Non-pathological decline in memory is a pervasive process during aging. One common age-associated condition that is linked to cognitive dysfunction is inflammation. In particular, cellular signaling via the nuclear factor kappa B pathway (NFκB), which regulates inflammation, is up-regulated during the aging process but its precise role in learning and memory across the lifespan is not fully understood. The purpose of the experiments in this dissertation were to investigate the role of NFκB in age-associated cognitive decline and to determine factors that mediate cognitive decline during aging in conditions with up-regulated NFκB signaling. To achieve these aims, young, middle-aged and aged rats were tested on a hippocampus-dependent memory task and levels of NFκB were compared between age groups and individual differences in NFκB levels were correlated with memory. In young mice, inflammation was induced via dextran sulfate sodium, and levels of NFκB and memory were compared between groups and individual variation in NFκB was correlated with behavior. Lastly, using the Midlife Development in the United States data set, the psychosocial variables that predict cognitive decline with age were examined in relation to inflammatory status. The results from this dissertation provide insight into the co-variation of NFκB signaling and cognition across the lifespan and identify important personal and experiential factors that may alter this relationship.