Structural brain changes and all-cause mortality in the elderly population-the mediating role of inflammation.

Publisher: Springer Country of Publication: Netherlands NLM ID: 101250497 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1574-4647 (Electronic) Linking ISSN: 01619152 NLM ISO Abbreviation: Age (Dordr) Subsets: MEDLINE

Original Publication: Dordrecht, The Netherlands ; Hingham, MA : Springer, c2005-

Cause of Death*; Aging/*pathology ; Brain/*ultrastructure ; Cerebral Small Vessel Diseases/*pathology ; Encephalitis/*pathology; Aged ; Aged, 80 and over ; Atrophy/pathology ; Biomarkers/blood ; C-Reactive Protein/analysis ; Cytokines/blood ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Prognosis ; Risk Factors ; Time Factors

While MRI brain changes have been related to mortality during ageing, the role of inflammation in this relationship remains poorly understood. Hence, this study aimed to investigate the impact of MRI changes on all-cause mortality and the mediating role of cytokines. All-cause mortality was evaluated in 268 community dwelling elderly (age 65-83 years) in the MEMO study (Memory and Morbidity in Augsburg elderly). MRI markers of brain atrophy and cerebral small vessel disease (SVD), C-reactive protein (CRP) and a panel of cytokines in serum were assessed. Cox proportional hazard models were used to estimate the association of MRI changes with survival over 9 years. Regression models were used to assess the hypothesis that inflammation is mediating the relationship between MRI-brain changes and mortality. In total, 77 (29 %) deaths occurred during a mean follow up of 9 years. After adjusting for confounders, the degree of global cortical atrophy and the level of the cytokines CRP, TNF-α and IL-8 were of higher significance in study participants who had died at follow-up in comparison to survivors. In Cox proportional hazard models, higher degrees of global cortical atrophy (HR 1.56, p = 0.003) and regional atrophy of the temporal lobe (HR 1.38, p = 0.011) were associated with a significantly increased risk of mortality. Mediation analyses revealed a partial mediation by IL-6 and IL-8 of the effects of global cortical atrophy on mortality. Global cortical brain atrophy is a significant indicator of survival in the elderly. Our study supports a possible role for inflammation in the atrophy pathogenesis. If replicated in other samples, IL-6 and IL-8 level assessment may improve risk prognosis for mortality.
Competing Interests: The authors declare that they have no conflict of interest. Source of funding The MEMO study is supported by the German Research Society (DFG, grant: BE1996/1–1). Data assessment was carried out within the framework of the Cooperative Health Research in the Augsburg Region (KORA). This study was supported by the Federal German Ministry of Education and Research (BMBF, grant 01ER1205). Dr. U. Hanning receives a research grant of the Medical Faculty of the University of Muenster.

J Geriatr Psychiatry Neurol. 2009 Mar;22(1):23-34. (PMID: 19196630)
N Engl J Med. 2003 Mar 27;348(13):1215-22. (PMID: 12660385)
Stroke. 1996 Feb;27(2):238-42. (PMID: 8571416)
Brain. 2003 Feb;126(Pt 2):424-32. (PMID: 12538408)
Psychol Methods. 2002 Dec;7(4):422-45. (PMID: 12530702)
Lancet Neurol. 2010 Jul;9(7):689-701. (PMID: 20610345)
Cell Mol Neurobiol. 2003 Oct;23(4-5):773-91. (PMID: 14514031)
Glia. 2003 Oct;44(1):1-12. (PMID: 12951652)
Neurology. 2000 Jan 11;54(1):90-4. (PMID: 10636131)
Neuroepidemiology. 2000 Sep-Oct;19(5):245-57. (PMID: 10965237)
J Neurol Neurosurg Psychiatry. 2001 Jan;70(1):9-14. (PMID: 11118240)
Age (Dordr). 2012 Oct;34(5):1295-308. (PMID: 21853262)
Neuroreport. 2000 Jun 5;11(8):1759-63. (PMID: 10852239)
Neurobiol Aging. 2009 Mar;30(3):450-6. (PMID: 17766013)
Immunology. 2010 Feb;129(2):154-69. (PMID: 20561356)
J Leukoc Biol. 2000 May;67(5):591-602. (PMID: 10810997)
Neurology. 2011 Mar 8;76(10 ):879-86. (PMID: 21383324)
Am J Med. 2006 Jun;119(6):519-25. (PMID: 16750966)
Age (Dordr). 2011 Jun;33(2):209-17. (PMID: 20617391)
Clin Exp Immunol. 2003 Apr;132(1):24-31. (PMID: 12653832)
Psychosom Med. 2005 May-Jun;67 Suppl 1:S6-9. (PMID: 15953804)
Age (Dordr). 2013 Apr;35(2):431-8. (PMID: 22170281)
Eur Neurol. 1998;39(2):80-9. (PMID: 9520068)
Neurology. 2014 Sep 9;83(11):967-73. (PMID: 25186857)
Neuroepidemiology. 2000 May-Jun;19(3):113-20. (PMID: 10705229)
Circulation. 2005 Aug 9;112(6):900-5. (PMID: 16061741)
Ageing Res Rev. 2010 Jan;9(1):41-50. (PMID: 19631766)
Acta Neurol Scand. 2016 Jan;133(1):68-74. (PMID: 25974422)
Age (Dordr). 2013 Dec;35(6):2215-27. (PMID: 23463321)
Neurology. 1998 Oct;51(4):986-93. (PMID: 9781518)
J Stroke Cerebrovasc Dis. 2006 Mar-Apr;15(2):57-63. (PMID: 17904049)
JAMA Neurol. 2013 Aug;70(8):1046-53. (PMID: 23753860)
Neurobiol Aging. 2007 Sep;28(9):1307-15. (PMID: 16857296)
Stroke. 2003 Mar;34(3):806-12. (PMID: 12624314)
BMC Neurol. 2005 Dec 02;5:23. (PMID: 16321166)
Eur Heart J. 1998 Aug;19(8):1197-207. (PMID: 9740341)
J Am Geriatr Soc. 2010 Apr;58(4):688-95. (PMID: 20398148)
Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1016-21. (PMID: 15706038)
Neurology. 2007 Mar 27;68(13):1032-8. (PMID: 17389308)
J Pers Soc Psychol. 1986 Dec;51(6):1173-82. (PMID: 3806354)
J Am Geriatr Soc. 2004 Jul;52(7):1045-50. (PMID: 15209640)
Immunol Allergy Clin North Am. 2003 Feb;23(1):15-39. (PMID: 12645876)
Age (Omaha). 1997 Jan;20(1):15-28. (PMID: 23604288)
Stroke. 2011 Nov;42(11):3105-9. (PMID: 21868739)
Age (Dordr). 2014 Apr;36(2):977-93. (PMID: 24402401)

Keywords: Brain ageing; Epidemiology; Mortality risking; Neuroimaging; Sex differences

0 (Biomarkers)
0 (Cytokines)
9007-41-4 (C-Reactive Protein)

Date Created: 20161022 Date Completed: 20171218 Latest Revision: 20181113

20231215

PMC5266221

10.1007/s11357-016-9951-9

27766478