2022 Alzheimer's Association Research Grant to Promote Diversity (AARG-D)

Brain Imaging Mechanisms Associated with Psychosis in Alzheimer's Disease

 What biological brain changes are associated with psychotic symptoms (such as hallucinations and delusions) in Alzheimer’s?

Jesus Gomar, Ph.D.
Feinstein Institute for Medical Research
Manhasset, NY - United States

Background

Psychotic symptoms, such as hallucinations and delusions, affect about 40-60% of individuals with Alzheimer’s. Such symptoms are often associated with steeper cognitive and functional decline and hastened mortality, compared to Alzheimer’s without psychotic symptoms. Psychotic symptoms in Alzheimer’s are likely driven by disturbances impacting several brain regions. These symptoms may be associated with specific cognitive impairments and could involve social cognition, working memory, and executive functions (a group of mental processes that include controlling attention and regulating impulsive behavior).[HS1] [CMK2]  However, the underlying biology of psychotic symptoms associated with Alzheimer’s is not well understood.

The protein tau helps maintain the structure of brain cells. In Alzheimer’s and other brain diseases, the shape of tau protein becomes modified or “misfolded,” a change that may contribute to tau tangles (a hallmark of these diseases) and subsequent nerve cell damage. Dr. Jesus Gomar and colleagues have shown that individuals with Alzheimer’s with psychotic symptoms have increased tau tangles in their brains compared to individuals with Alzheimer’s without psychotic symptoms. The research team also found that the accelerated trajectory of cognitive impairment in individuals with Alzheimer’s with psychotic symptoms may be related to a more rapid accumulation of tau tangles, which disrupts brain networks involved in reasoning and perception.
 

Research Plan

Dr. Gomar and colleagues will use different brain imaging techniques to study the underlying biological mechanisms associated with psychotic symptoms in Alzheimer’s. They will recruit 20 individuals with Alzheimer’s with psychotic symptoms, 20 individuals with Alzheimer’s without psychotic symptoms, and 20 cognitively unimpaired individuals. First, the researchers will assess psychotic symptoms in all individuals. The team will then use various brain scan techniques to measure the amount of tau tangles in their brains. They will also assess the overall health of the brain networks, including its structure and how the brain connections are functioning in the individuals. Finally, the team will study the association between tau tangles and measures of structural and functional connectivity in specific brain networks between groups.

Impact

This study may shed light on the relationship between biological brain changes and certain psychotic symptoms that may occur in some individuals with Alzheimer’s, and open up new directions of research to develop possible therapies to help address these symptoms.