, H. Werner, W. Farnsworth, C. T. Roberts, M. Raizada, and D. LeRoith, “Dexamethasone reduces steady state insulin-like growth factor I messenger ribonucleic acid levels in rat neuronal and glial cells in primary culture,” Endocrinology, vol. 123, no. 5, pp. 2565–2570, 1988. View at Google Scholar · View at Scopus
  116. W. L. Lowe Jr., T. Meyer, C. W. Karpen, and L. R. Lorentzen, “Regulation of insulin-like growth factor I production in rat C6 glioma cells: possible role as an autocrine/paracrine growth factor,” Endocrinology, vol. 130, no. 5, pp. 2683–2691, 1992. View at Publisher · View at Google Scholar · View at Scopus
  117. C. B. Chan, M. C. Tse, and C. H. K. Cheng, “Regulation and mechanism of growth hormone and insulin-like growth factor-I biosynthesis and secretion,” in The Somatotrophic Axis in Brain Function, F. Nyberg, Ed., pp. 7–23, Elsevier Academic Press, London, UK, 2006. View at Google Scholar
  118. C. Broadhurst and K. Wilson, “Immunology of delirium: new opportunities for treatment and research,” British Journal of Psychiatry, vol. 179, pp. 288–289, 2001. View at Publisher · View at Google Scholar · View at Scopus
  119. O. Nozaki, C. Takagi, K. Takaoka, T. Takata, and M. Yoshida, “Psychiatric manifestations accompanying interferon therapy for patients with chronic hepatitis C: an overview of cases in Japan,” Psychiatry and Clinical Neurosciences, vol. 51, no. 4, pp. 175–180, 1997. View at Google Scholar · View at Scopus
  120. C. J. Auernhammer and C. J. Strasburger, “Effects of growth hormone and insulin-like growth factor I on the immune system,” European Journal of Endocrinology, vol. 133, no. 6, pp. 635–645, 1995. View at Google Scholar · View at Scopus
  121. V. Hwa, B. Little, E. M. Kofoed, and R. G. Rosenfeld, “Transcriptional regulation of insulin-like growth factor-I by interferon-gamma requires STAT-5b,” Journal of Biological Chemistry, vol. 279, no. 4, pp. 2728–2736, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  122. D. Adamis, F. C. Martin, A. Treloar, and A. J. D. Macdonald, “Capacity, consent, and selection bias in a study of delirium,” Journal of Medical Ethics, vol. 31, no. 3, pp. 137–143, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  123. K. B. Auerswald, P. A. Charpentier, and S. K. Inouye, “The informed consent process in older patients who developed delirium: a clinical epidemiologic study,” American Journal of Medicine, vol. 103, no. 5, pp. 410–418, 1997. View at Publisher · View at Google Scholar · View at Scopus
  124. J. Francis, “A half-century of delirium research: time to close the gap,” Journal of the American Geriatrics Society, vol. 43, no. 5, pp. 585–586, 1995. View at Google Scholar · View at Scopus
  125. D. Adamis, A. Treloar, F. C. Martin, and A. J. D. Macdonald, “Ethical research in delirium: arguments for including decisionally incapacitated subjects,” Science and Engineering Ethics, vol. 16, no. 1, pp. 169–174, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  126. H. P. Guler, J. Zapf, C. Schmid, and E. R. Froesch, “Insulin-like growth factors I and II in healthy man. Estimations of half-lives and production rates,” Acta Endocrinologica, vol. 121, no. 6, pp. 753–758, 1989. View at Google Scholar · View at Scopus
  127. A. L. Barkan, “Defining normalcy of the somatotropic axis: an attainable goal?” Pituitary, vol. 10, no. 2, pp. 135–139, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  128. H. J. Koponen, E. Leinonen, U. Lepola, and P. J. Riekkinen, “A long-term follow-up study of cerebrospinal fluid somatostatin in delirium,” Acta Psychiatrica Scandinavica, vol. 89, no. 5, pp. 329–334, 1994. View at Google Scholar · View at Scopus
  129. R. Ross, J. Miell, E. Freeman et al., “Critically ill patients have high basal growth hormone levels with attenuated oscillatory activity associated with low levels of insulin-like growth factor-I,” Clinical Endocrinology, vol. 35, no. 1, pp. 47–54, 1991. View at Google Scholar · View at Scopus
  130. P. Cohen, “Insulin-like growth factor binding protein-3: insulin-like growth factor independence comes of age,” Endocrinology, vol. 147, no. 5, pp. 2109–2111, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  131. R. C. Kaplan, A. P. McGinn, M. N. Pollak et al., “Total insulinlike growth factor 1 and insulinlike growth factor binding protein levels, functional status, and mortality in older adults,” Journal of the American Geriatrics Society, vol. 56, no. 4, pp. 652–660, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus