Holly Hunsberger, PhD


Using "education" to enhance cognitive reserve



In the face of age-related changes, having cognitive reserve (CR) can buffer against neuropathology and cognitive stressors that often lead to degeneration. Brain maintenance, a compliment of CR, refers to the relative absence of change over time with age. Although there are many variables that affect CR, such as age, IQ, socioeconomic status (SES), and stress, higher levels of education are associated with a lower risk of dementia and widely used as an indicator of CR. These findings suggest that improving education can boost CR to act as a defense against dementia and age-related cognitive decline (ARCD). Therefore, it is essential to understand how environmental changes during aging impact CR on a behavioral and neural level. Many studies of CR have been performed using large human datasets, but this hinders our ability to look at brain changes on the cellular level. Longitudinal animal studies provide a great opportunity to gain further insight into the molecular mechanisms of CR’s impact on ARCD. For example, in the Tg2576 Alzheimer’s disease (AD) mouse model, environmental enrichment (EE) did not have long lasting effects on memory capacity as measured by EEG recordings. However, repeated cognitive stimulation using Morris water maze (MWM) training (heretofore considered a proxy for education) regime for 3 months improved memory performance of the 3xTg-AD mouse model. Despite these results, a majority of research has focused on EE alone and less on a more rigorous form of educational training in mice. Therefore, it is essential that we use education or training as a tool to assess CR in mice. 
 
Here, I propose a pilot study to examine how education affects CR in a novel mouse model. I will use our activity-dependent memory tagging system, the ArcCreERT2 x EYFP mice. These mice allow for brain-wide indelible labeling of neuronsactivated during learning, which then can be compared with secondary neuronal ensembles activated during memory retrieval. The neurons activated at both time points represent a memory trace or engram. By determining which areas of the brain are involved in maintaining or enhancing CR, we can better understand how to create lifestyle changes or therapeutic