Mixed effects of perfluoroalkyl and polyfluoroalkyl substances exposure on cognitive function among people over 60 years old from NHANES

The relationship between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and cognitive function are inconsistent, and the mixed effects of PFAS on cognitive function are still unclear. We aimed to evaluate the joint effects of PFAS on cognitive function assessed using four tests as follows: the Consortium to Establish a Registry for Alzheimer's Disease Immediate Recall Test (IRT), Delayed Recall Test (DRT), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST) in the US elderly. A total of 777 individuals aged ≥ 60 from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were included in this study. Multivariable logistic regression and Bayesian kernel machine regression (BKMR) were constructed to estimate the overall and the individual effects of PFAS exposure on cognitive function. There were 21.36%, 22.65%, 21.62%, and 21.24% participants with cognitive decline in IRT, DRT, AFT, and DSST, respectively. After multivariable adjustment, perfluorooctanoic acid (PFOA) was inversely associated with cognitive decline in IRT, DRT, and AFT, while no significant association was observed between any other PFAS and cognitive decline. Compared with the lowest quartile, the adjusted odds ratio of cognitive decline with a 95% confidence interval (CI) for the highest quartile of PFOA was 0.33 (95% CI: 0.15-0.69) in IRT, 0.50 (0.26-0.96) in DRT, and 0.45 (0.21-0.95) in AFT. In BKMR analysis, the overall effect of mixtures was significantly protective on cognitive decline in IRT, of which PFOA made the greatest contribution. The consistent protective effect in DRT and DSST was observed when all the chemicals were at their 50th percentile or below it. No significant interaction was observed among PFAS for cognitive function. These findings suggested that PFAS mixture at a low level of current exposure of the US population may have a protective effect on cognitive function.