Modeling the impact of genotype, age, sex, and continuous navigation on pathway integration performance

The Path Integration (PI) task stands as a fundamental activity within spatial navigation, encompassing a multifaceted underlying process that requires extensive computation of both translational and directional information during navigation. This task is postulated to engage the entorhinal cortex (EC), a critical brain region. Although rodent studies have firmly linked the EC with the PI task, such a correlation has yet to be definitively established in humans. Individuals harboring high-risk genes associated with Alzheimer’s disease (AD) present a unique opportunity to explore PI task performance in humans because EC is the first targeted region during the pathological development of AD. Furthermore, the execution of the PI task is also susceptible to the influences of age and gender. In order to methodically probe the influences of various factors on PI performance, we conducted a PI task in a cohort characterized by high-risk AD-associated genes in a virtual island environment with surrounding landmarks. Our findings unveiled intricate interactions between these risk genes, age, and gender in shaping PI performance, an influence primarily mediated through distance and angle estimation. This study provides an illuminating perspective on the investigation into the functional role of the entorhinal cortex within the context of the PI task. ### Competing Interest Statement The authors have declared no competing interest.