USF Health team gets $3.48M National Institute on Aging grant to study link between hospital-acquired delirium and the risk or progression of dementia

Researchers will focus on tau pathology in a mouse model to elucidate underlying causes.

Delirium is a serious form of mental impairment affecting 11 to 42 percent of elderly inpatients, particularly those hospitalized with infections, admitted to intensive care, or requiring surgery. The condition, marked by sudden-onset confusion and incoherence, is often underdiagnosed and can lead to devastating long-term health consequences.

Now, researchers at the University of South Florida have been awarded a five-year, $3.48 million grant from the National Institute on Aging (NIA) to investigate the observation that older adults who experience delirium while hospitalized can have higher risk afterwards of developing dementia.  They will also attempt to explain why the condition accelerates decline in patients who already have dementia.

The award titled “Influence of systemic immune inflammation upon the tauopathy phenotype in mouse models” will focus on tao pathology in a mouse model. Tau is one of the proteins that accumulates in Alzheimer’s brain tissue and is thought to cause the death of neurons. The grant was in response to a specific request from NIA for proposals forged by interdisciplinary investigative teams to address this question.

“The ultimate goal of this project is to identify the factors associated with general illness that impact Alzheimer’s pathology in the brain and block the influence of those factors on tau pathology, thus decreasing the risk or progression of dementia in individuals who develop general illnesses.” said principal investigator David Morgan, PhD, CEO of the USF Health Byrd Alzheimer’s Institute.

Dr. David Morgan.

Dr. David Morgan.

“It is testimony to the breadth of expertise at USF that we were able to assemble this team of experts to tackle this very complex problem and compete successfully with other universities.”

Joining Dr. Morgan on the study are co-investigators from the USF Health Morsani College of Medicine and the USF College of Pharmacy: Paula Bickford, PhD, professor at the USF Center of Excellence for Aging and Brain Repair; Chuanhai Cao, PhD, associate professor of pharmaceutical science; Marcia Gordon, PhD, professor of molecular pharmacology and physiology; Daniel Lee, PhD, assistant professor of pharmaceutical science; Kevin Nash, PhD, assistant professor of molecular pharmacology and physiology; Maj-Linda Selenica, PhD, assistant professor of pharmaceutical science; and Ken Ugen, PhD, professor of molecular medicine.

This investigative team combines expertise in Alzheimer’s disease, aging brain function, innate immunity and adaptive immunology to unravel the mechanisms by which general illness can increase risk and progression of dementia.

The researchers suspect that hospitalization and immune activation may feed back onto the brain to speed up Alzheimer’s pathology, Dr. Morgan said. “However, like all epidemiology, it could be reverse causality.  That is, those with existing Alzheimer’s pathology may be more prone to delirium with major infectious illness.  The studies we do in mice will help determine what the direction is.”