This blog post delves into the observations of sex differences in cognitive function in older rodent models, exploring the factors that contribute to these disparities and their implications for our understanding of aging in humans. It is likely that men and women experience cognitive aging differently. While the exact reasons are complex and multifaceted, several key factors contribute to these variations.

• Hormones: Hormones play a pivotal role in cognitive aging. Estrogen has neuroprotective properties that may delay cognitive decline whereas testosterone may also influence cognitive function in other manners.
• Neuroinflammation and Immunity: Sex differences in the immune system activation and neuroinflammation may alter cognitive functioning with advanced age. The female immune system is more robust, which may beneficially reduce risk for neurodegenerative diseases.

However, there are challenges in this field considering that women tend to develop Alzheimer’s more frequently and often suffer a more substantial disease burden upon diagnosis. Further, numerous interactions between genetics, hormones, and the environment may also influence cognitive function with advanced age. As a result, our most recent study examining the cognitive impacts of loss of normal presenilin 2 function affords an innovative way to evaluate how repeated network hyperexcitability may negatively influence disease trajectory in a mouse model of Alzheimer’s disease-related genetic mutations. By examining how biological sex influences a protein known to be co-expressed with factors of the immune response and, subsequently, cognitive function, we gain valuable insights into the multifaceted nature of aging.