Inflammatory markers and cognitive function in middle-aged adults: the Whitehall II study.
OBJECTIVE
To assess whether C-reactive protein (CRP) and interleukin-6 (IL-6) are associated with low cognitive performance and decline in middle-aged adults.


METHODS
The Whitehall II study; an ongoing large-scale, prospective occupational cohort study of employees from 20 London-based white-collar Civil Service departments.


METHODS
Data from more than 3000 males and 1200 female employees.


METHODS
Inflammatory makers measured in 1991-1993 and five cognitive tests (short-term verbal memory, inductive reasoning (AH4-I), vocabulary (Mill Hill), and phonemic and semantic fluency) performed in 1997-1999 and 2002-2004. Performance in the lowest sex-specific quintile indicated low cognitive performance or decline. Covariates included sociodemographics, health behaviours and health conditions.


RESULTS
In age-adjusted analyses both CRP and IL-6 were associated with all cognitive measures in 1997-1999, even though the association with memory was not consistent. After extensive adjustment raised CRP levels were only associated with poor cognitive performance on the AH4-I (OR=1.38; 95% CI: 1.05-1.82) and Mill Hill (OR=1.52; 95% CI: 1.14-2.03) and IL-6 on semantic fluency (OR=1.27; 95% CI: 1.14-2.03). Associations were more evident in men than in women. No clear relationship was observed for decline.


CONCLUSIONS
Our results suggest that raised levels of inflammatory markers in midlife are moderately associated with lower cognitive status, but little with cognitive decline.
Gimeno
David
D
International Institute for Society and Health, Department of Epidemiology and Public Health, UCL Medical School, London, UK. d.gimeno@ucl.ac.uk
Marmot
Michael G
MG
Singh-Manoux
Archana
A
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000523:psychology*; D015850:Interleukin-6 / Q000097:blood; D008019:Life Style; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012307:Risk Factors
D015415:Biomarkers; D015850:Interleukin-6; D002097:C-Reactive Protein
Int J Epidemiol. 2005 Apr;34(2):251-6
15576467
J Gerontol A Biol Sci Med Sci. 2004 Mar;59(3):268-74
15031312
Psychol Aging. 2001 Mar;16(1):3-11
11302365
Res Immunol. 1992 Jul-Aug;143(6):617-20
1455052
Neurology. 2003 Jul 8;61(1):76-80
12847160
Epidemiology. 2006 Mar;17(2):183-9
16477259
Neuropsychol Rev. 2006 Mar;16(1):17-42
16794878
J Epidemiol Community Health. 2005 Jun;59(6):495-501
15911646
J Clin Epidemiol. 2005 Dec;58(12):1308-15
16291476
Br J Haematol. 1999 Feb;104(2):246-57
10050704
J Neuroimmunol. 2003 Jan;134(1-2):142-50
12507782
J Neurol Neurosurg Psychiatry. 1994 Feb;57(2):202-7
8126506
Psychol Aging. 1995 Dec;10(4):578-89
8749585
Neurology. 2005 Oct 25;65(8):1218-26
16247048
Circulation. 2002 Dec 17;106(25):3143-421
12485966
Br J Psychol. 2003 Feb;94(Pt 1):63-71
12648389
Psychol Med. 2009 Mar;39(3):413-23
18533059
Lancet Neurol. 2005 Jun;4(6):371-80
15907742
Am J Epidemiol. 2008 Jan 1;167(1):112-20
17873099
J Psychiatr Res. 1975 Nov;12(3):189-98
1202204
Am J Alzheimers Dis Other Demen. 2006 Aug-Sep;21(4):258-62
16948290
Eur J Epidemiol. 2007;22(10):675-83
17668278
Physiol Behav. 2007 Sep 10;92(1-2):105-9
17644146
Am J Clin Pathol. 1994 Dec;102(6):802-5
7801895
Am J Epidemiol. 2005 Aug 1;162(3):267-78
15987729
Neurology. 2002 Aug 13;59(3):371-8
12177370
Clin Chem. 1997 Jan;43(1):52-8
8990222
N Engl J Med. 1999 Feb 11;340(6):448-54
9971870
Cognition. 2004 Oct;93(3):B109-21
15178381
Stroke. 1997 Apr;28(4):777-84
9099196
JAMA. 2004 Nov 10;292(18):2237-42
15536110
Clin Chem. 2001 Mar;47(3):444-50
11238295
Arterioscler Thromb Vasc Biol. 2006 Aug;26(8):1883-8
16728658
Arch Intern Med. 2008 Jun 9;168(11):1165-73
18541824
J Am Geriatr Soc. 2007 May;55(5):708-16
17493190
J Epidemiol Community Health. 2003 Feb;57(2):147-53
12540692
Occup Med (Lond). 1999 May;49(4):225-9
10474913
Cortex. 2007 Jul;43(5):607-15
17715796
J Am Geriatr Soc. 2007 May;55(5):700-7
17493189
J Gerontol A Biol Sci Med Sci. 2008 Jan;63(1):50-5
18245760
Arch Intern Med. 2004 Sep 27;164(17):1873-80
15451762
Neurology. 2005 Apr 26;64(8):1371-7
15851726
Lancet Neurol. 2006 Sep;5(9):735-41
16914401
Curr Opin Psychiatry. 2008 Jan;21(1):8-13
18281834
Neurobiol Aging. 2009 May;30(5):769-81
17913303
Br J Haematol. 2003 Jul;122(1):135-41
12823355
Arch Neurol. 2000 Feb;57(2):170-1
10681073
Circulation. 2004 Dec 21;110(25):e545-9
15611379