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2018 Alzheimer's Association Research Fellowship (AARF)

Genetic and Inflammatory Mechanisms of Delirium and Alzheimer's Disease

How might stress-related delirium after surgery, increase risk for Alzheimer’s ?

Sarinnapha M. Vasunilashorn, Ph.D.
Beth Israel Deaconess Medical Center
Boston, MA - United States


Delirium disrupts mental abilities resulting in confusion and a decreased awareness of one's environment. Older people often experience delirium after surgery and other periods of acute stress, and those with Alzheimer's are at an especially high risk for the condition. In addition, current research suggests that delirium may hasten the progress of cognitive decline in the brain, and it may even place healthy people at greater risk for the disease. However the biological mechanisms linking delirium and Alzheimer's are as yet unknown and scientists believe that inflammation in the brain may play a role in these conditions. Based on previous findings, Dr. Sarinnapha M. Vasunilashorn and colleagues hypothesize that during moments of acute stress, immune system proteins in the brain can become activated and produce abnormal inflammation. This inflammation may lead to delirium and, ultimately, to the brain cell death associated with Alzheimer's. Moreover, as not all people with high inflammation develop delirium or Alzheimer's, Dr. Vasunilashorn posits that the link could be more common in those with certain genes that promote dementia risk.

Research Plan

Dr. Vasunilashorn and colleagues will test their hypothesis by analyzing medical data from two studies of older adults without dementia, who have undergone surgery. First, they will look for measures of biological changes (or biomarkers) in the participants' blood and cerebrospinal fluid (the fluid surrounding the brain) that indicate levels of brain inflammation and brain cell damage. They will then determine whether these biomarkers were linked to post-operative delirium. Lastly, the researchers will determine whether individuals with two genes thought to increase an individual's risk — APOE-e4 or abnormal catechol-o-methyltransferase (COMT) — might be more susceptible to delirium and dementia-related brain changes after surgery.


The results of this study will clarify our understanding of how delirium and other responses to acute stress could underscore a potential link to cognitive decline seen in Alzheimer's. It could also lead to delirium-preventing therapies that may prevent Alzheimer's or slow its progression.

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