Association between raised inflammatory markers and cognitive decline in elderly people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study.
OBJECTIVE
To determine whether circulating levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha are associated with cognitive ability and estimated lifetime cognitive decline in an elderly population with type 2 diabetes.


METHODS
A cross-sectional study of 1,066 men and women aged 60-75 years with type 2 diabetes and living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study), was performed. Seven cognitive tests were used to measure abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility. The results were used to derive a general intelligence factor (g). A vocabulary-based test was administered as an estimate of peak prior cognitive ability. Results on the cognitive tests were assessed for statistical association with inflammatory markers measured in a venous blood sample at the time of cognitive testing.


RESULTS
Higher IL-6 and TNF-alpha levels were associated with poorer age- and sex-adjusted scores on the majority of the individual cognitive tests. They were also associated with g using standardized regression coefficients -0.074 to -0.173 (P < 0.05). After adjusting for vocabulary, education level, cardiovascular dysfunction, duration of diabetes, and glycemic control, IL-6 remained associated with three of the cognitive tests and with g.


CONCLUSIONS
In this representative population of people with type 2 diabetes, elevated circulating levels of inflammatory markers were associated with poorer cognitive ability. IL-6 levels were also associated with estimated lifetime cognitive decline.
Marioni
Riccardo E
RE
Centre for Population Health Sciences, University of Edinburgh, Scotland, UK. r.e.marioni@sms.ed.ac.uk
Strachan
Mark W J
MW
Reynolds
Rebecca M
RM
Lowe
Gordon D O
GD
Mitchell
Rory J
RJ
Fowkes
F Gerry R
FG
Frier
Brian M
BM
Lee
Amanda J
AJ
Butcher
Isabella
I
Rumley
Ann
A
Murray
Gordon D
GD
Deary
Ian J
IJ
Price
Jackie F
JF
D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D003072:Cognition Disorders / Q000097:blood* / Q000453:epidemiology* / Q000276:immunology; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology* / Q000276:immunology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D012606:Scotland / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein