Dataset Information

Perfluoroalkyl substances and cognitive function in older adults: Should we consider non-monotonic dose-responses and chronic kidney disease?

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.

SUBMITTER: Park SK

PROVIDER: S-EPMC7736478 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPer- and polyfluoroalkyl substances (PFAS) are widely applied in consumer and industrial products such as nonstick cookware, waterproof clothing, food packaging materials, and fire-fighting foams. These "forever chemicals" are hypothesized to impact neurobehavioral functions. Yet no previous study has explored the role of PFAS on audiometrically determined hearing impairment (HI).ObjectivesTo investigate the associations of serum concentrations of perfluoroalkyl substances with low-frequency HI (LFHI) and high-frequency HI (HFHI) in US adults.MethodsWe evaluated the cross-sectional associations in 2371 adults aged 20-69 years who participated in the National Health and Nutrition Examination Survey (NHANES) 2003-2004, 2011-2012 and 2015-2016; and 449 adults aged ≥70 years from NHANES 2005-2006 and 2009-2010. Serum concentrations of perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA), were measured using solid-phase extraction coupled to High Performance Liquid Chromatography-Turbo Ion Spray ionization-tandem Mass Spectrometry. LFHI was defined as a pure-tone average (PTA) of thresholds across 0.5-1-2 kHz >25 dB; HFHI defined as a PTA across 3-4-6 kHz >25 dB in the worse ear. Survey-weighted logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) with adjustment for age, age-squared, sex, race/ethnicity, education, poverty-to-income ratio, body mass index, smoking status, exposures to occupational, recreational and firearm noises, and NHANES cycles.ResultsThere were no significant associations when perfluoroalkyl variables were fitted as a linear (log-transformed) term. However, statistically significant associations of HFHI with PFNA (OR = 1.70, 95% CI: 1.13-2.56) and PFDA (OR = 1.75, 95% CI: 1.00-3.05) were observed when comparing participants with serum concentrations ≥90th vs. <90th percentiles of PFNA (90th percentile = 1.8 ng/mL) and PFDA (90th percentile = 0.5 ng/mL), respectively, in adults aged 20-69 years. No significant associations were observed for other compounds in adults aged 20-69 years and for all compounds in adults ≥70 years.ConclusionsOur study does not provide strong evidence to support the ototoxicity of PFAS exposure. Non-linear threshold dose-response associations between serum concentrations of PFNA and PFDA and HFHI need further investigation.