Perfluoroalkyl Substances and Cognitive Function in Older Adults: Should We Consider Non-Monotonic Dose-Responses and Chronic Kidney Disease?

Details

• Alternative Title:
  Environ Res
• Personal Author:
  Park, Sung Kyun ; Ding, Ning ; Han, Dehua
• Description:
  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.
  
  
• Subjects:
  Alkanesulfonic Acids Animals Article Caprylates Cognition Environmental Pollutants Fishes Fluorocarbons Nutrition Surveys Renal Insufficiency, Chronic
• Source:
  Environ Res. 192:110346
• Pubmed ID:
  33068581
• Pubmed Central ID:
  PMC7736478
• Document Type:
  Journal Article
• Funding:
  T42 OH008455/OH/NIOSH CDC HHSUnited States/ ; T42OH008455/ACL/ACL HHSUnited States/ ; P30 ES017885/ES/NIEHS NIH HHSUnited States/ ; R01 ES026578/ES/NIEHS NIH HHSUnited States/ ; P30 DK020572/DK/NIDDK NIH HHSUnited States/ ; R01 ES026964/ES/NIEHS NIH HHSUnited States/
• Volume:
  192
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:35bc393eeadc7a4ee442ade947aba4df44b597022142b9a688b6d648b22b9c97
• Download URL:
  https://stacks.cdc.gov/view/cdc/98839/cdc_98839_DS1.pdf
• File Type:
  [PDF - 564.71 KB ]