http://repub.eur.nl/res/aut/27940/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/30887/ 2011-09-21T00:00:00Z Higher levels of cortisol have been observed in persons with cognitive decline and dementia. It is unknown whether these higher levels are a cause or a consequence of disease. We investigated whether morning levels of serum cortisol were associated with cognitive function, cognitive decline, and the risk of dementia and Alzheimer's disease in the Rotterdam Study, a large prospective population based cohort study. Cortisol levels were assessed in fasting blood serum in 3341 participants, who were free of dementia at baseline (1997-1999). Cognitive function was assessed with a dedicated neuropsychological test battery at baseline and at follow-up examination (2002-2004). In addition, the cohort was continuously monitored for incident dementia until January 1, 2007. After a mean follow-up of 7.1 years, 243 participants had developed dementia, of whom 210 were diagnosed with Alzheimer's disease. Morning serum levels of cortisol were neither related to cognitive function at baseline, nor to annual cognitive decline. There was no relation between serum levels of cortisol and the risk of developing dementia or Alzheimer's disease. These results suggest that that morning serum cortisol is not a causal factor in the development of dementia. http://repub.eur.nl/res/pub/33683/ 2011-05-01T00:00:00Z We investigated concurrent as well as long-term effects of smoking on cortisol. The population consisted of 2508 elderly adults. Current smokers, as opposed to former smokers, had higher basal cortisol levels and higher morning increases of cortisol. Overall, pack-years was related to morning cortisol rise, but this was accounted for by current smokers. Time since quitting was positively associated with a greater decline in daytime cortisol indicating that the effects of smoking remit. This suggests that smoking has short-term, rather than long-term, consequences on cortisol secretion patterns. http://repub.eur.nl/res/pub/22822/ 2011-02-14T00:00:00Z Background: Depressive patients often have altered cortisol secretion, but few studies have investigated genetic variants in relation to both cortisol secretion and depression. To identify genes related to both these conditions, we: (1) tested the association of single nucleotide polymorphisms (SNPs) in hypothalamic-pituitary-adrenal-axis (HPA-axis) candidate genes with a summary measure of total cortisol secretion during the day (cortisolAUC), (2) performed a genome wide association study (GWAS) of cortisolAUC, and (3) tested the association of identified cortisol-related SNPs with depressive symptoms. Methods: We analyzed data on candidate SNPs for the HPA-axis, genome-wide scans, cortisol secretion (n = 1711) and depressive symptoms (the Centre for Epidemiology Studies Depression Scale, CES-D) (n = 2928) in elderly persons of the Rotterdam Study. We used data from the Whitehall II study (n = 2836) to replicate the GWAS findings. Results: Of the 1456 SNPs in 33 candidate genes, minor alleles of 4 SNPs (rs9470080, rs9394309, rs7748266 and rs1360780) in the FKBP5 gene were associated with a decreased cortisolAUC (p < 1 × 10(-4) after correction for multiple testing using permutations). These SNPs were also associated with an increased risk of depressive symptoms (rs9470080: OR 1.19 (95%CI 1.0; 1.4)). The GWAS for cortisol yielded 2 SNPs with p-values of 1 × 10(-06) (rs8062512, rs2252459), but these associations could not be replicated. Conclusions: These results suggest that variation in the FKBP5 gene is associated with both cortisolAUC and the likelihood of depressive symptoms.