Urinary Tobacco-specific Nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and Cognitive Functioning in Older Adults: The National Health and Nutrition Examination Survey 2013-2014

Abstract

Abstract Introduction Tobacco and tobacco smoke contain a class of carcinogens called tobacco-specific nitrosamines. A metabolite of tobacco-specific nitrosamine is 4-(methylnitrosamino)-1-(3-pyridyl)-1-Butanol (NNAL). We aimed to examine the association between urinary tobacco-specific NNAL (free NNAL plus NNAL-glucuronide) and cognitive functioning among a nationally representative sample of U.S. older adults. Method A total of 1,673 older adults aged 60 and above from the National Health and Nutrition Examination Survey 2013–2014 were included. Urinary tobacco-specific NNAL was collected in mobile health centers and analyzed in the laboratory. Cognitive functioning was measured using the Consortium to Establish a Registry for Alzheimer’s Disease Word Learning subtest (CERAD-WL) immediate and delayed memory tests, the Animal Fluency test (AFT), and the Digit Symbol Substitution Test (DSST). Test-specific and global cognition z-scores were calculated based on means and standard deviations (SD) of the cognitive test scores. Multivariable linear regression models were constructed to examine the independent association between quantiles of urinary tobacco-specific NNAL (reference: the lowest quantile) and cognitive test-specific and global cognition z-scores controlling for age, race/ethnicity, education, depressive symptoms, smoking status, body mass index, prevalent coronary heart disease, stroke, and systolic blood pressure. Results About half of the participants (mean age 69.8 years, SD 6.8) were female (52.1%), non-Hispanic White (48.3%), and completed some college and above (49.7%). Multivariate linear regressions showed that higher quantiles of urinary tobacco-specific NNAL, compared with the lowest quantile, was significantly associated with lower AFT (beta [β] -0.16, 95% confidence interval [CI] -0.27, -0.04), DSST (β -0.25, 95% CI -0.35, -0.14), and global cognition (β -0.15, 95% CI -0.27, -0.04) z-scores controlling for the covariates. Conclusions Higher urinary tobacco-specific NNAL was associated with worse cognitive functioning in older adults. Prevention and reduction of active or passive exposure to tobacco in older adults may help protect their cognitive functioning.