2022 Alzheimer's Association Research Fellowship (AARF)

A Noninvasive Assay of Entorhinal Grid-Coding in Mild Cognitive Impairment

What kind of brain cell activity is associated with difficulties in identifying a location or surroundings in older adults at risk for Alzheimer’s?

Paul Hill, Ph.D.
University of Arizona
Tucson, AZ - United States

Background

Studies show that a common early symptom of Alzheimer’s is spatial disorientation, the inability to recognize places and find one’s way from one location to another, even in familiar environments such as a neighborhood or home. Even in cognitively unimpaired older adults, spatial challenges may possibly be an early behavioral change associated with later onset of Alzheimer’s. 

While scientists do not know exactly how spatial disorientation develops in early Alzheimer’s, some studies suggest it may involve damage to certain cells in a region of the brain called the entorhinal cortex. The entorhinal cortex is crucial for memory formation and navigation. This is also one of the first brain regions impacted by the accumulation of the tau protein into tangles, one of the hallmark brain changes observed in Alzheimer’s as well as other brain diseases. Studies of genetically engineered Alzheimer’s-like mice have shown that tau tangles in the brain may cause dysfunction in certain cells in the entorhinal cortex, resulting in impaired spatial memory.
 

Research Plan

Dr. Paul Hill and colleagues will use specialized brain scanning methods and virtual reality experiments to study the spatial abilities of younger adults and older adults with and without mild cognitive impairment (MCI), a condition characterized by subtle memory loss that may precede Alzheimer’s. Participants will undergo a brain scan (functional magnetic resonance imaging or fMRI) while completing a navigation task in a virtual environment to detect changes in blood flow. The researchers will also measure the activity of nerve cells in the entorhinal cortex using a method called BOLD (blood oxygenation level dependent) imaging to visualize the changes in blood flow. Then, the research team will compare participants’ performances on cognitive tests for both object memory and spatial memory after the virtual task. Dr. Hill and colleagues will study whether age and/or cognitive status impacts the link between cellular activity in the entorhinal cortex and subsequent memory performance. 
 

Impact

The findings may help explain the biological underpinnings of impaired spatial abilities in older adults. If successful, the results of this study may inform future therapeutic strategies and interventions targeting spatial abilities in individuals at risk for Alzheimer’s.