65 years): in younger controls, significantly stronger inverse associations were observed between MTR peak-height and fasted glucose, AUCglucose, fasted insulin, AUCinsulin and HOMA-IR in gray matter; and for AUCglucose, fasted insulin and HOMA-IR in white matter (all P-interaction < 0.05). Although the strength of the associations tended to attenuate with age in the offspring group, the difference between age groups was not statistically significant. Thus, associations between impaired insulin action and reduced microstructural brain parenchymal tissue homogeneity were stronger in offspring compared to controls, and seemed to diminish with age. " />
Display options
Share it on

Front Aging Neurosci. 2015 May 28;7:92. doi: 10.3389/fnagi.2015.00092. eCollection 2015.

Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age.

Frontiers in aging neuroscience

Abimbola A Akintola, Annette van den Berg, Mark A van Buchem, Steffy W Jansen, Eline P Slagboom, Rudi G Westendorp, Jeroen van der Grond, Diana van Heemst

Affiliations

  1. Department of Gerontology and Geriatrics, Leiden University Medical Centre Leiden, Netherlands.
  2. Department of Radiology, Leiden University Medical Centre Leiden, Netherlands.
  3. Department of Radiology, Leiden University Medical Centre Leiden, Netherlands ; Netherlands Consortium for Healthy Ageing Leiden, Netherlands ; Leiden Institute for Brain and Cognition, Leiden University Leiden, Netherlands.
  4. Netherlands Consortium for Healthy Ageing Leiden, Netherlands ; Department of Molecular Epidemiology, Leiden University Medical Centre Leiden, Netherlands.
  5. Department of Gerontology and Geriatrics, Leiden University Medical Centre Leiden, Netherlands ; Department of Public Health, University of Copenhagen Copenhagen, Denmark.
  6. Department of Radiology, Leiden University Medical Centre Leiden, Netherlands ; Netherlands Consortium for Healthy Ageing Leiden, Netherlands.
  7. Department of Gerontology and Geriatrics, Leiden University Medical Centre Leiden, Netherlands ; Netherlands Consortium for Healthy Ageing Leiden, Netherlands.

PMID: 26074813 PMCID: PMC4446544 DOI: 10.3389/fnagi.2015.00092

Abstract

Impaired glucose metabolism and type 2 diabetes have been associated with cognitive decline, dementia, and with structural and functional brain features. However, it is unclear whether these associations differ in individuals that differ in familial longevity or age. Here, we investigated the association between parameters of glucose metabolism and microstructural brain integrity in offspring of long-lived families ("offspring") and controls; and age categories thereof. From the Leiden Longevity Study (LLS), 132 participants underwent an oral glucose tolerance test (OGTT) to assess glycemia [fasted glucose and glucose area-under-the-curve (AUC)], insulin resistance [fasted insulin, AUCinsulin, and homeostatic model assessment of insulin resistance (HOMA-IR)], and pancreatic Beta cell secretory capacity (insulinogenic index). 3 Tesla MRI and Magnetization Transfer (MT) imaging MT-ratio (MTR) peak-height was used to quantify differences in microstructural brain parenchymal tissue homogeneity that remain invisible on conventional MRI. Analyses were performed in offspring and age-matched controls, with and without stratification for age. In the full offspring group only, reduced MTR peak-height in gray and white matter was inversely associated with AUCinsulin, fasted insulin, HOMA-IR and insulinogenic-index (all p < 0.01). When dichotomized for age (≤65 years and >65 years): in younger controls, significantly stronger inverse associations were observed between MTR peak-height and fasted glucose, AUCglucose, fasted insulin, AUCinsulin and HOMA-IR in gray matter; and for AUCglucose, fasted insulin and HOMA-IR in white matter (all P-interaction < 0.05). Although the strength of the associations tended to attenuate with age in the offspring group, the difference between age groups was not statistically significant. Thus, associations between impaired insulin action and reduced microstructural brain parenchymal tissue homogeneity were stronger in offspring compared to controls, and seemed to diminish with age.

Keywords: Magnetic Resonance Imaging (MRI); Magnetization Transfer Imaging (MTI); age; brain; familial longevity; glucose; insulin

References

  1. Stroke. 2003 Feb;34(2):392-6 - PubMed
  2. BMJ. 2005 Jun 11;330(7504):1360 - PubMed
  3. Neuroimage. 2002 Oct;17(2):825-41 - PubMed
  4. Nat Med. 2012 Feb 19;18(3):388-95 - PubMed
  5. Int J Obes Relat Metab Disord. 2003 Feb;27(2):260-8 - PubMed
  6. J Clin Invest. 2013 Nov;123(11):4799-808 - PubMed
  7. Curr Diab Rep. 2014 Apr;14(4):476 - PubMed
  8. Nature. 2013 Nov 7;503(7474):59-66 - PubMed
  9. Biochim Biophys Acta. 2012 Mar;1822(3):333-9 - PubMed
  10. Neurology. 2007 Sep 4;69(10):979-85 - PubMed
  11. Neurobiol Dis. 2011 Nov;44(2):161-73 - PubMed
  12. J Clin Invest. 2004 Oct;114(7):908-16 - PubMed
  13. Lancet. 1997 Oct 18;350(9085):1119-23 - PubMed
  14. J Nutr Health Aging. 2006 Jul-Aug;10(4):293-5 - PubMed
  15. Neurotherapeutics. 2007 Jul;4(3):401-13 - PubMed
  16. PLoS One. 2013;8(3):e57962 - PubMed
  17. Neuroradiology. 1994;36(2):101-3 - PubMed
  18. Hypertension. 2005 Jul;46(1):200-4 - PubMed
  19. JAMA. 2004 Nov 10;292(18):2237-42 - PubMed
  20. Neuroimage. 1999 Apr;9(4):393-406 - PubMed
  21. IEEE Trans Med Imaging. 2001 Jan;20(1):45-57 - PubMed
  22. Psychoneuroendocrinology. 2003 Oct;28(7):916-31 - PubMed
  23. Stroke. 2013 Jan;44(1):9-14 - PubMed
  24. Pharm Res. 2013 Oct;30(10):2475-84 - PubMed
  25. Diabetologia. 2003 Dec;46(12):1604-10 - PubMed
  26. Aging Cell. 2011 Feb;10(1):114-21 - PubMed
  27. Curr Alzheimer Res. 2007 Apr;4(2):111-6 - PubMed
  28. Eur J Hum Genet. 2006 Jan;14(1):79-84 - PubMed
  29. J Alzheimers Dis. 2005 Feb;7(1):45-61 - PubMed
  30. Diabetes Care. 1997 May;20(5):792-5 - PubMed
  31. Neurology. 2006 Feb 28;66(4):535-9 - PubMed
  32. BMJ. 2001 Jun 16;322(7300):1447-51 - PubMed
  33. Diabetes Care. 2014 Feb;37(2):493-500 - PubMed
  34. Ann N Y Acad Sci. 1992 Dec 26;673:260-9 - PubMed
  35. J Am Geriatr Soc. 2009 Sep;57(9):1634-7 - PubMed
  36. J Am Geriatr Soc. 2010 Mar;58(3):564-9 - PubMed
  37. Neurology. 1999 Dec 10;53(9):1937-42 - PubMed
  38. AJNR Am J Neuroradiol. 2013 Feb;34(2):317-22 - PubMed
  39. Neurology. 2004 Oct 12;63(7):1187-92 - PubMed

Publication Types