http://repub.eur.nl/res/aut/4905/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/13377/ 2004-05-01T00:00:00Z 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. DESIGN AND SETTING: A case-cohort study within the Rotterdam Study, a population-based prospective cohort study in the Netherlands. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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. CONCLUSION: Plasma levels of inflammatory proteins are increased before clinical onset of dementia, Alzheimer disease, and vascular dementia. http://repub.eur.nl/res/pub/10022/ 2002-01-01T00:00:00Z OBJECTIVE: The associations of vitamin B(12), folate, and homocysteine with depression were examined in a population-based study. METHOD: The authors screened 3,884 elderly people for depressive symptoms. Subjects with positive screening results had psychiatric workups. Folate, vitamin B(12), and homocysteine blood levels were compared in 278 persons with depressive symptoms, including 112 with depressive disorders, and 416 randomly selected reference subjects. Adjustments were made for age, gender, cardiovascular disease, and functional disability. RESULTS: Hyperhomocysteinemia, vitamin B(12) deficiency, and to a lesser extent, folate deficiency were all related to depressive disorders. For folate deficiency and hyperhomocysteinemia, the association with depressive disorders was substantially reduced after adjustment for functional disability and cardiovascular disease, but for vitamin B(12) this appeared independent. CONCLUSIONS: The association of vitamin B(12) and folate with depressive disorders may have different underlying mechanisms. Vitamin B(12) may be causally related to depression, whereas the relation with folate is due to physical comorbidity. http://repub.eur.nl/res/pub/9899/ 2002-01-01T00:00:00Z Inflammatory mediators and soluble cell adhesion molecules predict cardiovascular events. It is not clear whether they reflect the severity of underlying atherosclerotic disease. Within the Rotterdam Study, we investigated the associations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 with noninvasive measures of atherosclerosis. Levels of CRP were assessed in a random sample of 1317 participants, and levels of IL-6 and soluble cell adhesion molecules were assessed in a subsample of 714 participants. In multivariate analyses, logarithmically transformed CRP (regression coefficient [beta]=-0.023, 95% CI -0.033 to -0.012) and IL-6 (beta=-0.025, 95% CI -0.049 to -0.001) were inversely associated with the ankle-arm index. Only CRP was associated with carotid intima-media thickness (beta=0.018, 95% CI 0.010 to 0.027). Compared with the lowest tertile, the odds ratio for moderate to severe carotid plaques associated with levels of CRP in the highest tertile was 2.0 (95% CI 1.3 to 3.0). Soluble intercellular adhesion molecule-1 levels were strongly associated with carotid plaques (odds ratio 2.5, 95% CI 1.5 to 4.4 [highest versus lowest tertile]). Soluble vascular cell adhesion molecule-1 was not significantly associated with any of the measures of atherosclerosis. This study indicates that CRP is associated with the severity of atherosclerosis measured at various sites. Associations of the other markers with atherosclerosis were less consistent. http://repub.eur.nl/res/pub/9739/ 2001-01-01T00:00:00Z Insulin resistance, which is highly prevalent in the elderly, is suggested to be accompanied by an increased acute phase response. Until now, it is unclear whether cellular adhesion molecules are involved in the clustering of insulin resistance. In the present study, we examined the relationship of insulin resistance (measured by postload insulin) with levels of markers of inflammation and cellular adhesion molecules in a random sample of 574 nondiabetic elderly men and women participating in the Rotterdam Study. Associations were assessed by regression analysis, with ln-insulin as the dependent variable [regression coefficient (95% confidence interval)]. In our population, insulin was strongly and significantly (P < 0.001) associated with the markers of inflammation C-reactive protein [1.52 (0.96-2.08)], alpha-1-antichymotrypsin [1.25 (0.82-1.69)], and IL-6 [2.60 (1.69-3.52)], adjusted for age and gender. Associations weakened, to some extent, after additional adjustment for measures of obesity, smoking, and cardiovascular disease. Insulin was associated with the soluble intercellular adhesion molecule 1 [2.22 (1.29-3.16; P < 0.001)], whereas no association with the soluble vascular cell adhesion molecule 1 was found. The strength of the associations of insulin with C-reactive protein, alpha-1-antichymotrypsin, IL-6, and soluble intercellular adhesion molecule 1, as assessed by standardized regression coefficients, was comparable with the strength of the associations of insulin with high-density lipoprotein cholesterol, body mass index, and waist-to-hip ratio. The results of this population-based study indicate that low-grade inflammation and the cellular adhesion molecule soluble intercellular adhesion molecule 1 are an integral part of insulin resistance in nondiabetic elderly. These factors may contribute to the well-known relationship between insulin resistance and cardiovascular disease risk and might potentially become therapeutic targets in insulin resistant subjects.