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2021 Alzheimer's Association Research Grant (AARG)

Linking Behavioral Instability and Latent State Dynamics in Alzheimer’s

Do changes in brain cell activity patterns impact cognition in Alzheimer’s?

Weidong Cai, Ph.D.
Stanford University
Redwood City, CA - United States



Background

Alzheimer’s is a progressive brain disease. Alzheimer’s can impact memory, thinking and behavior. Symptoms eventually may progress enough that may interfere with daily tasks. Studies show that variability in how a person behaves when asked to do the same task multiple times — known as “intra-individual response variability (IIRV)” may be associated with changes to attention and cognition observed in early stages of Alzheimer’s. Studies suggest that the IIRV may be associated with changes in brain cell activity patterns in early Alzheimer’s but this potential link has not been well understood.

Research Plan

For their project, Dr. Cai and colleagues will leverage the large scale Pittsburgh Connectomics in Brain Aging and Dementia study and use existing brain scans (functional Magnetic Resonance Imaging and Positron Emission Tomography) from participants. The participants include those with Alzheimer’s, individuals with mild cognitive impairment (a condition of subtle memory loss that may precede dementia, including Alzheimer’s dementia), and individuals who are cognitively unimpaired. Using the scans, the researchers will study nerve cell activity patterns in brain regions associated with attention and cognitive control (which is processing information and having the ability to adapt one’s behavior depending on current goals instead of being inflexible).

Further, Dr. Cai’s team will study the potential association between changes in brain activity patterns and different stages of Alzheimer’s as well as IIRV among the participants. The researchers will also investigate the association between changes in brain activity patterns and the levels of beta-amyloid plaques in the brain; the beta-amyloid protein accumulates to form plaques, one of the hallmark brain changes observed in Alzheimer’s. Finally, the researchers will use statistical techniques to study whether changes in brain activity patterns can be used to predict different stages of Alzheimer’s.

Impact

The results of this study may shed light on how changes in brain activity patterns may be associated with cognitive changes observed in Alzheimer’s. If successful, the results may also lead to the development of biological markers (or biomarkers) that can be used for early detection of Alzheimer’s and to track the progression of the disease over time. Families facing Alzheimer’s now and in future will benefit greatly from early detection, allowing for important care and planning. Furthermore, when we have new therapies, we will be in a better position to know who needs treatment at the earliest time point.  

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