Associations of Serum Cortisol with Cognitive Function and Dementia: The Rotterdam Study
Authors: Schrijvers, Elisabeth M.C. | Direk, Nese | Koudstaal, Peter J. | Kirschbaum, Clemens | Hofman, Albert | Tiemeier, Henning | Breteler, Monique M.B.
Article Type: Research Article
Abstract: 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. Show more
Keywords: Alzheimer's disease, cognition, cortisol, dementia
DOI: 10.3233/JAD-2011-110224
Citation: Journal of Alzheimer's Disease, vol. 25, no. 4, pp. 671-677, 2011
Association of HSP70 and its Co-Chaperones with Alzheimer's Disease
Authors: Broer, Linda | Ikram, Mohammad Arfan | Schuur, Maaike | DeStefano, Anita L. | Bis, Joshua C. | Liu, Fan | Rivadeneira, Fernando | Uitterlinden, Andre G. | Beiser, Alexa S. | Longstreth, William T. | Hofman, Albert | Aulchenko, Yurii | Seshadri, Sudha | Fitzpatrick, Annette L. | Oostra, Ben A. | Breteler, Monique M.B. | van Duijn, Cornelia M.
Article Type: Research Article
Abstract: The heat shock protein (HSP) 70 family has been implicated in the pathology of Alzheimer's disease (AD). In this study, we examined common genetic variations in the 80 genes encoding HSP70 and its co-chaperones. We conducted a study in a series of 462 patients and 5238 unaffected participants derived from the Rotterdam Study, a population-based study including 7983 persons aged 55 years and older. We genotyped a total of 12,053 Single Nucleotide Polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. Replication was performed in two independent cohort studies, the Framingham Heart study (FHS; n = 806) and Cardiovascular Health …Study (CHS; n = 2150). When adjusting for multiple testing, we found a small but consistent, though not significant effect of rs12118313 located 32 kb from PFDN2, with an OR of 1.19 (p-value from meta-analysis = 0.003). However this SNP was in the intron of another gene, suggesting it is unlikely this SNP reflects the effect of PFDN2. In a formal pathway analysis we found nominally significant evidence for an association of BAG, DNAJA and prefoldin with AD. These findings corroborate with those of a study of 2032 AD patients and 5328 controls, in which several members of the prefoldin family showed evidence for association to AD. Our study did not reveal evidence for a genetic variant if the HSP70 family with a major effect on AD. However, our findings of the single SNP analysis and pathway analysis suggest that multiple genetic variants in prefoldin are associated with AD. Show more
Keywords: Alzheimer's disease, genetic association studies, heat-shock proteins, prefoldin
DOI: 10.3233/JAD-2011-101560
Citation: Journal of Alzheimer's Disease, vol. 25, no. 1, pp. 93-102, 2011
