Sung Kyun Park1, Ning Ding2, Dehua Han2. 1. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA; Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA. Electronic address: sungkyun@umich.edu. 2. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Abstract
BACKGROUND: Although potential neurotoxicity of perfluoroalkyl and polyfluoroalkyl substances (PFAS) is suggested, previous epidemiologic studies have reported a 'protective' association between serum PFAS concentration and cognition function. Poor outcome assessment, residual confounding, non-monotonic dose-responses (NMDRs), and the role of reduced kidney function in PFAS excretion may be alternative explanations of these findings. OBJECTIVES: We examined the association of perfluoroalkyls with cognitive functions assessed using the Consortium to Establish a Registry for Alzheimer's Disease word learning and recall; the Animal Fluency; and the Digit Symbol Substitution tests. METHODS: We included 903 adults aged ≥60 years from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. We computed a composite z-score as an average of four individual cognitive z-scores and used it as the outcome. Linear and generalized additive models were used to evaluate linear and non-linear associations. RESULTS: With the linearity assumption, perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) were significantly positively associated with composite z-score after adjustment for age, sex, race/ethnicity, education, smoking, poverty-income ratio, health insurance, food security, alcohol, and physical activity. Smoothing plots suggested NMDRs, especially for perfluorooctane sulfonate (PFOS) with a U-shape dose-response. When restricting to participants without chronic kidney disease (CKD) (n = 613), the positive associations for PFOA and PFNA observed in the whole population diminished, whereas PFOS was inversely and significantly associated with composite z-score. Also, negative confounding effects of fish/seafood consumption seem to be substantial. Effect estimates of composite z-score were -0.055 (95% CI: -0.097, -0.012, P = 0.01) for a doubling increase in PFOS. DISCUSSION: These findings suggest that the previous epidemiologic findings of a 'protective' association between PFAS and cognition may be explained by CKD, NMDRs and confounding by fish consumption. PFOS at the current population exposure level in the U.S. may be a risk factor for cognitive decline in older adults with normal kidney function.
BACKGROUND: Although potential neurotoxicity of perfluoroalkyl and polyfluoroalkyl substances (PFAS) is suggested, previous epidemiologic studies have reported a 'protective' association between serum PFAS concentration and cognition function. Poor outcome assessment, residual confounding, non-monotonic dose-responses (NMDRs), and the role of reduced kidney function in PFAS excretion may be alternative explanations of these findings. OBJECTIVES: We examined the association of perfluoroalkyls with cognitive functions assessed using the Consortium to Establish a Registry for Alzheimer's Disease word learning and recall; the Animal Fluency; and the Digit Symbol Substitution tests. METHODS: We included 903 adults aged ≥60 years from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. We computed a composite z-score as an average of four individual cognitive z-scores and used it as the outcome. Linear and generalized additive models were used to evaluate linear and non-linear associations. RESULTS: With the linearity assumption, perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) were significantly positively associated with composite z-score after adjustment for age, sex, race/ethnicity, education, smoking, poverty-income ratio, health insurance, food security, alcohol, and physical activity. Smoothing plots suggested NMDRs, especially for perfluorooctane sulfonate (PFOS) with a U-shape dose-response. When restricting to participants without chronic kidney disease (CKD) (n = 613), the positive associations for PFOA and PFNA observed in the whole population diminished, whereas PFOS was inversely and significantly associated with composite z-score. Also, negative confounding effects of fish/seafood consumption seem to be substantial. Effect estimates of composite z-score were -0.055 (95% CI: -0.097, -0.012, P = 0.01) for a doubling increase in PFOS. DISCUSSION: These findings suggest that the previous epidemiologic findings of a 'protective' association between PFAS and cognition may be explained by CKD, NMDRs and confounding by fish consumption. PFOS at the current population exposure level in the U.S. may be a risk factor for cognitive decline in older adults with normal kidney function.
Authors: Laura N Vandenberg; Theo Colborn; Tyrone B Hayes; Jerrold J Heindel; David R Jacobs; Duk-Hee Lee; Toshi Shioda; Ana M Soto; Frederick S vom Saal; Wade V Welshons; R Thomas Zoeller; John Peterson Myers Journal: Endocr Rev Date: 2012-03-14 Impact factor: 19.871
Authors: Konstantinos Prevedouros; Ian T Cousins; Robert C Buck; Stephen H Korzeniowski Journal: Environ Sci Technol Date: 2006-01-01 Impact factor: 9.028
Authors: Stephanie J Frisbee; Anoop Shankar; Sarah S Knox; Kyle Steenland; David A Savitz; Tony Fletcher; Alan M Ducatman Journal: Arch Pediatr Adolesc Med Date: 2010-09
Authors: Anne P Starling; Stephanie M Engel; Kristina W Whitworth; David B Richardson; Alison M Stuebe; Julie L Daniels; Line Småstuen Haug; Merete Eggesbø; Georg Becher; Azemira Sabaredzovic; Cathrine Thomsen; Ralph E Wilson; Gregory S Travlos; Jane A Hoppin; Donna D Baird; Matthew P Longnecker Journal: Environ Int Date: 2013-11-02 Impact factor: 9.621
Authors: Ning Ding; Siobán D Harlow; John F Randolph; Bhramar Mukherjee; Stuart Batterman; Ellen B Gold; Sung Kyun Park Journal: Am J Epidemiol Date: 2022-06-27 Impact factor: 5.363
Authors: Sung Kyun Park; Xin Wang; Ning Ding; Carrie A Karvonen-Gutierrez; Antonia M Calafat; William H Herman; Bhramar Mukherjee; Siobán D Harlow Journal: Diabetologia Date: 2022-04-11 Impact factor: 10.460
Authors: Tamara J Sussman; Brennan H Baker; Albert J Wakhloo; Virginie Gillet; Nadia Abdelouahab; Kevin Whittingstall; Jean-François Lepage; Lindsay St-Cyr; Amélie Boivin; Anthony Gagnon; Andrea A Baccarelli; Larissa Takser; Jonathan Posner Journal: Environ Res Date: 2021-12-22 Impact factor: 6.498