Do Protein Levels and Brain Structure Impact Cognition in Alzheimer's Disease?

Nicole McKay, PhD Washington University, School of Medicine

Co-Principal Investigators

Tammie Benzinger, MD, PhD Washington University, School of Medicine


We aim to understand how levels of tau impact the integrity of our brain's pathways and potentially lead to a decline in attentional control and cognition in autosomal dominant Alzheimer disease.

Project Details

We are aiming to characterize attentional control in individuals with Autosomal Dominant Alzheimer disease (ADAD), allowing us to compare accuracy, reaction time, and variability in attentional control performance for those who carry the ADAD mutations to those who do not. We will also investigate how validated and novel measures of white matter integrity relate to these behavioral metrics. Finally, we will consider how the accumulation of the tau protein influences the relationship between these structures and cognition. 

By using both composite and variability metrics, we increase our sensitivity to detect subtle, early, cognitive change. Using data collected via the Dominantly Inherited Alzheimer Network, we can assess AD-specific pathology related to cognitive decline, in a population relatively free of age-related comorbidities. We utilize cognitive, neuroimaging, mass spectrometry, and fluid biomarker analyses, to build a comprehensive understanding of the influence these biomarkers have on preclinical cognitive decline. By extending prior work to include sensitive measures of attentional control and cognitive decline, we may be able to detect changes in cognition at an earlier time point than has been previously possible. This would be of particular importance to the general public as it may help to inform the design of future clinical trials or interventions aiming to improve the cognitive outcomes of individuals who are impacted by Alzheimer disease.