Abstract
BACKGROUND: Recent findings showed serious consequences of latent T. gondii infection on the central nervous system, leading to psychiatric, immunological and cognitive impairments. However, little is known about the temporal dynamics of the latent T. gondii infection in respect to immunological and cognitive changes across the adult life span. The present study aims at evaluating the course of cognitive changes across the adult life span in relation to latent T. gondii infection and the interplay with proinflammatory cytokines leading to chronic inflammation as a potential origin of the cognitive decline in infected adults. METHODS: In a double-blinded cross-sectional design, data of 218 seropositive and 475 seronegative adults aged between 20 and 88 years were compared regarding crucial cognitive domains: processing speed, working memory, immediate and delayed memory, sustained attention, and executive functions. In a subsample of up to 300 participants, concentrations of proinflammatory cytokines IL-6, IL-8, IL-18, and TNF-α were analyzed to evaluate their interaction with T. gondii, and to determine whether the cytokines interact in their effects on cognition across the lifespan. RESULTS: The results showed an interaction between age and T. gondii status, with a decline in cognitive performance in infected, relative to non-infected, older individuals, and the reversed pattern in young to middle-aged adults. Specifically, this pattern was evident in working memory, immediate and delayed recall, as well as switching ability. Age was associated with increased levels of proinflammatory cytokines, and reduced concentration of T. gondii antibodies. IL-6, IL-8 and TNF-α levels were negatively associated with T. gondii antibody level and cognitive performance. Finally, T. gondii interacted with IL-6, IL-8 and TNF-α, predicting superior performance in immediate and delayed memory tasks in younger adults with high levels of T. gondii IgG antibodies and cytokines, whereas T. gondii IgG antibody and cytokine levels played less of a role for these functions in older age. CONCLUSION: The findings support a model of dynamically shifting effects of T. gondii and proinflammatory cytokines on the central nervous system and cognition with increasing age, suggesting positive effects of T. gondii infections in younger adults, and neuroinflammatory effects in older age presumably due to chronic inflammation. Given the high prevalence of latent toxoplasmosis in the general population and the growing population of older adults, these findings are of relevance for public health. TRIAL REGISTRATION: Clinicaltrials.gov NCT05155397.