Review: The Genetics of Delirium


The paper reviewed here is ‘The Role of Genetics in Delirium in the Elderly Patient’ by van Munster, Rooij and Korevaar. In the abstract van Munster and colleagues write that

Two important gaps in daily practice with delirium are the pathophysiological obscurity and the low recognition rates. Genetics offers the possibility to contribute knowledge to both of these gaps with its unique and diverse techniques

The authors give an overview of delirium in the introduction before going on to consider the syndrome of delirium. They consider the difficulties of diagnosis given the relatively short window of time which may be available to make the diagnosis as well as a number of other practical issues. The authors consider briefly and in turn several hypotheses about the aetiology of delirium including the dysregulation of dopamine or acetylcholine, the stress response and the immune response particularly the response involving cytokines. The authors then go on to consider the genotype and phenotype of delirium.

The authors hypothesise that if genetic risk factors are present, the precipitants for an episode can be ‘milder’. They also suggest that the study of the genetics of delirium is comparatively more difficult than with other diseases as the average age of onset of delirium may be causally related to the relative dearth of twin studies in this area. They then look at the methodology of genetic studies including the gene-wide association studies and look at some of the advantages comparing them with invasive procedures.

They use the broad categories describe above to suggest some suitable candidate genes which are listed in table 1. These can be compared with the genetic studies that have already been carried out and which are described in a later section. A number of the studies examining APOE4 associations for instance have not produced such interesting findings. The authors conclude with some suggestions of how future studies can facilitate a better understanding of the role of genetic factors in delirium including cohort studies.

I was persuaded by a number of the arguments particularly the suggested model combining precipitants with the genetic risk factors. While there is no explicitly stated methodology for the construction of the paper the authors have used a systematic approach towards the article which identifies a list of candidate genes as well as justifying an investigation into the genetics of delirium as well as highlighting potential difficulties of such an approach. This is a young field and articles such as this provide a useful overview.


van Munster B C, de Rooij S E and Korevaar J C. The role of genetics in delerium in the elderly patient. Dement Geriatr Cogn Disord. 2009. 28. 187-195.


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