It’s a beer, a video game, a Cirque du Soleil show, a song by Prince—people seem to have a heady relationship with the mental state called delirium. It may have even inspired the best of Guy de Maupassant. But as the French author’s writings attest, delirium is a serious medical condition. It may also be a harbinger of rapid decline in AD patients, according to a paper in the May 5 issue of Neurology. Researchers led by Tamara Fong at Beth Israel Deaconess Medical Center, Boston, report that the rate of cognitive decline accelerates in AD patients following a single episode of delirium. “I think this is an important study and provides a unique insight into the interaction between Alzheimer's and a common medical condition, delirium,” David Knopman, Mayo Clinic, Rochester, Minnesota, told ARF via e-mail. Knopman is an associate editor of Neurology. “I think the study will help physicians better understand the interplay of these two conditions,” he added. The finding also suggests that preventing the syndrome may help slow cognitive decline in some patients.

Delirium can be brought on by a variety of medical disorders or complications, including infection, surgery, and adverse reaction to medication. It goes under the names acute confusional state, acute brain syndrome, or toxic-metabolic encephalopathy. For the purpose of their study, Fong and colleagues considered all these the same syndrome and lumped them together under the term “acute brain failure.” Using data from the patient registry of the Massachusetts Alzheimer’s Disease Research Center, Fong and colleagues identified 112 AD patients who had been hospitalized and had a diagnosis that fell under the acute brain failure umbrella. For 72 of them, the delirium occurred between their second and third routine cognitive assessment, and the researchers used data from those patients to determine how it affected the trajectory of their cognitive decline. In comparison to 336 AD controls, patients with a delirium diagnosis had a statistically greater decline between the second and third cognitive assessment, as judged by the Information-Memory-Concentration (IMC) subtest of the Blessed Dementia Rating Scale. Patients who had an episode of delirium slid 4.9 points per year on this scale, compared with 2.5 points per year for patients without delirium. Decline on the scale was 2.5 points per year for patients without, but 4.9 points per year in those with, an episode of delirium.

The authors write that replication of this study is needed. If the finding holds up, then treating or preventing delirium might help slow disease progression in AD patients. The authors note that the work is a proof of concept for an observation clinicians commonly make in daily practice, namely that “older patients—particularly those with dementia—may decline at a faster rate or never fully recover their cognitive function following an episode of delirium.” Knopman told ARF that delirium is almost always treated but that there is no specific drug for the condition, and that prevention is a key issue. Identifying people at risk when they enter the hospital, then as much as possible avoiding known risk factors for delirium, such as sedation, could be helpful, he suggested. “Ultimately, the information derived from this study provides the foundation for future randomized intervention studies to determine whether preventions of delirium might ameliorate and/or delay cognitive decline in patients with AD,” wrote Fong and colleagues.—Tom Fagan


  1. This retrospective analysis indicates that episodes of delirium are associated with an increased rate of disease progression in dementia. This is one of the few factors shown to influence rate of disease progression. Delirium is a syndrome with multiple underlying mechanisms to the specific mechanism responsible for acceleration of AD progression is uncertain. More information about the nature of the delirium might suggest brain abnormalities leading to rapid AD progression and vulnerability to delirium.

    View all comments by Richard C. Mohs
  2. Post-anesthesia delirium has long been noted to be related to significant cognitive decline in the elderly. I am thrilled to see exploration of this phenomenon. It is devastating that a simple, medically necessary surgery leads so many on a downward spiral from which they never recover. I hope this eventually leads to the development of anesthesia drugs that are less likely to contribute to this rapid decline.

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External Citations

  1. beer
  2. French author’s writings

Further Reading

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Primary Papers

  1. . Delirium accelerates cognitive decline in Alzheimer disease. Neurology. 2009 May 5;72(18):1570-5. PubMed.