The Role of Genetics in Delirium in the Elderly Patient

Munster, Barbara C. Van; Rooij, Sophia E. de; Korevaar, Johanna C.

doi:10.1159/000235796

Cited by 31 publications

(34 citation statements)

References 90 publications

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“…34 Previous observations suggest that inflammatory markers, especially the microglial markers CD68 and HLA-DR, show higher activity in two of the most important predisposing factors for delirium, i.e., higher age and cognitive impairment. 14,35 The question emerges whether this relationship between delirium and a higher level of inflammation in the brain can be attributed solely to the prior activation of microglia in the brain associated with these predisposing factors for delirium.…”

Section: Figmentioning

confidence: 99%

Neuroinflammation in Delirium: A Postmortem Case-Control Study

Munster

Aronica

Zwinderman

et al. 2011

Rejuvenation Research

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133

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Background: Delirium can be hypothesized to be an extreme manifestation of sickness behavior in elderly persons with neurodegenerative disease. The purpose of this study was to investigate whether increased cerebral inflammation with microglial, astrocyte, and cytokine activation exists in patients with delirium compared to nondelirious patients. Methods: Postmortem brain tissue from 9 cases with delirium was compared to 6 age-matched controls without delirium. Human leukocyte antigen-DR (HLA-DR) and CD68 cell count and glial fibrillary acidic protein (GFAP), interleukin-1b (IL-1b), IL-6,b-amyloid, and tau protein immunoreactivity were determined in hippocampus, frontal cortex, and white matter. Results: There were no significant differences in the patients with delirium compared to the controls with respect to age 73 versus 70.5 years ( p = 0.72) or dementia (22% versus 0%, p = 0.22). Both markers for microglial activity showed significantly higher scores in delirium brain specimens than controls in the total brain score (HLA-DR 129 vs. 20 and CD68 30 vs. 8.5) as well as in the various brain areas separately. The immunoreactivity of astrocyte activity (GFAP) was higher in the total brain score in patients with delirium (5.2 vs. 4.0, p = 0.05), but in the various brain areas this was only significant in the dentate gyrus. IL-6 immunoreactivity was higher in patients with delirium in all brain areas and IL-1b was not detectable. Coexisting infectious disease or dementia did not influence the overall results. Conclusions: These preliminary study results show an association between human brain activity of microglia, astrocytes, and IL-6 and delirium in elderly patients and add to the accumulating evidence that inflammatory mechanisms are involved in delirium.

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Section: Figmentioning

confidence: 99%

Neuroinflammation in Delirium: A Postmortem Case-Control Study

Munster

Aronica

Zwinderman

et al. 2011

Rejuvenation Research

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133

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“…Furthermore, we selected these five SNPs because they have been found before in studies in association with diseases, which makes functionality probable. However, we have not investigated the entire gene, so we could have missed certain (unknown) SNPs that are associated with delirium [40].…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the Melatonin Receptor 1B Gene and the Risk of Delirium

Jonghe¹,

Rooij²,

Tanck

et al. 2012

Dement Geriatr Cogn Disord

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Background/Aims: A disturbed sleep-wake rhythm cycle can be seen in delirium and as melatonin regulates this cycle via melatonin receptors, genetic variations in these receptors may contribute to susceptibility to delirium. The purpose of this study was to investigate whether genetic variants in the melatonin receptor 1B (MTNR1B) gene are associated with delirium. Methods: Elderly medical and hip surgery patients were included in the study. Five single-nucleotide polymorphisms (SNPs) were determined in the MTNR1B gene, i.e. rs18030962, rs3781638, rs10830963, rs156244 and rs4753426. Results: In total, 53% of 171 hip fracture patients and 33% of 699 medical patients were diagnosed with delirium. None of the polymorphisms were found to be associated with the occurrence of delirium. Conclusion: Future research could focus on sequencing this gene to look for other functional SNPs in relation to delirium.

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“…Additionally, the utilization of a haplotype analysis including other candidate genes to assess functional synergistic effects could be promising [28]. However, genetic research in delirium is only starting and large cohorts for reliable validation are not yet available [10]. …”

Section: Discussionmentioning

confidence: 99%

“…Genetic studies into dopamine-related genes in delirium in elderly patients are scarce, although these studies could offer a promising contribution to the knowledge of the pathophysiology [10]. Former studies showed that the SLC6A3 gene (rs393795) and possibly the DRD2 gene (rs6276) were associated with delirium [11].…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the Catechol-O-Methyltransferase Gene and Delirium in the Elderly

Munster¹,

Baas

Tanck

et al. 2011

Dement Geriatr Cogn Disord

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Background/Aims: Catechol-O-methyltransferase, encoded by the COMT gene, is one of the enzymes that degrade dopamine. The aim of this study was to investigate whether polymorphisms in the COMT gene were associated with delirium. Methods: Patients aged 65 years and older, acutely admitted to the medical department or to the surgical department following hip fracture, were included. rs4680, rs4818, and rs6269 were genotyped. Results: Delirious patients were older, and more frequently had preexisting functional or cognitive impairment (p < 0.001). Polymorphisms in the COMT gene were not associated with the development of delirium. Conclusion: Although the COMT gene is a promising candidate gene for delirium in the elderly, functional genetic variations were not associated with delirium.

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The Role of Genetics in Delirium in the Elderly Patient

Cited by 31 publications

References 90 publications

Neuroinflammation in Delirium: A Postmortem Case-Control Study

Neuroinflammation in Delirium: A Postmortem Case-Control Study

Polymorphisms in the Melatonin Receptor 1B Gene and the Risk of Delirium

Polymorphisms in the Catechol-O-Methyltransferase Gene and Delirium in the Elderly

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