Inflammatory proteins in plasma and the risk of dementia: the rotterdam study.
BACKGROUND
Increased levels of inflammatory proteins have been found in the brains and plasma samples of patients with dementia. Whether the levels of inflammatory proteins in plasma samples are elevated before clinical onset of dementia is unclear.


OBJECTIVE
To determine whether high levels of inflammatory proteins in plasma samples are associated with an increased risk of dementia.


METHODS
A case-cohort study within the Rotterdam Study, a population-based prospective cohort study in the Netherlands.


METHODS
The source population comprises 6713 subjects who, at baseline (1990-1993), were free of dementia and underwent venipuncture. From these, we selected both a random subcohort of 727 subjects and 188 cases who had developed dementia at follow-up.


METHODS
The associations between plasma levels of alpha1-antichymotrypsin, C-reactive protein, interleukin 6, the soluble forms of intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 and the risk of dementia were examined using the Cox proportional hazards regression models.


RESULTS
High levels of alpha1-antichymotrypsin, interleukin 6, and, to a lesser extent, C-reactive protein were associated with an increased risk of dementia; rate ratios per standard deviation increase were 1.49 (95% confidence interval, 1.23-1.81), 1.28 (95% confidence interval, 1.06-1.55), and 1.12 (95% confidence interval, 0.99-1.25), respectively. Similar associations were observed for Alzheimer disease, whereas rate ratios of vascular dementia were higher for alpha1-antichymotrypsin and C-reactive protein. Soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were not associated with dementia.


CONCLUSIONS
Plasma levels of inflammatory proteins are increased before clinical onset of dementia, Alzheimer disease, and vascular dementia.
Engelhart
Marianne J
MJ
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Geerlings
Mirjam I
MI
Meijer
John
J
Kiliaan
Amanda
A
Ruitenberg
Annemieke
A
van Swieten
John C
JC
Stijnen
Theo
T
Hofman
Albert
A
Witteman
Jacqueline C M
JC
Breteler
Monique M B
MM
D000368:Aged; D001798:Blood Proteins / Q000032:analysis*; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood; D015331:Cohort Studies; D003704:Dementia / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D000514:alpha 1-Antichymotrypsin / Q000097:blood
D001798:Blood Proteins; D015815:Cell Adhesion Molecules; D019010:Vascular Cell Adhesion Molecule-1; D000514:alpha 1-Antichymotrypsin; D002097:C-Reactive Protein