Association between blood metals mixtures concentrations and cognitive performance, and effect modification by diet in older US adults

Abstract

Background: Chronic exposure to heavy metals has been associated with adverse neurological outcomes in older adults. Inflammatory processes are suspected as an underlying pathway by which metals exert their neurotoxicity. In parallel, a diet rich in antioxidant and anti-inflammatory components may protect against chronic inflammation.

Objectives: We examined the associations of blood concentrations of lead, cadmium, and manganese as a mixture with cognitive performance in older US adults and potential modification of these associations by diet as measured by the Healthy Eating Index 2015 (HEI-2015) and the Adapted Dietary Inflammatory Index (ADII).

Methods: We used data on 1,777 adults ≥60 years old from the US National Health and Nutrition Examination Survey (NHANES; 2011-2014). We derived the ADII and the HEI-2015 from two nonconsecutive 24-hour diet recalls. Cognitive performance was measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning subtest, the animal fluency test, and the Digit Symbol Substitution Test (DSST). We also constructed a composite z-score reflecting overall cognitive performance. We used quantile g-computation to evaluate the joint associations of a mixture of metals with cognitive performance test scores. We also evaluated effect modification by sex and diet quality indices using Cochran Q tests.

Results: The median (interquartile range) of blood metals were 0.38 μg/L (0.35), 14.70 μg/L (11.70), and 8.74 μg/L (4.06) for cadmium, lead, and manganese, respectively. Increasing blood concentrations of all metals by one quartile was associated with a decrease in overall cognitive performance (-0.04; 95% confidence interval [CI] = -0.09, 0.02), CERAD (-0.04; 95% CI = -0.12, 0.03), animal fluency (-0.02; 95% CI, -0.11, 0.06), and DSST (-0.05; 95% CI = -0.11, 0.02) test scores. These associations were more pronounced in adults with high pro-inflammatory or low-diet quality and null or positive though imprecise associations in participants with a high anti-inflammatory. These associations also varied by sex with inverse associations in men and positive associations in women.

Conclusions: Our findings suggest that adherence to an antioxidant and anti-inflammatory diet may prevent blood metals adverse cognitive effects among older adults. If confirmed, strategies based on diet could provide a potential complementary and efficient approach to counteract effects of environmental pollutants.

Keywords: Adapted Dietary Inflammatory Index; Cadmium; Epidemiology; Healthy Eating Index; Lead; Manganese; National Health and Nutrition Examination Survey.

Figure 1.

Overall and sex-specific adjusted beta coefficients (95% CI) for the overall cognitive function score and the specific cognitive performance tests, for increase in all blood metals by one quartile, NHANES 2011–2014. Model was adjusted for age (years), gender (except for stratified analysis on this variable), race/ethnicity (Mexican American, other Hispanic, Non-Hispanic White, Non-Hispanic Black, other race), language of the sample person interview instrument (English, Spanish), educational level (less than high school, high school, higher than high school), smoking status, marital status, poverty to income ratio (quartiles), and healthy eating index.

Figure 2.

Estimates (95% CI) of the associations of a one quartile increase in the metal mixture and overall cognitive function score and specific cognitive performance tests, by sex and ADII score, NHANES 2011–2014. Model was adjusted for age (years), race/ethnicity (Mexican American, other Hispanic, Non-Hispanic White, Non-Hispanic Black, other race), language of the sample person interview instrument (English, Spanish), educational level (less than high school, high school, higher than high school), smoking status, marital status, poverty to income ratio (quartiles), and healthy eating index. All P values for between ADII quartile tests of heterogeneity were >0.10 except for men (P of heterogeneity: 0.09 and 0.07 for the overall cognitive test and the animal fluency test scores, respectively).

Figure 3.

Estimates (95% CI) of the associations of a one quartile increase in the metal mixture and overall cognitive function score and specific cognitive performance tests, by Sex and HEI-2015, NHANES 2011–2014. Model was adjusted for age (years), race/ethnicity (Mexican American, other Hispanic, Non-Hispanic White, Non-Hispanic Black, other race), language of the sample person interview instrument (English, Spanish), educational level (less than high school, high school, higher than high school), smoking status, marital status, poverty to income ratio (quartiles), and ADII. All P values for between the HEI quartile tests of heterogeneity were >0.10 except for the overall cognitive test, the animal fluency test, and the CERAD test scores in women (all P of heterogeneity < 0.05) and the animal fluency test score in men (P of heterogeneity = 0.03).